Clinical Teaching Tool (CTT) HOSPICE PALLIATIVE CARE PROGRAM SYMPTOM GUIDELINES 2ND EDITION Final Draft endorsed by NH Medical Advisory Committee Date: October 2008 Reorder #1598 nd Hospice Palliative Care Symptom Guidelines 2 Edition Copyright © Northern Health Authority 2008 The Northern Health Authority (“NHA”) authorizes the use, reproduction and/or modification of this publication for purposes other than commercial redistribution. In consideration for this authorization, the user agrees that any unmodified reproduction of this publication shall retain all copyright and proprietary notices. If the user modifies the content of this publication, all NHA copyright notices shall be removed, however NHA and its source authors shall be acknowledged. Reproduction or storage of this publication in any form by any means for the purpose of commercial redistribution is strictly prohibited. While care has been taken to ensure the accuracy of the information contained in this publication as of the date of publication, the Northern Health Authority makes no warranty, express or implied, as to accuracy, completeness or currency. New knowledge, new technologies, clinical and research data, and clinical experiences may provide sound reasons for adopting alternative clinical practices. The ultimate judgment regarding the propriety of any specific clinical practice must be made by the health professional in light of the circumstances presented by the patient. Northern Health 11100 13th Street Dawson Creek, BC V1G 3W8 2507847338 Ext. 2490 www.northernhealth.ca Document1 Page 2 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table of Contents Acknowledgements ......................................................................................................... 4 The Authors..................................................................................................................... 5 Introduction ..................................................................................................................... 7 Symptom Assessment Acronym.................................................................................... 11 Amyotrophic Lateral Sclerosis (ALS)............................................................................. 13 Ascites........................................................................................................................... 21 Bowel Care.................................................................................................................... 26 Example of HPC Bowel Protocol .............................................................................. 35 Cough............................................................................................................................ 36 Dehydration................................................................................................................... 41 Delerium/Restlessness.................................................................................................. 48 Depression ............................................................................................................................. 56 Dyspnea ........................................................................................................................ 64 NH Home Oxygen Information .................................................................................. 72 Shortness of Breath Patient Handout ........................................................................ 73 Exsanguination.............................................................................................................. 75 Fatigue .......................................................................................................................... 79 PPS (Palliative Performance Scale) .......................................................................... 85 ECOG Performance Status ....................................................................................... 88 Hiccups ......................................................................................................................... 89 Hypercalcemia in Malignant Disease (Palliative Management) ..................................... 91 Lymphoedema .............................................................................................................. 98 Malignant Bowel Obstruction......................................................................................... 99 Nausea and Vomiting .................................................................................................. 105 N&V Pathway and Antiemetic Chart........................................................................ 112 Nutrition & Cachexia.................................................................................................... 113 Principles Of Pain Assessment ................................................................................... 119 Principles Of Pain Management .................................................................................. 124 Fentanyl Transdermal.............................................................................................. 144 Methadone............................................................................................................... 149 Tramadol ................................................................................................................. 161 Incident Pain............................................................................................................ 165 Respiratory Secretions / Congestion ........................................................................... 167 Palliative Sedation....................................................................................................... 172 Psychosocial care ....................................................................................................... 173 Spinal Cord Compression ........................................................................................... 174 Spiritual care ............................................................................................................... 181 Superior vena cava obstruction................................................................................... 182 Twitching / Myoclonus / Seizures ................................................................................ 183 INDEX ......................................................................................................................... 191 Document1 Page 3 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition ACKNOWLEDGEMENTS First and foremost we would like to thank the authors of the source publication – Fraser Health Hospice th Palliative Care Symptom Guidelines, 4 edition. We sincerely appreciate the huge amount of time and effort that Fraser Health has put into completing their superb evidence based set of guidelines. By allowing us to share their great work they have proven themselves to be true leaders in the field of palliative care. The guidance and support that we have received over the last two years from many professionals from Fraser Health including Bruce Kennedy, Barbara McLeod, and Carolyn Tayler as well as Dr. Pippa Hawley from the B.C. Cancer Agency, is greatly appreciated and will not be forgotten. “Leadership is practiced not so much in words as in attitude and in actions.” Harold Geneen In addition, we wish to acknowledge and thank the following people for their contributions in the publication of the 2nd edition of the Hospice Palliative Care Symptom Guidelines: Kath Murray and Dr. Michael Downing for offering their valued expertise and suggestions. Mary HendersonBetkus and Tim Rowe for helping to guide this project and assist with troubleshooting whenever we needed it. Barbara Hesse for her expertise in formatting and willingness to assist as technical challenges arose. Janice Reynolds for lending an extra hand and eye with the editing. She is an experienced pharmacist with a dedication to palliative care in Quesnel and we value her willingness to look outside of the box and extend her expertise even when it is not expected of her. Darcee Bidgood and her colleagues from the Vancouver Island Health Authority palliative team for offering to review and collaborate on implementation strategies. Bev Spring and her colleagues from the Vancouver Coastal Health palliative care team as well as Victoria Hospice for offering some of their most useful charts. The entire NH HPC Consult Team – Sandi Armitage, Cathy Czechmeister, Judy Lett, Lynn Shervill, Joan Patriquin, Elaine Minifie, Melinda Allison, Dr. Steve Ashwell, Dr. Inban Reddy, and Dr. Biz Bastian, not just for helping with the editing but also for the passion they have shown in developing and implementing a sustainable palliative care program within a region of vast geographical distances and human resource inconsistencies. The challenges that they have faced and the perseverance they have shown is truly remarkable. Nicole Dahlen Northern Health Hospice Palliative Care Pharmacist Lead Project Coordinator, Second Edition Hospice Palliative Care Symptom Guidelines October 2008 Document1 Page 4 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition THE AUTHORS NH Palliative Symptom Guidelines 2 nd Edition (October 2008) The Source Publication: Fraser Health Hospice Palliative Care Program Symptom Guidelines – Fourth Edition Layout Shervin Communications Inc. Reviewers Doris Barwich, MD, CCFP, Medical Leader, Hospice Palliative and End of Life Care, Northern Health , BC Pippa Hawley, B.Med, FRCPC, Palliative Medicine Specialist, BC Cancer Agency Bruce Kennedy, BSc.(Pharm.), M.B.A. Clinical Pharmacy Specialist Palliative Care, Northern Health , BC B. Lynn Kobierski, MD, CCFP, FCFP, Hospice Palliative Care Physician, Northern Health , BC Barbara McLeod, RN, BSN, MSN, CHPCN(C) Clinical Nurse Specialist, EndofLife Care, Northern Health , BC Della Roberts, RN, MSN, CHPCN(C), Clinical Nurse Specialist, Hospice Palliative Care, Delta and White Rock/South Surrey Health Services, BC Colleen Sherriff, RN, Systemic Therapy, Fraser Valley Cancer Center, BC Ann Syme, RN, MSN, Provincial Leader, Pain and Symptom Management/Palliative Care, BC Cancer Agency Carolyn Tayler, RN, BN, MSA, CON(C), Director Hospice Palliative and End of Life Care, Northern Health , BC Laura Tremblay, BSc(Pharm), Pain & Symptom Management / Palliative Care Team, BC Cancer Agency, Fraser Valley Centre. Production Support and Review Coordination Barbara McLeod, Project Coordinator Carolyn Tayler Colleen Sheriff, Researcher Ann Syme Reviewed and adapted for Northern Health by: Northern Health Hospice Palliative Care Consult Team Nicole Dahlen BScPharm Sandi Armitage RN, BSN, CHPCN(C) Cathy Czeichmeister RN, MSc, CHPCN(C) Judy Lett RN, BScN, MSc, GNC(C) Lynn Shervill RN, CON(C) BA Joan Patriquin RN Elaine Minifie RN Steve Ashwell MD Inban Reddy MD Biz Basian MDCM, GPO Melinda Allison BA, MSW (cand.) Document1 (NHA) (Northeast) (Prince George) (Northern Interior – outside Prince George) (Northwest – Smithers and area) (Northwest – Prince Rupert and area) (Northwest – Kitimat/Terrace and area) (Northeast) (Northern Interior) (Northwest) (NHA) Page 5 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition NH Palliative Symptom Guidelines 1st Edition (December 2004) Developed by: Gillian Fyles MD Andrea Hoye RN, BSN, CHPCN Tammy McCluskey RN, BSN, CHPCN Elizabeth Landecker MD Ian Petterson BScPharm, PharmD (CCSI – Kelowna) (Vernon) (Trail) (Penticton) (Salmon Arm) Under the direction of the Interior Health Hospice Palliative Working Group as a part of Home & Community care Planning & Development Reviewed and adapted for Northern Health by: Dana Cole BScPharm, PharmD Judy Firth RN CareyAnne Lawson BScChem, BScPharm Phillip Staniland MD Document1 (Prince George) (Prince George) (Prince George) (Prince George) Page 6 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition INTRODUCTION Palliative care requires an interdisciplinary, total person approach with a goal to allow one an opportunity to achieve physical, emotional and spiritual comfort. The following definitions help us to understand Northern Health’s vision and commitment to providing high quality services that are competent, compassionate and respectful of all people who are dying and their families.(1) Palliative Care “Palliative care means the specialized care of people who are dying – care aimed at alleviating suffering (physical, emotional, psychosocial or spiritual), rather than curing. The term palliative care is generally used in association with people who have an active, progressive and advanced disease, with little or no prospect of cure.”(1) Hospice Palliative Care Hospice Palliative Care is the nationally accepted term that “aims to relieve suffering and improve the quality of living and dying. Hospice palliative care strives to help patients and families address physical, psychological, social, spiritual and practical issues, and their associated expectations, needs, hopes and fears; prepare for and manage self determined life closure and the dying process; cope with loss and grief during the illness and bereavement. Hospice palliative care aims to treat all active issues; prevent new issues from occurring; and promote opportunities for meaningful and valuable experiences, personal and spiritual growth, and selfactualization; it is appropriate for any patient and/or family living with, or at risk of developing, a life threatening illness due to any diagnosis, with any prognosis, regardless of age, and at any time they have unmet expectations and/or unmet needs, and are prepared to accept care”.(2) EndofLife Care “Endoflife care is the term used for the range of clinical and support services appropriate for dying people and their families. The goal of endoflife care is the same regardless of the setting – to ensure the best possible quality of life for dying people and their families”.(1) Textbook Resources In our Northern Health HPC program we have standardized textbooks to support hospice palliative and endoflife care. The following textbooks have been provided in care facilities for professional caregivers to use in their clinical practice. 1. Victoria Hospice Society. (2006). Medical care of the dying. (4th ed.). Victoria, B.C.: Victoria Hospice Society, Learning Centre for Palliative Care. Document1 Page 7 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 2. Victoria Hospice Society. (2003). Transitions in dying and bereavement: a psychological handbook for hospice and palliative care. Victoria Hospice Society: Health Professions Press. 3. Capital Health. (2006). 99 Common Questions (and more) About Hospice Palliative Care – A nurse’s handbook. 3 rd Edition. Regional Palliative Care Program: Capital Health, Edmonton, Canada. References 1. British Columbia Ministry of Health. A Provincial Framework for EndofLife Care : 2006 2. Ferris FD, Balfour HM, Bowen K, Farley J, Hardwick M, Lamontagne C, et al. A model to guide hospice palliative care 2002.[cited 2006 November]; Available from: http://www.chpca.net/publications/norms/AModeltoGuide HospicePalliativeCare2002.pdf Document1 Page 8 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition What is EvidenceBased Palliative Care?(1) Four important points are: · “Evidencebased practice is the conscious, explicit and judicious use of current evidence in making decisions about the care of individual patients. · It is more difficult to measure quality of life and altered outcomes in patients and families whose illness or frailty make it difficult to collect data. · Outcome and quality of life measures need to be sensitive to the wider aspects of palliative care, not merely mortality, function, or absence of symptoms. · Those working in palliative care must use existing research through appropriate systematic reviews to maximize the value of data yielded in caring for patients and families”. What is a Clinical Practice Guideline (CPG)? Clinical Practice Guidelines are “systematically developed statements to assist practitioner and patient decisions about appropriate health care for specific clinical circumstances”.(2) “Their purpose is to make explicit recommendations with a definite intent to influence what clinicians do.”(3, 4) Why do we need to use EvidenceBased Clinical Practice Guidelines in Hospice Palliative Care? We need to use Clinical Practice Guidelines in Hospice Palliative Care to help us provide the best care possible. Hospice Palliative Care Clinical Practice Guidelines will help us to: · Inform health care providers, patients and families. · Educate health care providers and the public. · Include all members of the health care team. · Improve clinical decisionmaking. · Reduce variation in professional practice. · Ensure equitable allocation of resources. · Measure the quality of our care. · Identify opportunities for improvement. · Improve management of the health care system. · Provide a foundation for the future. What are the Hospice Palliative Care Symptom Guidelines? These guidelines are one of many resources available to health care professionals in Northern Health to improve health care outcomes in hospice palliative/endoflife care. These guidelines provide recommendations based on scientific evidence and expert clinical opinion. They provide practical and easytofollow advice to health care providers for effective patient care. The guidelines are not an all inclusive list of symptom guidelines. Rather, they are intended to be a convenient resource for some of the more common symptoms Document1 Page 9 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition experienced by adult patients ( ≥ 19 years of age) and their families who are living with advanced life threatening illness. As they are symptom guidelines only, they do not replace individual patient and family assessment and/or clinical judgment within the scope of professional practice. As these Hospice Palliative Care Symptom Guidelines are a work in progress and evidence changes, we encourage providers to be aware of this. We welcome and appreciate feedback. What is the purpose of using the AGREE Instrument? The purpose of using the Appraisal of Guidelines & Evaluation (AGREE) Instrument is to provide a framework for assessing the quality of clinical practice guidelines. The AGREE Instrument was used to ensure a structured and rigorous development process and as a selfassessment tool to ensure that the guidelines were sound before adopting the recommendations. It is suggested that the AGREE Instrument is perceived as reflecting the current state of knowledge in the field.(4) The number of appraisers for each of the Northern Health Symptom Guidelines ranged between five and eight. All guidelines received two external reviews by a physician and pharmacist. Each guideline received an overall assessment based on four options: 1. ‘strongly recommend’ 2. ‘recommend (with provisos and alterations)’ 3. ‘would not recommend’ 4. ‘unsure’ A summary of the quality of the Symptom Guidelines is currently under development. References 1. Higginson IJ. Evidencebased palliative care? European Journal of Palliative Care. 1999;6(6):18893. 2. Field MJ, Lohr KN, editors. Guidelines for clinical practice. From development to use. Washington, D. C.: Institute of Medicine, National Academy Press; 1992. 3. Hayward RSA, Wilson MC, Tunis SR, Bass EB, Guyatt G, for the EvidenceBased Medicine Working Group. Users’ guides to the medical literature VIII. How to use clinical practice guidelines. Are the recommendations valid? Journal of the American Medical Association. 1995;274:5704. 4. The Agree Collaboration. Appraisal of guidelines for research and evaluation (AGREE) instrument. September 2001 [cited 2006 November]; Available from: http://www.agreecollaboration.org/ 5. The BC Ministry of Health Guidelines and Protocols Advisory Committee. August 9, 2006 [cited January 18, 2005]; Available from: http://www.health.gov.bc.ca/msp/protoguides/index.ht mL 6. Weschules DJ. Development of guidelines for palliative care. Pharmacotherapy, Journal of Pain and Palliative Care Pharmacotherapy. 2005;19(4):2538. Document1 Page 10 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition SYMPTOM ASSESSMENT ACRONYM The Symptom Assessment Acronym is a tool to aid in a systematic assessment approach to whatever hospice palliative care symptom you are reviewing. Other aids are available however; in Northern Health we found this Symptom Assessment Acronym helpful. We recommend this tool for our Northern Health care providers to guide a consistent and comprehensive symptom assessment in hospice palliative care. Assessment using Acronym O, P, Q, R, S, T, U and V (1,2,3,4,5,6,7,8,9) * O P When did it begin? How long does it last? How often does it occur? Onset Provoking / What brings it on? What makes it better? What makes it worse? Palliating Q R What does it feel like? Can you describe it? Quality Region / Where is it? Does it spread anywhere? Radiation S T U Severity Treatment Understanding/ What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Document1 Page 11 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition References 1. Roberts D, McLeod B. Hospice Palliative Care Symptom Assessment Guide and Guideline for Use of the Form. In: Fraser South Health Region, editor. 1st ed: Fraser South Health Region; 2004. 2. Jarvis C, Thomas P, Strandberg K. The Complete Health History. Physical examination and health assessment 3rd ed. Philadelphia: W. B. Saunders Company; 2000. p. 79102. 3. McCaffery M, Pasero C. Assessment. Pain: Clinical Manual. 2nd ed. St. Louis: Mosby; 1999. p. 35102. 4. Pain General Information. In: Neron A, editor. Care Beyond Cure A Pharmacotherapeutic Guide to Palliative Care: Pharmacy Specialty Group on Palliative Care Canadian Society of Hospital Pharmacists in collaboration with Sabex Inc.; 2000. p. 58. 5. Bates BP, Benjamin R, Northway DI. PQRST: A mnemonic to communicate a change in condition. Journal of the American Medical Directors Association. 2002 January/February;3(10):235. 6. Foley KM. Acute and Chronic cancer pain syndromes. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 298 316. 7. Downing GM. Pain Assessment. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 11958. 8. Part I Physical Symptoms. In: Peden J, deMoissac D, MacMillan K, MushaniKanji T, editors. 99 Common Questions (and more) about hospice palliative care A nurse’s handbook. 3rd ed. Edmonton, Alberta: Regional Palliative Care Program, Capital Health; 2006. p. 296. 9. Muir J. Unrelieved Pain. Nursing bc. 2006 October;38(4):225. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 12 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition AMYOTROPHIC LATERAL SCLEROSIS (ALS) Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Although ALS creates many unique challenges, basic principles of palliative care support comfort and dignity. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced Amyotrophic Lateral Sclerosis (ALS). This guideline does not address disease specific approaches in the management of ALS. While most cases of ALS occur sporadically, approximately 10% of cases are familial and 2% result from a specific gene defect on chromosome 21.(14) ALS has a world wide incidence of approximately 6 to 8 per 100,000; has greater incidence in males than females and usually occurs in mid life.(1, 2, 5, 6) Average survival from diagnosis is about 3 to 5 years,(2, 4, 6, 7) with a range of 6 months to 20+ years(4). Survival time is less with bulbar onset (median 1 year) than limb onset (median 2.5 years).(1) Survival time is generally prolonged in younger patients.(2) Fasciculation’s (muscle twitching) are a prominent feature of ALS(1) in coexistence with muscle atrophy, weakness and cramps.(2, 4, 6) Definition of Terms ALS (also known as Lou Gehrig’s disease) is a progressive fatal type of motor neuron disease resulting in spasticity, diffuse muscular atrophy and weakness.(4, 7) ALS is the most common type of motor neuron disease (MND).(1, 6) ALS was named according to its clinical picture (muscle wasting is amyotrophy) and pathological finding (hardening of the lateral aspects of the spinal cord secondary to gliosis of the pyramidal tracts is lateral sclerosis).(2) Standard of Care 1. Background 2. Assessment of ALS symptoms 3. EndofLife Discussions 4. Symptom Treatment Document1 Page 13 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 1 Background New Treatment Approaches: Research has linked ALS with high levels of glutamate, the primary excitatory neurotransmitter in the central nervous system. There is a theory that glutamate accumulates in nerve cell synapses, eventually destroying the nerve cell. Riluzole, the first drug specifically to treat ALS, inhibits the release of glutamate.(2, 3, 5, 8) It has been shown to extend the survival time of individuals with ALS.(4, 6) Riluzole has been approved for use in the United States and has conditional approval in Canada. It can be obtained from the Vancouver Coastal ALS Centre or from Neurologists at the EMG Lab at Vancouver General Hospital. Recommended dose for riluzole is 50mg b.i.d. (1,5) Background In North American society, which prizes independence and vitality, a diagnosis of ALS can be devastating.(4) Many people are uncomfortable with the profound physical changes of a disease that generally leaves a person mentally intact. The patient is often very distraught over diminishing quality of life, which raises ethical issues regarding aggressiveness of treatment, ventilation, Do Not Resuscitate (DNR) orders and assisted suicide. Few diseases stimulate such a response of total pain. The patient experiences multiple losses such as mobility, speech, the ability to eat and drink, and independence. They may also experience a loss of some relationships and personal fulfillment provided by a job or recreational activities. The frustration and loss of control may lead to anxiety, anger, depression and controlling behavior. Emotional lability and bouts of crying are common. Up to 50% of ALS patients have pseudobulbar effect, pathological uncontrolled bouts of laughing or crying not concordant with their mood.(1, 4, 8, 9) Families, friends and caregivers may be disturbed by the physical changes and/or perceive the patient’s behavior to be unreasonable or demanding.(4) People often visit less frequently thus increasing the loneliness and isolation the patient feels. Communication and safety can become key concerns. Impulsive behavior may contribute to safety issues.(8) There are many devices available to facilitate these important aspects of life. Referrals to occupational therapists in the local health area or through the closest ALS team are very beneficial.(5) Throughout the illness, patients and families will require support from their neighborhood and community, and many health care providers and agencies.(1, 7, 9) Key resources are the Vancouver Coastal ALS Centre, a provincial resource which provides diagnosis, ongoing medical and multidisciplinary team access. The ALS Center is located at GF Strong Rehabilitation Centre. Another key resource is the ALS Society, which provides information, support, and equipment loan (i.e., electric wheelchairs, Document1 Page 14 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition suction machines) to ALS patients. Their website has links to other ALS organizations and information for patients, families and health care providers. Vancouver Coastal ALS Centre 16047376320 ALS Society of BC 16046850737 or 18007083228 or www.alsbc.ca ALS Society of Alberta 14032283857 or 18883091111 or www.alsab.ca ALS Society of Canada www.als.ca “The psychic burden of caregivers sometimes exceeds that of the patient.”(2, 6, 9) Recommendation 2 Assessment of ALS Symptoms Ongoing comprehensive assessment is the foundation of effective symptom management for patients with Amyotrophic Lateral Sclerosis, including interview, physical assessment, medication review, medical and surgical review, psychosocial review, review of physical environment and appropriate diagnostics. Identifying the underlying symptoms for patients with a diagnosis of ALS is essential in determining the interventions required (see Table 1). · · · · ALS often starts focally with muscle weakness or wasting, eventually spreading bilaterally affecting peripheral and cranial nerves and usually sparing bowel, bladder, sensory and cognitive functions. Brain stem involvement (bulbar ALS) produces dysarthria (slurred speech), dysphagia (swallowing problems), sialorrhea (drooling)(4) and aspiration.(1) It occurs in 20 to 30% of ALS cases(8), especially in older women.(2, 6, 9) Eye movement is usually preserved which may be useful in communication.(2, 46) Respiratory insufficiency is one of the most critical issues for the majority of patients with ALS.(7) Table 1: Symptoms Due to ALS:(2, 6) Directly Indirectly Weakness and atrophy Fasciculations and muscle cramps Spasticity Dysarthria Dysphagia Dyspnea Pathological laughter / tearfulness Psychic disturbances Sleep disturbances Constipation Drooling Thick mucous secretions Symptoms of chronic hypoventilation Pain Document1 Page 15 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 3 End of Life Discussions EndofLife Discussions Endoflife discussions are an integral part of care for patients living with ALS and their families. This document does not provide a comprehensive guide for completing Advanced Care Planning for ALS. Advance Care Planning is a process by which people can think about their values regarding future health care choices, hear medical information that is relevant to their health concerns, communicate wishes and values to their loved ones or agents, and document their choices so the decisions are available to health care providers wherever that person receives care. For more information on Advance Care Planning call the palliative nurse consultant in your HSDA. Contact information can be found on NH iportal site: http://iportal.northernhealth.ca > clinical resources > palliative care Six triggers for initiating discussion about endoflife issues:(7, 10) · · · · · · The patient or family asks – or ‘opens the door’ – for endoflife information and/or interventions (elicited or spontaneous, verbal or nonverbal). Psychological and/or social or spiritual distress or suffering. Pain requiring higher doses of analgesic medications. Dysphagia requiring feeding tube. Dyspnea or symptoms of hypoventilation, a forced vital capacity of 50% or less. Loss of function in two body regions (regions include bulbar, arms and legs). Recommendation 4 Symptom Treatment Swallowing and Nutrition · · · · · Dysphagia is caused by disturbed motility of the tongue, pharynx and esophagus.(2, 9) Nutritional consult and swallowing assessment.(1, 4, 5) Patients with bulbar symptoms early in disease may benefit from enteral feeding (PEG tube).(3, 5, 7, 8, 11) Consideration for PEG placement becomes critical with loss of greater than 10% of prediagnostic body weight(1, 2, 5, 6, 8, 9), for symptomatic dysphagia and before forced vital capacity falls below 50% of predicted.(13, 6, 8, 10, 12) Aspiration may occur with overfeeding (high calorie and/or high volume) through a PEG tube.(2, 5, 6, 9) Nutritional and fluid support in the final stages may not be indicated.(4, 5, 8) Patients and families should be informed that decreasing appetite and interest in food is a natural part of chronic disease.(4) Document1 Page 16 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Choking · · · · · · The fear of ‘choking to death’ is on the mind of many patients living with ALS. Yet, a study of 171 patients who died with ALS found that no patient choked to death.(2, 4, 11) This is helpful information to share with patients and families to relieve unwarranted fears of choking.(2, 11) Educate patient and family about techniques to minimize choking, such as changing diet consistency (thickened fluids and decreasing crunchy or chewy foods), positioning and swallowing techniques (Access Nutrition, Speech Language Pathologist or Occupational Therapist consultation).(2, 4, 8, 9) Teach family and caregivers that a calm reassuring presence assists in management of this symptom.(2, 9) Consider having a suction device available.(4, 10) Suctioning has been found to be most effective in patients who have a tracheostomy.(2, 6, 9) Manually assisted coughing techniques and mechanical insufflationexsufflation devices are effective in clearing excess mucous.(1, 4, 6, 8, 12) Consider lorazepam sublingual or subcutaneous injection available for times of distress.(11) Sialorrhea (drooling) · · · · Saliva production can be decreased in ALS patients but it becomes a problem when swallowing mechanisms are affected.(1, 5, 12) It is important to differentiate between sialorrhea and thick mucous production as treatments vary between the two causes.(1, 8, 12) It is more difficult to initiate a swallow with dry mouth, as saliva acts as an important part of the oral prep phase of the swallow. If dry mouth occurs, medications can be given with a puree food item, such as apple sauce or pudding. The following medications can be used to reduce secretions, but be cautious that the drying effect is not beyond normal or comfortable moisture levels. The mouth should never be so dry that swallowing cannot be easily initiated. The intramuscular route should be avoided in ALS patients due to muscle wasting.(4) Anticholinergic affects of drugs producing a drying effect in the mouth: · · · · · · Glycopyrrolate(4, 6, 9) 0.6 to 1 mg t.i.d. PO(1, 12) OR 0.1 to 0.2 mg S.C. t.i.d.(6, 9) Transdermal scopolamine patch(1, 5) q72 hours.(4) Transdermal patch absorption can be inconsistent in patients with excessive perspiration.(1, 8, 12) Buscopan 10 to 20 mg PO or per rectum q4h to q6h. .(4, 6, 9) Amitriptyline(8, 12) 10 to 150 mg PO daily.(4) Atropine(6, 9) 0.4 to 0.6 mg PO OR S.C. b.i.d. or t.i.d. (4) OR 0.25 to 0.75 mg daily.(8) When oral medications fail to control sialorrhea, botulinum toxin A.(8, 12) 7.5 to 20 units injected into the parotid gland (and submandibular gland if the parotid glands alone are not beneficial) is an alternative.(8) Document1 Page 17 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · Thick mucous production associated with sialorrhea can be treated with propranolol or metoprolol.(4) Guaifenesin is also useful.(1, 5) Dyspnea (shortness of breath) · · · · · · · · · · · Provide information that shortness of breath is a symptom that can be managed by medications and other techniques(2, 9, 11) (see Northern Health Hospice Palliative Care Symptom Guideline for Dyspnea). Patient and family should have early education that medications are available when needed for respiratory insufficiency or pain management. Assess to determine if assisted ventilation through BiPap or other noninvasive ventilation device would be beneficial.(1, 2, 511) Noninvasive ventilation devices are often instituted when forced vital capacity is less than 50%.(8) Mechanical ventilation is seldom appropriate in end stage disease. Some clients are well established on BiPap, which is noninvasive. Loss of bulbar muscle tone and difficulty clearing secretions reduce tolerance of noninvasive devices and may define the limit of their use.(12) Position so that respiratory movement is facilitated.(9) Use fresh air moving past the face, relaxation and reassurance to relieve shortness of breath.(4) Pace activities that provoke increased breathlessness.(5) Use oxygen for hypoxia only.(9) Treat reversible causes.(9) Initiate opioids when dyspnea is uncomfortable. For pharmacologic management (see Northern Health Hospice Palliative Care Symptom Guideline for Dyspnea). Pain · · · · · · · · Usually musculoskeletal in origin, secondary to immobility.(1, 46) Severe neck pain, secondary to “floppy head” syndrome (weakness in neck extensors and flexors), can be relieved with the use of a hard Philadelphia or Freeman type collar.(1, 5) Utilize relaxation and diversion to help minimize pain.(10) Regular NSAIDS are useful when pain is mild.(1, 46, 1012) They are particularly useful when active inflammation is present (as in arthritis or tenosynovitis).(1, 5) Acetaminophen 1000 mg PO q6h can be used with NSAIDS or alone.(5, 6) Many patients require regularly scheduled opioids as disease progresses, titrated to point of comfort.(1) Hydroxyzine 50 mg q6h potentiates analgesic effect of the narcotic.(1, 4, 8) It is a direct skeletal muscle relaxant that is not a cortical depressant.(5) For pain with a neuropathic component antidepressants and antiepileptics (gabapentin) are sometimes helpful(1, 4, 12) (see Northern Health Hospice Palliative Care Symptom Guidelines for Pain Management). Document1 Page 18 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Spasticity · · · · Regular stretching is a key to managing spasticity(1, 5, 8) especially for the gastrocnemius muscles (calf muscles).(1) Use gentle physiotherapy, positioning, splints, etc., as appropriate.(1, 46, 8) Range of motion exercise and massage has been shown to decrease spasticity and pain.(4, 7, 8, 10) Use baclofen(6, 9) 5 to 10 mg b.i.d. to t.i.d. up to 20 mg t.i.d.(1) OR 10 to 80 mg daily.(6, 9) Tizanidine (can be added if required) 4 to 8 mg t.i.d. to q.i.d.(1) OR 6 to 24 mg daily.(6, 9) Dysarthria/Communication · · Educate patients and family early about management of speech and communication issues that may arise at the end of life.(4, 6, 8, 10) Refer to an Occupational Therapist or Speech Language Pathologist for communication tools. Depression Reactive depression is common in ALS patients.(1, 9) Up to 75% of ALS patients self report depressive symptoms.(6, 8, 9) · · For treatment of Depression see the Northern Health Hospice Palliative Care Symptom Guidelines for Depression. When selecting an antidepressant consider that amitriptyline is also useful in controlling pseudobulbar effect, drooling and sleep disturbances.(4, 6, 9) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews / systematic reviews, clinical trials, case studies and guidelines / protocols using ALS terms in conjunction with palliative / hospice / end of life / dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Han JJ, Carter GT, Hecht TW, Schuman NE, Weiss MD, Krivickas LS. The Amyotrophic Lateral Sclerosis Center: A Model of Multidisciplinary Management. Critical Reviews in Physical and Rehabilitation Medicine. 2003;15(1):21 40. 2. Borasio GD, Miller RG. Clinical Characteristics and Management of ALS. Seminars in Neurology. 2001;21(2):155 66. 3. Cameron A, Rosenfeld J. Nutritional issues and supplements in amyotrophic lateral sclerosis and other neurodegenerative disorders. Current Opinion in Clinical Nutrition and Metabolic Care. 2002;5:63143. 4. Braithwaite D. Amyotrophic Lateral Sclerosis (ALS). In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 47684. 5. Carter GT, Miller RG. Comprehensive Management of Amyotrophic Lateral Sclerosis. Physical Medicine and Rehabilitation Clinics of North America. 1998 February;9(1):27184. Document1 Page 19 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 6. Borasio GD, Rogers A, Voltz R. Palliative medicine in nonmalignant neurological disorders. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Care. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 92534. 7. Mitsumoto H, The ALS Peer Workgroup Members. Completing the Continuum of ALS Care: A Consensus Document. Missoula, Montana: The Robert Wood Johnson Foundation; 2004 January. 8. Simmons Z. Management Strategies for Patients With Amyotrophic Lateral Sclerosis from Diagnosis Through Death. The Neurologist. 2005 September;11(5):25770. 9. Borasio GD, Voltz R, Miller RG. Palliative Care in Amyotrophic Lateral Sclerosis. Neuologic Clinics. 2001 November;19(4):82947. 10. Mitsumoto H, al E. Promoting excellence in endoflife care in ALS. Amyotrophic Lateral Sclerosis. 2005;6:14554. 11. Neudert C, Oliver D, Wasner M, Borasio GD. The course of the terminal phase in patients with amyotrophic lateral sclerosis. Journal of Neurology. 2001;248:6126. 12. Millar RG, al E, The ALS Practice Parameters Task Force. Practice Parameter: The Care of the Patient with Amyotrophic Lateral Sclerosis (an EvidencedBased Review) Report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 1999;52:131123. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 20 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition ASCITES Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of ascites. This guideline does not address disease specific approaches in the management of ascites. Ascites may develop in 15% to 50% of patients with malignancies(1, 2) but most cases (80%) of ascites will be related to cirrhosis.(3) Definition of Terms Ascites is the accumulation of fluid within the peritoneal cavity.(2) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Assessment of Ascites Ongoing comprehensive assessment is the foundation of effective management of ascites, including interview, physical assessment, medication review, medical and surgical review, psychosocial review, review of physical environment and appropriate diagnostics. Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family (see Table 1). Document1 Page 21 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1: Ascites Assessment using Acronym O, P, Q , R, S, T , U and V * O P When did it begin? How often does it occur? Onset Provoking / What brought it on? What makes it better? What makes it worse? Palliating Q R What does it feel like? Can you describe it? Have you noticed weight gain? Quality Region / Where is the pressure? Is it spreading? Radiation S T U Severity Treatment What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom – nausea, loss of appetite, pain? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? Understanding/ How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Diagnostic Tests: · · · Using abdominal radiography, ascites may demonstrate a ‘ground glass appearance’.(1) Ultrasound or CT scan may be required to demonstrate small volumes of free peritoneal fluid.(1) Diagnostic paracentesis may be required to elucidate the type of ascites and should be done on newly diagnosed cases of ascites.(1) Document1 Page 22 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Clinical Signs and Symptoms: · · · · · · · · Abdominal pressure, pain.(1, 3, 4) Anorexia, early satiety, nausea, vomiting.(14) Dyspnea and/or orthopnea.(13) Increased abdominal girth.(2) Peripheral edema.(1, 2) Reduced mobility.(4) Reflux esophagitis.(13) Shifting dullness to percussion and a fluid thrill.(2,5) Recommendation 2 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. The most significant intervention in the management of ascites is identifying underlying cause(s) and treating as appropriate (See Causes of Ascites). While underlying cause(s) may be evident, treatment may not be indicated, depending on the stage of the disease. Identifying the underlying etiology of ascites is essential in determining the interventions required. Causes of ascites:(1, 3) · · · · Cirrhosis – is the predominant cause in 80% of cases. It presents as transudative ascites (ascitic fluid protein concentration of less than 2.5g/dl). Malignancy – causes 10% of cases. They are mostly (80%) epithelial related ovarian, uterus, breast, colon, gastric and pancreatic however the remaining 20% have tumours of primary unknown origin. The fluid produced in malignancy is exudative (ascitic fluid protein concentration of greater than 2.5g/dl). Heart failure – is responsible for 3% of cases. The fluid produced is transudative. Renal related – 3%, tuberculosis – 2%, pancreatitis – 2% and miscellaneous – 1% or absent.(5, 9) Types of ascites:(6) · · · · Raised hydrostatic pressure – caused by cirrhosis, congestive heart failure, inferior vena cava obstruction and hepatic vein occlusion. Decreased osmotic pressure – caused by protein depletion (nephrotic syndrome, proteinlosing enteropathy), reduced protein intake (malnutrition) or reduced protein production (cirrhosis). Fluid production exceeding resorptive capacity – caused by infection or neoplasms. Chylous – due to obstruction and leakage of the lymphatics draining the gut. Document1 Page 23 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 3 Education Education of patient and their family should comprise discussion of treatment methods of ascites and the value of paracentesis when the patient becomes symptomatic.(3) Recommendation 4 · · · · · · Treatment: Nonpharmacological Observation is appropriate when the condition is asymptomatic.(3) Observation would include measuring the abdominal girth at a marked site each week(6) as well as appropriately scheduled weight measurement. Paracentesis is the draining of ascitic fluid via a catheter inserted through the abdominal wall. This may be achieved under ultrasound guidance or in an outpatient setting for quick relief of symptoms. Generally, upwards of 5 litres of fluid may be removed with little risk of hypotension or hypovolemic shock when patient screening is applied.(6) Intravenous hydration should be considered if the patient is hypotensive, dehydrated or known to have severe renal impairment and paracentesis is still indicated.(4) If there is leakage over the paracentesis site an ostomy bag can be applied.(2, 6) Single or repeated paracentesis in patients with advanced cancer does not significantly lower serum protein.(2) Peritoneal catheters (smaller bore catheter) may be useful when ascites is rapidly accumulating and requiring frequent paracentesis for symptom control. This significantly exposes the patient to the risk of peritonitis and is usually reserved for patients in the terminal phase of their illness, with a prognosis of weeks.(3, 5, 7, 8) Radiation therapy and chemotherapy may be useful in cases where a meaningful response to tumour growth may be expected, such as lymphoma.(1) Salt restriction plays an important role where fluid is transudative, but may also provide relief in patients with cancer and hepatic metastases.(1, 3) A low fat diet and increase in mediumchain triglyceride intake may be useful in patients with chylous ascites.(1) Recommendation 5 Pharmacological Diuretics: · · · · Diuretics should be considered in all patients, but has to be evaluated individually. Patients with malignant ascites due to massive hepatic metastases seem to respond better to diuretics than those with malignant ascites due to peritoneal carcinomatosis or chylous ascites.(4) Diuretics may help with portal hypertension (hepatic metastases, heart failure and cirrhosis)(3) and should be tried in most patients after their first abdominal paracentesis as approximately onethird of patients are shown to benefit.(9) Goal of diuretic therapy would be to achieve a weight loss of 0.5 to 1 kg per day.(6) Spironolactone 100 mg daily(2) titrated slowly to 400 mg daily – titrated to remove enough fluid for comfort.(1, 3, 6) Document1 Page 24 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · Furosemide 40 to 120 mg daily may be added to spironolactone to improve the effect (2, 3, 6) and prevent hyperkalemia. Furosemide given by continuous infusion is reported to produce significant diuresis and marked relief of ascites.(2) When utilizing diuretics monitor electrolytes, renal function, drug interactions and blood pressure weekly.(6) Octreotide: · Octreotide in doses of 200 to 600 mcg S.C. per day has shown promise in cases of ascites refractory to paracentesis.(2, 10) Dosing frequency should be in two to three divided doses per day. References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines / protocols using ascites terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Kichian K, Bain VG. Jaundice, ascites and hepatic encephalopathy. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine 3rd ed. New York, New York Oxford University Press Inc., New York; 2005. p. 50720. 2. Waller A, Caroline NL. Ascites. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA: Butterworth Heinemann; 2000. p. 2316. 3. Carter B, Black F, Downing GM. Bowel Care Constipation and Diarrhea. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 34162. 4. Becker G, Galandi D, Blum HE. Malignant ascites: Systematic review and guideline for treatment. European Journal of Cancer. 2005 November 8, 2005;42:58997. 5. Brooks RA, Herzog TJ. Longterm semipermanent catheter use for the palliation of malignant ascites. Gynecologic Oncology. 2006;101:3602. 6. Dean M, Harris JD, Regnard C, Hockley J. Ascites. Symptom Relief in Palliative Care. Oxford, United Kingdom: RadcliffePublishing Ltd.; 2006. p. 636. 7. Iyengar TD, Herzog TJ. Management of symptomatic ascites in recurrent ovarian patients using an intraabdominal semipermanent catheter. American Journal of Hospice and Palliative Care. January/February 2002;19(1):358. 8. Sartori S, et al. Sonographically Guided Peritoneal Catheter Placement in the Palliation of Malignant Ascites in EndStage Malignancies. American Journal of Roentgenology. May 30, 2002;179:161820. 9. Gough IR, Balderson GA. Malignant Ascites. Cancer. 1993;71:237782. 10. Cairns W, Malone R. Octreotide as an agent for the relief of malignant ascites in palliative care patients. Palliative Medicine. 1999;13:42930. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 25 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition BOWEL CARE Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of constipation. This guideline does not address disease specific approaches in the management of constipation. Bowel pattern changes cause distress in up to 18% of palliative care patients and rises to 80% or higher at the end of life.(1,2) Constipation is most frequent among patients treated with opioids – 40 to 50%.(3, 4) It significantly impacts quality of life and may be a cause of restlessness.(5) Constipation is more common in women and the elderly.(6) Diarrhea is less common occurring in less than 10% of cancer patients.(7, 8) Definition of Terms Constipation can be defined as “unduly infrequent and difficult evacuation of the bowels” that is “reduced frequency of bowel movements than is normal for the individual concerned, which may lead to pain and discomfort”.(9) Ingestion induced constipation results from inadequate intake of fluids and/or fiber or intake of constipating foods (cheese or milk) or by drugs.(1, 4) Other forms of constipation are: · hypotonic – caused by a decreased rate of water absorption and muscular tone · dyschezia (or habit) caused by ignoring the urge to defecate · chronic hypertonic – caused by excess colonic muscular activity secondary to hypersegmentation and prominent creasing of feces (rather than propulsion) and fecal impaction (obstruction).(1) Diarrhea is defined as 3 or more loose, watery stools per day. (1, 8) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Document1 Page 26 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 1 Assessment of Constipation / Diarrhea Ongoing comprehensive assessment is the foundation of effective management of constipation, including interview, physical assessment (abdomen/bowel sounds/skin), medication review, medical and surgical review (xray of the abdomen may be indicated where obstruction is suspected), psychosocial review, review of physical environment and appropriate diagnostics (see Table 1). Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family.(2, 7, 911) Complete a bowel assessment and consistently reevaluate.(1, 12) An excellent resource for guidance on interview questions for Constipation(13) and Diarrhea(14) can be found on the BC Cancer Agency website (www.bccancer.bc.ca > Health Professionals Info > Nursing > References > TelConsultProtocols). Table 1: Constipation/Diarrhea Assessment using Acronym O, P, Q , R, S, T , U and V * O P Onset Provoking / When did it begin? How long does it last? How often does it occur? History of bowel habits and patterns, usual time of defecations? Date of last bowel movement? What brings it on? What makes it better? What makes it worse? What has your diet been like – solids and fluids? What makes the stools softer/harder/watery, more/less frequent? Palliating Q R Quality Region / What does it feel like? Can you describe it? What have the stools looked like? Do you have to strain? Flatulence? Does the feeling spread anywhere? Do you have any hemorrhoids, bleeding, pain? Radiation S T U Severity Treatment What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right Now? At Best? At Worst? On Average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? For example, pain, nausea/vomiting, bloating, loss of appetite? What medications and treatments are you currently using? If you are using laxatives, how effective are they? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What is your daily fluid and fibre intake? What do you believe is causing this symptom? Understanding/ How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? *also include a Physical Assessment (as appropriate for symptom) Document1 Page 27 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 2 Diagnosis Identifying the underlying etiology of constipation and diarrhea is essential in determining the interventions required (see Tables 2 and 3).(6, 10, 11) Table 2: Causes of Constipation in Advanced Cancer Patients(1, 6, 7, 13) Structural abnormalities GI Obstruction Pelvic tumour mass Radiation fibrosis Painful anorectal conditions (anal fissure, hemorrhoids, perianal abscess) Drugs Opioids Drugs with anticholinergic action anticholinergics, antispasmodics, antidepressants, phenothiazines, haloperidol, antacids Antiemetics – 5HT 3 antagonists Diuretics Anticonvulsants Iron Antihypertensives Chemotherapy agents –vinca alkaloids Metabolic disturbances Dehydration Hyperglycemia Hypokalemia or Hypercalcemia Uremia Hypothyroidism Neurological disorders Cerebral tumours Spinal cord involvement/compression Sacral nerve infiltration Autonomic failure General Advanced age Inactivity Depression Sedation Decreased intake Low fiber diet Poor fluid intake Physical or social impediments Constipation can be multifactorial in nature.(10, 15, 16) Document1 Page 28 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 3: Causes of Diarrhea in Advanced Disease(1, 6, 7, 14) Obstruction Malignant tumour Fecal impaction Opioid bowel syndrome Drugs Laxatives Antacids Antibiotics Chemotherapy agents – 5flourouracil, mitomycin NSAIDs – diclofenac, indomethacin Iron preparations Disaccharide containing elixirs Malabsorption Pancreatic carcinoma or insufficiency Gastrectomy Ileal resection Colectomy Tumour Cancer of the colon or rectum Pancreatic islet cell tumour Carcinoid tumour Radiation Abdominal or pelvic radiation with or without chemotherapy (RT induced enteritis) Concurrent disease Diabetes mellitus Hyperthyroidism Inflammatory bowel syndrome – Crohn’s Irritable bowel syndrome – Colitis Gastrointestinal infection – C. Difficile Diet Bran Fruit Hot spices Alcohol Recommendation 3 Education · · · · · Even in the absence of oral intake, the body continues to produce 1 to 2 ounces of stool per day.(17) It is not necessary to have a bowel movement every day. As long as stools are soft and easy to pass, every 2 to 3 days is acceptable.(12) “Normal” bowel movements vary from person to person.(13) If appetite is small, try to incorporate nutritious liquids such as milkshakes, cream soups, fruit juice.(13) Encourage use of a bowel record to evaluate the effectiveness of treatment strategies. (27) Document1 Page 29 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · The desired outcomes of a treatment strategy is a comfortable bowel movement at least every several days with the minimum required use of laxatives as well as satisfaction of the patient and family. (27) Recommendation 4 Treatment Nonpharmacological Constipation: · · · Incorporate constipation prevention strategies for as long as possible and appropriate, including: – Encourage fluid intake of at least 56 eight ounce cups per day (unless medically contraindicated.) (27) Caffeinated and alcoholic beverages are not included in total daily fluid intake because of their diuretic effect. (27) – Encourage daily intake of natural dietary fibre (1225 grams per day) (27) by increasing fruit (prunes), other natural agents, and/or dietary fiber (only for those with adequate fluid and mobility). (1, 3, 7, 11, 15, 18, 19) A fruit laxative can be made with prunes, dates, figs and raisins.(10, 12) Fibre usually becomes effective after two to three days. (27) Attempts at defecating should be made 30 to 60 minutes following ingestion of a meal to take advantage of the gastro colic reflex.(1, 10, 11) Bowel action should be initiated when it is “normal and convenient” for the patient in a sitting position. It should be made easy to achieve quick access to a toilet when having the urge to defecate.(27) This can be facilitated by using; raised toilet seats, commodes and ensure adequate pain control for movement and comfort.(1, 10) · · · Provide privacy during toileting.(1, 3, 10, 11, 15, 19, 20) Avoid excessive straining (this can complicate some medical conditions).(1, 10) If possible, assist to allow leaning slightly forward on the toilet/commode with feet supported to reduce the need for straining. (27) Encourage and assist with physical activity suited to the patient’s abilities.(13,27) Diarrhea: · · · · For most patients with diarrhea decreasing insoluble fiber intake is helpful, however if there is excessive liquid in the bowel an absorbent can be helpful (crackers). If over stimulation of the bowel is suspected reducing intake to sips of fluid for 24 to 48 hours can be helpful.(1, 8) Limit consumption of insoluble fiber, large meals, fatty foods, caffeine (14) and dairy products.(6) Maintain hydration and electrolytes as appropriate (particularly in cases of severe diarrhea).(1, 14) Ringers lactate is the preferred solution for parenteral hydration.(21) Rehydration can also be done orally, if the dehydration is not severe, with the WHO rehydration fluid (2 gm salt plus 50 gm sugar to 1 litre of water).(8, 21) A single liquid or loose stool usually does not require intervention.(1) Document1 Page 30 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · Good hygiene and application of hydrocolloid dressings(21) or barrier cream will help prevent excoriation with diarrhea.(1, 8) If already inflamed or excoriated use a corticosteroid cream for 1 to 2 days.(8) Persisting diarrhea can have severe effects on image, mood and relationships, which will need support.(21) Recommendation 5 Treatment: Pharmacological Constipation: · · · · · · · · · · · · · · · · · · · Constipation is a common side effect of all opioids.(1, 12) Patients often stop opioid therapy because of opioid induced constipation.(22) Opioid induced constipation is much easier to prevent than treat.(23) Opioids cause decreased motility (by suppression of intestinal peristalsis) and increased water and electrolyte reabsorption in the small intestine and colon.(1,4) Transdermal fentanyl(4) and methadone(16, 20) have been shown to produce less constipation. Consider opioid rotation for severe refractory constipation.(16, 20) Tolerance will not develop to the constipating effects of opioids.(15, 23) The constipating effect of opioids are not dose dependant.(24) Laxatives are available under the Palliative Benefit Program but require a prescription. Consider patient preferences when determining bowel regime.(18) In randomized clinical trial comparing senna to lactulose – senna was preferred secondary to a favorable toxicity profile and cost advantage.(25) The sweet taste of lactulose can cause problems with compliance.(7) Sorbitol has been found to be less nauseating.(6) Start laxatives on a regular basis for all patients taking opioids(1, 12, 17, 19, 24) (see Appendix A). Based on the bowel pattern, time since last bowel movement and bowel medication previously being used, determine the level of the bowel protocol for medications.(12) Use a step wise approach, titrate the laxatives(1, 12, 16, 24) according to the bowel protocol to ensure regular bowel movements. Aim for soft formed stool at least once every 2 to 3 days.(12) Three days without a bowel movement requires intervention.(1, 12) The continued use of docusate in the palliative care setting is based on inadequate experimental evidence.(22, 26) Rectal laxative should never accompany an inadequate prescription of oral laxative.(7) Avoid use of rectal enemas and suppositories while receiving chemotherapy. Avoid use of bulk forming agents (fiber) in patients with poor oral fluid intake. The patient must be able to tolerate 1.5 to 2 litres of fluid per day.(1, 3, 11) This makes bulk forming agents a poor choice in cancer patients.(7) They may worsen with an incipient obstruction.(7) Osmotic laxatives should be accompanied by an increase in fluid intake.(7) Document1 Page 31 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · Metoclopramide inhibits dopamine centrally and peripherally, therefore increasing peristalsis in the digestive tract and decreasing nausea and vomiting.(3) o Metoclopramide 10 to 20 mg PO q6h.(10) There is some evidence to support the use of polyethylene glycol as a laxative for opioid induced constipation.(22) Polyethylene glycol 10 to 30 g PO daily to b.i.d. or 60 to 240 g for evacuation.(1) Oral Laxatives: Type : Action : Sodium docusate Predominantly softening – surfactant Detergent, increase water penetration Lactulose Predominantly softening – osmotic laxative Retain water in small gut Sorbitol Predominantly softening – osmotic cathartic Retain water in small gut Methyl cellulose Predominantly softening – bulk forming agent Normalize stool volume Magnesium sulphate Predominantly softening – saline laxative Retain water and strong purgative action Polyethylene glycol Predominantly softening – osmotic cathartic Increases fluid and purgative action Sennosides Peristalsis stimulating – anthracenes Bisacodyl Peristalsis stimulating – polyphenolic Reduces water and electrolyte absorption and purgative action Reduces water and electrolyte absorption and purgative action Rectal Laxatives: Type : Action : Bisacodyl suppository Peristalsis stimulating – polyphenolic Glycerin suppository Predominantly softening – osmotic laxative Evacuates stools from rectum or stoma: for colonic inertia Softens stools in rectum or stoma Phosphate Enema Peristalsis stimulating – saline laxative Evacuates stool from lower bowel Oil enema Predominantly softening – lubricant laxative Softens hard impacted stool · · · · Latency of action of docusate sodium is one to three days.(7) Latency of action of lactulose and sorbitol is one to two(6) and up to three days.(7) Latency of action of peristalsis stimulating laxatives is 6 to 12 hours.(7) Enemas may need to be repeated to clear the bowel of hard impacted stool.(7) Document1 Page 32 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · Latency of action of suppositories and enemas is 15 to 60 minutes.(6) Diarrhea: Diarrhea can be caused by over use of laxatives or can be a side effect of radiation, chemotherapy or surgical treatments.(1, 8, 21) Symptomatic relief is generally achieved with nonspecific antidiarrheal agents – loperamide PO up to 16 mg daily(8) or codeine 10 to 60 mg PO q4h.(7) Unlike constipation, where multiple drugs are used simultaneously, a single drug should be used for diarrhea and care should be taken to avoid subtherapeutic doses.(7) Metronidazole is recommended for C. Difficile diarrhea(6) metronidazole 500 mg PO t.i.d.(8) Oral vancomycin is an alternative to metronidazole. Octreotide is an effective therapy for severe refractory diarrhea.(21) Octreotide 300 to 600 mcg per day S.C.(21) in 23 divided doses. References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using constipation/diarrhea terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Carter B, Black F, Downing GM. Bowel Care Constipation and Diarrhea. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 34162. 2. McMillan SC. Presence and severity of constipation in hospice patients with advanced cancer. American Journal of Hospice and Palliative Care. November/December 2002;19(6):42630. 3. Tamayo AC, DiazZuluaga PA. Management of opioidinduced bowel dysfunction in cancer patients. Support Care Cancer. 2004 June 19;12:6138. 4. Choi YS, Billings A. Opioid Antagonists: A Review of Their Role in Palliative Care, Focusing on Use in Opioid Related Constipation. Journal of Pain and Symptom Management. July 2002;24(1):7190. 5. Goodman ML, Low J, Wilkinson S. Constipation Management in Palliative Care: A Survey of Practices in the United Kingdom. Journal of Pain & Symptom Management. March 2005;29(3):23844. 6. Sykes NP. An investigation of the ability of oral naloxone to correct opioidrelated constipation in patients with an advanced cancer. Palliative Medicine. 1996;10:13544. 7. Fallon M, O’Neill B. ABC of palliative care: Constipation and diarrhoea. British Medical Journal. 1997 November 15;315:12936. 8. Waller A, Caroline NL. Diarrhea. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA; 2000. p. 2239. 9. Goodman ML, Wilkinson S. Laxatives for the management of constipation in palliative care patients. The Cochrane Database of Systematic Reviews. 2006;1. 10. Paolini CA. Symptoms Management at the End of Life. The Journal of the American Osteopathic Association. October 2001;101(10):609 15. 11. Beckwith C. Evidence Based Symptom Control in Palliative Care: Constipation in Palliative Care Patients. Evidence Based Symptom Control in Palliative Care: Systematic Reviews and Validated Clinical Practice Guidelines for 15 Common Problems in Patients with Life Limiting Disease. 2000;8(1):4757. 12. British Columbia Cancer Agency. Suggestions for dealing with constipation – draft Management of Constipation draft. British Columbia Cancer Agency; 2006. 13. BC Cancer Agency Professional Practice Nursing. Telephone Consultation Protocol: Constipation. [cited 2006 August2006];Protocol].Availablefrom: http://www.bccancer.bc.ca/HPI/Nursing/References/TelConsultProtocols/Constipation.htm Document1 Page 33 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 14. BC Cancer Agency Professional Practice Nursing. Telephone Consultation Protocol: Diarrhea. [cited 2006 August 2006];Protocol].Available from: http://www.bccancer.bc.ca/HPI/Nursing/References/TelConsultProtocols/Diarrhea.htm 15. Esper P, Heidrich D. Symptom Clusters in Advanced Illness. Seminars in Oncology Nursing. February 2005;21(1):20 8. 16. Mancini IL, Hanson J, Neumann CM, Bruera E. Opioid Type and Other Clinical Predictors of Laxative Dose in Advanced Cancer Patients: A Retrospective Study. Journal of Palliative Medicine. 2000;3(1):4956. 17. Capital Health Regional Palliative Care Program. Bowel Care Protocol for Palliative Care Patients. March 20,2003[cited2006April2006];Protocol].Availablefrom: http://www.palliative.org/pc/clinicalinfo/Clinical%20Practice%20Guidelines/PDF%20files/Bowel%20Care%20in%20Pa lliative%20Care.pdf 18. Cadd A, et al. Assessment and documentation of bowel care management in palliative care: incorporating patient preferences into the care regimen. Journal of Clinical Nursing. 2000;9:22835. 19. Waller A, Caroline NL. Constipation. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA: Butterworth Heinemann; 2000. p. 197206. 20. Dean M, Harris JD, Regnard C, Hockley J. Constipation. Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 759. 21. Dean M, Harris JD, Regnard C, Hockley J. Diarrhea. Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 814. 22. Wirz S, Klaschik E. Management of constipation in palliative care patients undergoing opioid therapy: Is polyethylene glycol an option? American Journal of Hospice and Palliative Medicine. October 2005;22(5):37581. 23. Ross DD, Alexander CS. Management of Common Symptoms in Terminally Ill Patients: Part II Constipation, Delirium and Dyspnea. American Family Physician. September 15, 2001;64(6):1019 26. 24. Daeninck P, Crawford G. Constipation. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine – A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. p. 20111. 25. Agra Y, Sacristan A, Gonzalez M, Ferrari M, Portugues A, Calvo MJ. Efficacy of senna versus lactulose in terminal cancer patients treated with opioids. Journal of Pain & Symptom Management. 1998 Jan;15(1):17. 26. Hurdon V, Viola R, Schroder C. How Useful is Dousate in Patients at Risk for Constipation? A Systematic Review of the Evidence in the Chronically Ill. Journal of Pain & Symptom Management. February 2000;19(2):1306. 27. Harrigan Consulting. Best Practices for the Nursing Care of the Older Adult. Network of Excellence for Geriatric Services. Northern Health – Clinical Practice Guidelines – Constipation – March 2006. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 34 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix A Example of a Hospice Palliative Care Bowel Protocol 1. Complete Bowel Assessment. 2. Determine Level at which to start, based on bowel pattern, time since last bowel movement and bowel medication use prior to admission. Record Level chosen on Bowel Assessment form. 3. Document all bowel medications administered and bowel movement information on Medical Administration Record (MAR) and nursing notes. Include frequency, character, and amount of bowel movements and laxative interventions. 4. Subsequent rectal and/or abdominal examinations are to be documented on the MAR and nursing notes. INDICATIONS • To prevent opioidinduced constipation. • To manage constipation where dietary measures have failed, or previous laxative treatment unsatisfactory. LEVEL 1 – PREVENTION ONCE DAILY (HS) LEVEL 2 – PREVENTION TWICE DAILY (BID) LEVEL 3 – CONSTIPATION MANAGEMENT No BM for 3 days or more. Do rectal examination and document on Bowel MAR. LEVEL 4 – CONSTIPATION MANAGEMENT (Day 2) No BM or insufficient result. CONTRAINDICATIONS Do not follow protocol for: • Ileostomy. • Complete bowel obstruction. • Diarrhea. • Impaction if present, clear impaction prior to initiating protocol. • Short Bowel Syndrome. • If in doubt, contact MD. Meds: 1. Sennosides 12 mg tablets; 12 to 36 mg (1 to 3 tablets) PO HS Meds: 1. Sennosides 12 mg tablets; 24 to 36 mg (2 to 3 tablets) PO BID 2. Lactulose 15 mL PO BID Continue previous medications PLUS: a), b) or c) Meds: a) If soft stool in rectum Bisacodyl 10 mg supp PR. If not effective within 1 hour, give Microlax or Fleet enema PR. b) If hard or impacted stool in rectum Oil Retention Enema PR. If not effective within 1 hour, give Microlax or Fleet enema PR. Disimpact if indicated (see Hospice Bowel MAR). c) If no stool in rectum Perform abdominal examination and document on Bowel ReAssessment form. Assess abdomen for bowel sounds. If normal, give Microlax or Fleet enema PR +/ Oral Fleet Phospho Soda 15 mL PO. If abnormal, CALL MD/Hospice Palliative Care Team. Nursing Assessment. May repeat above or consult with MD / Hospice Palliative Care Team. OUTCOME: After a BM, resume Level I or II (increasing dose(s) PRN) to maintain a BM at least q 3 days. It is not uncommon to require increasing doses of sennosides as dose of opioid increases. Document1 Page 35 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition COUGH Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Of patients living with and dying from advanced life threatening illness up to 86% experience the symptom of cough.(1, 2) Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of cough. This guideline does not address disease specific approaches in the management of cough. When cough becomes chronic it can be the source of sleep disturbance, agitation or anxiety and becomes exhausting. Cough is both an objective and subjective experience and has been reported that cough is multifactorial in origin in 42% to 62% of cases. It is experienced by 23 to 86% of cancer patients and up to 59% of nonmalignant patients.(1 10) Definition of Terms Cough has two functions: to prevent foreign material entering the lower respiratory tract and to clear secretions from the lungs and bronchial tree.(3) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Assessment of Cough Ongoing comprehensive assessment is the foundation of effective cough management, including interview, physical assessment, medication review, medical and surgical review, psychosocial and physical environment review (including past and present occupation) and appropriate diagnostics (see Table 1). Cough assessment must determine the cause, effectiveness and impact on quality of life.(13, 68, 1012) Document1 Page 36 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1: Cough Assessment using Acronym O, P, Q, R, S, T, U and V (8, 12) * O P When did it begin? How long does it last? How often does it occur? Onset Provoking / What brings it on? What makes it better? What makes it worse? Palliating Q R What does it feel like? Can you describe it? Is it positional? Quality Region / What areas are involved in your cough? Throat? Chest? Radiation S T U Severity Treatment What is the intensity of this symptom (On a scale of 0 to 10, with 0 being none and 10 being worst possible)? Right Now? At Best? At Worst? On Average? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? Understanding/ How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Recommendation 2 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. The most significant intervention in the management of cough is identifying underlying cause(s) and treating as appropriate. While underlying cause(s) may be evident, treatment may not be indicated, depending on the stage of the disease. Whether or not the underlying cause(s) can be relieved or treated, all patients will benefit from management of the symptom using education or medications. Document1 Page 37 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Identifying the underlying etiology of the cough is essential in determining the treatment required (see Table 2).(13, 79, 1113) Table 2: Underlying Causes of Cough & Treatment of Choice Underlying Cause Treatment of Choice Amyotrophic Lateral Sclerosis (ALS) Scopolamine, atropine or glycopyrrolate to reduce secretions to normal and comfortable moisture levels Bronchospasm/Bronchiectasis Bronchodilators, antibiotics Chronic Obstructive Pulmonary Disease (COPD) / Asthma Conventional inhalers, nebulized drugs or saline, steroids to suppress inflammation Congestive Heart Failure Conventional medications to decrease excess fluid ie.) diuretics Suppress and settle with suppressant, anxiolytic, scopolamine or atropine End stage weakness Gastroesophageal reflux H2 inhibitors, proton pump inhibitor, motility agents, elevate head of bed, drain contributing ascites Infection Pneumonia Prevention of aspiration. Oral antibiotics may help decrease productive cough that is disturbing sleep, or causing pain or hemoptysis Malignant pleural effusion Thoracentesis or pleurodesis; lying on the same side can decrease related cough Medications Stop offending ACE inhibitor Post radiation lung damage Steroids Superior Vena Cava (SVC) Obstruction Radiotherapy, steroids Tumour related airway irritation Radiotherapy/brachytherapy, laser treatment, self expandable stents or steroids Upper airway cough syndrome (Postnasal drip) – allergies, infection, sinusitis Nasal steroids or ipratropium. Oral antibiotics for sinusitis, expectorants (guaifenesin) or anti histamine Recommendation 3 Education Cough can be distressing to experience and often more difficult to witness. Providing education regarding the etiology of cough and expectations of treatment is foundational to enhance the patient and family’s ability to cope.(1) Document1 Page 38 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · As a person weakens, the ability to raise sputum is reduced.(1) Teach the patient ‘huffing or forced expiratory technique’ to clear secretions with minimal effort. (8, 12, 14, 15) Recommendation 4 · · · · · · Treatment: Nonpharmacological Positioning to promote and facilitate secretion drainage (postural drainage),(14, 6, 8, 10, 12) but should not be used during acute exacerbation of chronic bronchitis.(8) Avoidance of smoking, chemical irritants or noxious fumes.(4, 810, 12) Nebulized saline, steam or cold air humidifier.(1, 3, 1012) Adequate hydration.(2) Suction is not indicated except in the following situations: When acute fulminant pulmonary edema is present, or to clear bronchial secretions in patients with tracheostomy, or to clear saliva when full esophageal obstruction is present or when bleeding is present in mouth or throat.(1, 10) Provide instruction in anxiety reduction strategies.(8) Recommendation 5 Treatment: Pharmacological For minor or simple cough · expectorants are effective.(1) Guaifenesin is a useful expectorant. For mild to moderate cough · Dextromethorphan (nonopioid) 15 to 30 mg PO q.i.d.(2, 3, 5, 10, 12) For advanced disease multifactorial cough · · · Antitussive opioids include: · Methadone 2.5 to 10 mg PO.(16) Methadone is a powerful antitussive and has activity superior to those of morphine and codeine.(16) Taking it 2 hours before bed is recommended for troublesome night cough.(16) · Hydromorphone 1 to 2 mg PO Q4H.(2, 3, 58, 10, 17) · Hydrocodone 5 to 10 mg PO every 4 to 6 hours with a daily dose no higher than 60 mg.(16) It has greater antitussive activity than codeine but less than morphine.(16) · Morphine up to 5 mg PO every 4 hours.(16) · Codeine 10 to 20 mg PO every 4 to 6 hours, with a daily dose no higher than 120 mg.(16) · Oxycodone 5 mg every 4 hours or 10 mg PO sustainedrelease oxycodone every 12 hours.(16) Dexamethasone 4 to 8 mg PO or I.V. or S.C. daily depending on severity and cause; taper and avoid long term use if possible (increased risk of proximal myopathy which can be very debilitating).(4) For intractable cough nebulized local anesthetics can be useful: (15, 7, 12) · May precipitate bronchospasm in asthmatic patients.(13) Document1 Page 39 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Gag reflex is inhibited after administration, keep NPO for 1 to 2 hours afterward,(13) and rinse and spit after nebulization to minimize numbness of lips and tongue. Use a mouthpiece rather than a mask for inhalation. · Bupivacaine 0.25% 5 mL q4h.(13) · Lidocaine 2% 2 to 5 mL in 1 mL of normal saline q4h.(13) Sodium cromoglycate has been found to be a useful cough suppressant in advanced lung cancer.(8, 18) · · References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using respiratory/cough terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Gallagher R. Cough in Terminal Care. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 363 5. 2. Chan KS, Sham M, M. K., Tse DMW, Thorsen AB. Palliative medicine in malignant respiratory diseases. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 587 618. 3. Leach R. Palliative medicine and nonmalignant, endstage respiratory disease. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 895 916. 4. Esper P, Heidrich D. Symptom Clusters in Advanced Illness. Seminars in Oncology Nursing. February 2005;21(1):20 8. 5. Kvale PA, Simoff M, Prakash UBS. Palliative care. Chest 2003 Jan; 123(1): Suppl: 284S311S. January 2003. 6. Louie K, Bertolino M, Fainsinger R. Management of Intractable Cough. Journal of Palliative Care. 1992 1992;8(4):46 8. 7. Zylicz Z, Krajnik M. The use of antitussive drugs in terminally ill patients. European Journal of Palliative Care 2004 NovDec; 11(6): 2259. 8. Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, et al. Diagnosis and Management of Cough Executive Summary. Chest. January 2006;129:1S 23S. 9. Holmes RL, Fadden CT. Evaluation of the Patient with Chronic Cough. American Family Physician. May 1, 2004;69(9):2159 66. 10. Whiting N. Cough. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2 nd ed. New York: Oxford University Press Inc.; 2005. 11. Sherman DW, Matzo ML, Coyne P, Ferrell BR, Penn BK. Teaching symptom management in endoflife care: the didactic content and teaching strategies based on the endoflife nursing education curriculum. Journal for Nurses in Staff Development JNSD. 2004 MayJun;20(3):10315; quiz 167. 12. Coyne PJ, Lyne ME, Watson AC. Symptom management in people with AIDS. American Journal of Nursing. 2002 Sep;102(9):4856; quiz 7. 13. Dudgeon D. Dyspnoea. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. 14. McCool FD, Rosen MJ. Nonpharmacologic Airway Clearance Therapies: ACCP EvidenceBased Clinical Practice Guidelines. Chest. January, 2006;129(Supplement):250 9. 15. Registered Nurses’ Association of Ontario. Nursing Best Practice Guideline: Nursing Care of Dyspnea: The 6th Vital Sign in Individuals with Chronic Obstructive Pulmonary Disease (COPD). Nursing Best Practice Guidelines Program 2005; Available from: http://www.rnao.org/Storage/11/604_BPG_COPD.pdf 16. Homsi J, Walsh D, Nelson KA. Important drugs for cough in advanced cancer. Support Care Cancer. 2001;19:56574. 17. Stein WM, Young KM. Nebulized morphine for paroxysmal cough and dyspnea in a nursing home resident with metastatic cancer. The American Journal of Hospice and Palliative Care. March/April 1997;14(2):52 6. 18. Moroni M, Porta C, Gualtiei G, Nastasi G, Tinelli C. Inhaled sodium cromoglycate to treat advanced lung cancer patients. British Journal of Cancer. 1996;74(2):30911. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 40 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition DEHYDRATION Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Dehydration in the last days may bring about relief from previously distressing symptoms. It has been proposed that the fluid and electrolyte imbalances of dehydration may serve as a natural anesthetic to reduce the patient’s suffering.(113) Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of dehydration in the last days. This guideline does not address disease specific approaches in the management of dehydration. Definition of Terms · · · “Withdrawing from food and fluid is a common, natural part of the dying process”.(1) Dehydration is a common condition that is associated with the following conditions; thirst, dry mouth, fatigue, constipation and decreased cognition which may not be attributable to dehydration alone. Low fluid intake has not shown to predict the severity of these symptoms.(1, 3, 5, 7, 10, 1417) Medically, dehydration is a serious and potentially lifethreatening condition in which the body contains an insufficient volume of water for normal functioning. The term “volume depletion” is similar to dehydration, but it refers to the loss of salts as well as water.(18) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment Recommendation 1 Assessment of Dehydration Ongoing comprehensive assessment is the foundation of effective dehydration management, including interview, physical assessment, medication review, medical and surgical review, psychosocial and physical environment review and appropriate diagnostics(16, 9, 1315, 17, 19, 20) (see Table 1). Document1 Page 41 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1: Dehydration Assessment using Acronym O, P, Q, R, S, T, U and V * O P When did you start to feel dehydrated? Have you experienced it before? Onset Provoking / What brings it on? What makes it better? What makes it worse? Palliating Q R What does it feel like (dry mouth / skin, thirst)? Can you describe it? Quality Region / Where is it affecting or bothering you? Radiation S T U Severity Treatment What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? Understanding/ How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Recommendation 2 Diagnosis Intervention aimed at reducing dehydration must take into account the cause (often multifactorial) of the symptom, the disease trajectory and the patient / family values and goals of care.(1, 3, 7, 1316, 1921) Document1 Page 42 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Reversible Causes of Dehydration: Nausea and / or vomiting Diarrhea Gastrointestinal Obstruction Anorexia Infection Hypercalcemia Medications – reduced intake – malabsorption – reduced intake and malabsorption – reduced intake – increases insensible losses, reduced intake – diuretics increase urinary losses *dry mouth and thirst are common side effects of medications and altering them may unmask adequate hydration NonReversible Causes of Dehydration: Terminal / endstage disease or illness Recommendation 3 Education Provide anticipatory guidance and / or education whenever possible to alleviate distress about hydration status: (1, 4, 8, 16) · · · · · · Oral intake will lessen over time related to changes in metabolism and body requirements.(35, 19) Parenteral fluid does not equal nutrition.(22) Hydration has little or no effect on sensation of thirst and dry mouth.(1, 3, 6, 9, 15, 20) Teach interventions that provide relief from thirst and / or dry mouth such as oral care, offering fluids, ice chips, chewing gum, mist or spraying mouth, lubrication of lips and skin care so family can contribute to care (if desired).(1, 5, 6, 8, 10, 12) Some situations may dictate the need for a team and family conference.(19) Resources for patients considering the benefits and burdens of parenteral hydration.(23, 24) Recommendation 4 Treatment Goal of treatment should be to conserve or restore the best quality of life. It should be made on an individual basis taking into consideration the potential risks and benefits and should be reviewed daily.(14, 711, 14, 15, 17, 19, 20, 25) Management of Dehydration · · · Good oral care should be provided by family or caregivers.(1, 8, 9, 11, 12, 15, 26) Offer oral fluids (with or without lemon), ice chips or mist / spray to hydrate oral tissues.(1, 2, 9, 26) When oral intake is severely restricted, parenteral hydration (example – hypodermoclysis) may be indicated: Document1 Page 43 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition o o o For patients in good symptom control when maintenance of cognitive status is important.(26) To avoid medication side effects such as myoclonus, discontinuing hydration once side effect resolves or the terminal phase is reached.(3) A short trial of rehydration with clear goals and time frame (48 to 72 hours) to assess relief of symptoms that may be caused by dehydration.(1, 2, 6, 10, 14, 15, 22, 25, 26) Hydration Clinical studies suggest that terminally ill cancer patients may achieve adequate hydration with much lower volumes (as low as one litre per day) than recommended for the average medical and surgical patient due to: (14, 20) · · · Decreased body weight. Decreased free water clearance. Decreased insensible water losses due to decreased physical activity. Appropriate Use of Parenteral Fluids Theoretical advantages(1, 7, 1013, 1921, 27) · · · · · · · May relieve thirst and improve oral comfort. Improved renal function will lead to increased clearance of drugs and toxic metabolites. May facilitate resolution of reversible conditions (hypercalcemia, opioid neurotoxicity). Facilitates productive cough and thereby improves clearing of secretions. Improves function of unobstructed bowel. May improve delirium and / or terminal agitation, leading to better communication with family. Satisfies family’s need to provide nourishment and “do everything that can be done”. Theoretical disadvantages(1, 7, 1013, 19, 20, 27) · · · · · · · · Oral secretions causing need for suctioning. Urine output causing bedwetting and bedpans or catheters. Respiratory tract secretions causing cough, respiratory congestion. Gastrointestinal secretions causing vomiting. Edema may contribute to pressure sores. May prolong the agonal period without prolonging life. Places physical barriers between the patient and family which can inhibit physical contact with the patient. Medicalization of dying may force the patient to be admitted to facility. Document1 Page 44 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Hypodermoclysis (HDC) – the subcutaneous administration of fluid, can be considered for rehydration. · · · Hypodermoclysis is a safe and effective way of providing parenteral hydration.(27) Criteria for selecting patients: o Unable to ingest sufficient amounts of fluid orally, is dehydrated and has distressing symptoms that may respond to hydration. (26, 2831) o Intravenous access is not required, possible or practical.(30, 31) o Patient and / or family wish patient to receive hydration by this route.(28, 29) o Patient does not require either immediate or high volume fluid replacement.(12, 29, 32, 33) o Patient does not have respiratory congestion, large ascites or extensive edema.(29) o Patient does not have coagulation problem or bleeding.(29, 30, 32, 34) Standards of Practice: o The patient will be assessed to determine whether hydration is indicated. Dehydration alone is not a sufficient reason to offer hypodermoclysis. Confusion, delirium and myoclonus are often caused by the accumulation of toxic metabolites of drugs (such as opioids) and may be improved or relieved by rehydration.(26, 32, 33) o Prior to initiation of hypodermoclysis, a discussion should take place with the patient and family / caregiver to explain the benefits and burdens of hydration, clarify expectations and delineate clear goals. If hypodermoclysis is being offered on a trial basis or for a limited time period the parameters must be explained to the patient and family and indications for discontinuing hypodermoclysis will be discussed prior to its initiation.(13, 28, 35, 36) o Hypodermoclysis can be administered as an overnight infusion(29, 36), as a bolus(19, 29,30, 36, 37) or by continuous infusion.(19, 2932, 37) o Recommended volume maximum 1 to 1.5 litres(26, 29) of an isotonic solution daily: § Normal Saline (0.9%).(19, 26, 37) § 2/3 Dextrose (5%) – 1/3 Normal Saline (0.9%).(19, 26) § D5½NS.(29, 31) § Ringers Lactate.(31) § D5W should not be used as it becomes hypotonic as the dextrose is absorbed.(32, 37) § Potassium chloride up to 40 mEq per litre may be added to the solution if hypokalemic (26, 29, 30) § Hyaluronidase is no longer felt to be justified(30) or necessary(19, 26, 36, 37) for routine bolus hydration and is no longer available in Canada. o Recommended sites for hypodermoclysis (ask patient which site is preferred); § Upper chest, back (below scapula), thigh and upper abdominal wall.(12, 3032) Document1 Page 45 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition § Do not insert needle for hypodermocyclysis into previously irradiated skin as absorption may be impaired. § For ambulatory patients consider using chest, scapular region and abdomen and for patients limited to bedrest use thighs and abdomen.(12) § Avoid anterior or lateral thigh if edema present; abdomen if ascites present; breast tissue; lateral placement near shoulder; arms (32, 34) and perineum / groin.(36) I.V. route should be limited to: 1. patients requiring I.V. for other purposes 2. situations where the subcutaneous administration of fluids is contraindicated ie.) generalized edema or coagulation disorders. (1, 7, 14) Rehydration in patients with CHF, extensive edema and hypoalbuminaemia is often harmful.(1, 7, 15, 16, 20) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews / systematic reviews, clinical trials, case studies and guidelines / protocols using dehydration terms in conjunction with palliative / hospice / end of life / dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Black F, Downing GM. Artificial Hydration and Hypodermoclysis Guideline. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. Victoria, British Columbia: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 3117. 2. Keefe FJ, Ahles TA, Sutton L, Dalton J, Baucom D, Pope MS, et al. Partnerguided cancer pain management at the end of life: A preliminary study. Journal of Pain and Symptom Management. 2005;29(3):26372. 3. Viola RA, Wells GA, Peterson J. The Effects of Fluid Status and Fluid Therapy on the Dying: A Systematic Review. Journal of Palliative Care. May 20, 1997;13(4):41 52. 4. Gray R. To Hydrate or Not to Hydrate? Nursing Times. June 9 15, 1999;95(23):36 7. 5. Ersek M. Artificial Nutrition and Hydration: Clinical Issues. Journal of Hospice and Palliative Nursing. October December 2003;5(4):221 30. 6. End of Life / Palliative Education Resource Center Medical College of Wisconsin. NonOral Hydration and Feeding in Advanced Dementia or at the End of Life. Guidelines for Physician Staff Froedtert Hospital, Milwaukee, Wisconsin; Available from: http://www.eperc.mcw.edu/Educational%20Materials/Clinical/Guidefeedingdying.pdf 7. Lanuke K, Fainsinger R, deMoissac D. Hydration Management at the End of Life. Journal of Palliative Medicine. 2004;7(2):257 63. 8. Andrews M, Bell ER, Smith S, Tischler JF, Veglia JM. Dehydration in terminally ill patients. Postgraduate Medicine. January 1993;93(1):201 8. 9. VulloNavich K, Smith S, Andrews M, Levine AM, Tischler JF, Veglia JM. Comfort and incidence of abnormal serum sodium, BUN, creatinine and osmolality in dehydration of terminal illness. The American Journal of Hospice and Palliative Care. March/April 1998;15(2):77 84. 10. Burge FI. Dehydration and provision of fluids in palliative care. Canadian Family Physician. December 1996;42:2383 8. 11. Barham D. The last 48 hours of life: a case study of symptom control for a patient taking a Buddhist approach to dying. International Journal of Palliative Nursing 2003 Jun; 9(6): 24551. 12. Donnelly M. The benefits of hypodermoclysis. Nursing Standard. 1999 September 15;13(52):445. 13. Mercadante S, Ferrera P, Girelli D, Casuccio A. Patients’ and Relatives’ Perceptions About Intravenous and Subcutaneous Hydration. Journal of Pain and Symptom Management. October 2005;30(4):354 8. Document1 Page 46 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 14. Steiner N, Bruera E. Methods of Hydration in Palliative Care Patients. Journal of Palliative Care. December 19, 1997;14(2):6 13. 15. Jackson II KC. Evidenced Based Symptom Control in Palliative Care: Nutrition and Hydration Problems in Palliative Care Patients. Evidenced Based symptom Control in Palliative Care: Systematic Reviews and Validated Clinical Practice Guidelines for 15 Common Problems in Patients with Life Limiting Disease. 2000;8(1):183 97. 16. Morita T, Tsunoda J, Inoue S, Chihara S. Perceptions and decisionmaking on rehydration of terminally ill cancer patients and family members. American Journal of Hospice and Palliative Care. May/June 1999;16(3):509 16. 17. Morita T, Hyodo I, Yoshimi T, Ikenaga M, Tamura Y, Yoshizawa A, et al. Artificial Hydration Therapy, Laboratory Findings, and Fluid Balance in Terminally Ill Patients with Abdominal Malignancies. Journal of Pain and Symptom Management. February 2006;31(2):130 9. 18. Wikipedia. Dehydration definition. 2006 August 9th, 2006; Available from: http://en.wikipedia.org/wiki/Dehydration 19. Fainsinger R. Dehydration. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. 20. Bruera E, Neumann CM. Management of specific symptom complexes in patients receiving palliative care. CMAJ: Canadian Medical Association Journal 1998 Jun 30; 158(13): 171726. 21. Lanuke K. Hydration Management in Palliative Care Settings A survey of Experts. Journal of Palliative Care. Winter 2003;19(4):278 9. 22. Yeomans WR. Hydration and Nutrition in Palliative Care. The Canadian Journal of CME. September 1997:111 5. 23. Bailey T, Husney A, Byock I. Should I receive artificial hydration and nutrition? October 20th, 2004; Available from: http://bchealthguide.org/kbase/dp/topic/tu4431/dp.htm 24. American Academy of Family Physicians. Hypodermoclysis: A Way to Replace Lost Fluids. American Family Physician Information from Your Family Doctor November 1, 2001; Patient education pamphlet]. Available from: http://www.aafp.org/afp/20011101/hypoph.ht mL 25. Fainsinger R. Nonoral Hydration in Palliative Care #133. Journal of Palliative Medicine. 2006;9(1):2067. 26. Waller A, Caroline NL. Nutrition and Hydration: Hydration of the Terminally Ill Patient Near the End of Life. Handbook of Palliative Care in Cancer. 2nd ed. Boston: Butterworth Heinemann; 2000. p. 704. 27. Fainsinger R, Bruera E. When to treat dehydration in a terminally ill patient? Support Care Cancer. 1997;5:2005 211. 28. Claisse L. The use of hypodermoclysis in palliative care. European Journal of Palliative Care: the Journal of the European Association for Palliative Care. 2005 November December;12(6):2436. 29. Sasson M, Shvartzman P. Hypodermoclysis: An Alternative Infusion Technique. American Family Physician. November 1, 2001;64(9):1575 8. 30. Frisoli A, de Paula AP, Feldman D, Nasri F. Subcutaneous Hydration By Hypodermoclysis. Drugs and Aging. April 2000;16(4):33119. 31. Hays H. Hypodermoclysis for Symptom Control in Terminal Care. Canadian Family Physician. 1985 June;31:12536. 32. Brown MK. Hypodermoclysis: Another way to replace fluids. Nursing 2000. 2000 May;30(5):589. 33. Barton A, Fuller R, Dudley N. Using subcutaneous fluids to rehydrate older people: Current practices and future challenges. Quarterly Journal of Medicine. 2004;97(11):7658. 34. Capital Health Regional Palliative Care Program. Hypodermoclysis (HDC) Administration Protocol for Palliative CarePatients.2003October24,2005.Availablefrom:http://www.palliative.org/PC/ClinicalInfo/Clinical%20Practice%20Gu idelines/PDF%20files/3A7%20Hypodermoclysis%20Admin%20Protocol%20for%20PC%20Patients.pdf 35. McAulay D. Dehydration in the terminally ill patient. Nursing Standard. 2001 October 10;16(4):337. 36. Bruera E, Neumann CM, Pituskin E, Calder K, Hanson J. A randomized controlled trial of local injections of hyaluronidase versus placebo in cancer patients receiving subcutaneous hydration. Annals Of Oncology. August 4th, 1999;10:12558. 37. Fainsinger R. Nonoral Hydration Techniques in Palliative Care #134. Journal of Palliative Medicine. 2006;9(1):2078. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 47 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition DELIRIUM / RESTLESSNES Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptoms of delirium or restlessness. This guideline does not address disease specific approaches in the management of delirium or restlessness. Delirium occurs in approximately 30% of palliative care patients(1) and 40% of advanced cancer patients.(2) Terminal delirium reported in 88% of deaths.(3) Terminal restlessness occurs in approximately 42% to 62% of dying patients.(4, 5) Definition of Terms Delirium has been defined as a transient organic brain syndrome characterized by the acute onset of disordered attention and cognition, accompanied by disturbances of cognition, psychomotor behaviour and perception.(1) Types of Delirium: · Hypoalert – hypoactive(1, 3, 5, 6) often misdiagnosed as depression in the elderly.(1, 6 10) · · Hyperalert – hyperactive.(3, 5, 810) Mixed type – with fluctuations from hypoalert to hyperalert.(5, 6, 8, 9) Restlessness can be defined as an inability to relax or be still, the quality of being ceaselessly moving or active or a feeling of agitation expressed in motion.(3) Terminal restlessness is best described as “agitated delirium in a dying patient, frequently associated with impaired consciousness” and nonpurposeful movement.(9) Confusion, altered mental state, cognitive impairment, acute brain syndrome, restlessness, dementia and delirium are often used interchangeably – although they have different meanings.(3) Standard of Care 1. Assessment 2. Diagnosis 3. Education Document1 Page 48 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Assessment of Delerium / Restlessness Ongoing comprehensive assessment is the foundation of effective management of delirium or restlessness including interview with patient and caregiver, physical assessment, medication review, medical and surgical review, psychosocial review, review of physical environment and appropriate diagnostics (see Table 1). Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family. Table 1: Delirium/Restlessness Assessment using Acronym O,P Q,R,S,T,U and V * O P When did it begin? How long does it last? How often does it occur? Onset Provoking / What brings it on? What makes it better? What makes it worse? Is it constant or variable? Is it progressive? Palliating Q R Quality Region / What does it feel like? Do you feel confused? Are you seeing or hearing anything unusual? How are you sleeping? Do you know what day/month/year it is? Do you know where you are right now? Can you tell me your full name? Describe the change you see in his/her thinking? Radiation S T U Severity Treatment Understanding/ What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Document1 Page 49 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Onset: · · Has an acute onset.(1, 7, 11, 12) Can fluctuate and be preceded by subtle changes.(3, 5, 7, 13) Signs and Symptoms of Delirium: · · · · · · · Affected reasoning – irrelevant or rambling thinking, abnormal conceptualization and altered insight with anosognosia (unawareness or denial of neurological deficit).(2, 6, 13, 14) Agitation.(1, 6, 7, 11, 13, 15) Altered level of consciousness.(1, 57) or sleep – wake cycle (reversal, shorter, longer).(3, 57, 11, 15) Anger.(1, 3, 5, 6, 11, 16) Anxiety.(13, 5, 6, 13, 14, 16) Attention disturbances.(1, 5, 7) Delusions – poorly organized and characterized by paranoid features.(3, 5, 6, 8, 1114, 16) · · · · · · · · · · · · · · · Depression.(1, 3, 6, 13, 14, 16) Disorientation to time, as well as place and person (in more severe cases).(1, 5, 7, 13) Emotionally labile.(1, 5, 6, 13) Enhanced startle reflex.(3) Hallucinations(5, 6, 8, 11, 12, 17) often visual(1, 6, 13) or tactile but less often auditory (this is more common with schizophrenia).(1, 3, 6, 16) Irritability.(5, 6, 13) Language abnormalities – lack fluency and spontaneity, conversation may be prolonged and interrupted by long pauses or repetitions, inability to find the correct word. Writing abilities are affected early and more severely than other language related skills.(6, 7, 13, 14, 16) Lethargy.(1, 16) Memory impairment.(1) Mydriasis – occurs with anticholinergic toxicity.(3) Myoclonus.(1, 5, 6, 11, 13, 15, 16) Nightmares.(1, 17) Restlessness.(1, 5, 6, 11, 15) Seizures.(11, 15) Tremors – typical in alcohol withdrawal.(3, 5, 6) Delirium is more likely to be more reversible on first occurrence, less so with second and subsequent occurrences.(1,6,13) Reversal of delirium is possible in approximately 56% of first episodes, but only 26% if a subsequent delirium developed.(3) Factors associated with irreversible delirium are: hypoxic encephalopathy, metabolic factors (hypercalcemia, hyponatremia, renal insufficiency) or nonrespiratory infection.(2) Delirium may not be reversible in the last 24 to 48 hours of life.(7, 18) Document1 Page 50 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Laboratory Studies: Depending on the clinical situation the following tests may be indicated: WBC, serum electrolytes (Na, K, Mg, PO4, Ca, Cl), urea, creatinine, creatinine clearance, glucose, liver function tests, ammonia, thyroid hormone, TSH, adrenal function, blood and urine cultures, blood gases, pulse oximetry.(3, 5, 7) Recommendation 2 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. The most significant intervention in the management of delirium or restlessness is identifying underlying cause(s) and treating as appropriate. While underlying cause(s) may be evident, treatment may not be indicated, depending on the stage of the disease. Whether or not the underlying cause(s) can be relieved or treated, all patients will benefit from management of the symptom using education or medications. Identifying the underlying etiology of the delirium or restlessness is essential in determining the interventions required. Underdiagnosing is a problem in delirium.(13, 5, 7) The decision to carry out investigations must be weighed against the value which will be gained from the results and the expected improvement from treatment based on those tests, as well as the morbidity and ‘usefulness’ of pursuing investigations in a patient who may be deteriorating quickly and close to death.(2, 3, 5) A number of assessment tools exist to assist in assessment of delirium.(6, 7) DSM IV criteria for diagnosing delirium due to a general medical condition:(2, 5, 13, 14, 16) · · · · Disturbance of consciousness with reduced ability to focus, sustain and shift attention. Change in cognition (such as memory deficit, disorientation, language disturbances or perception disturbances not better explained by a preexisting stabilized or evolving dementia). The disturbance develops over a short period of time and tends to fluctuate during the course of the day. There is evidence from the history, physical examination or laboratory findings that the disturbance is caused by the direct physiological consequences of a general medical condition. Causes of Delirium: usually multifactorial(5, 6, 8, 11) · Neoplastic o Primary tumour of brain.(6, 11, 13) o Metastases.(1, 6, 11, 13) o Tumour burden or location.(3) Document1 Page 51 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · Infection/inflammatory – pneumonia and urinary tract infection(13, 6, 7, 10, 1214, 16, 18), other causes of sepsis. Metabolic – hypercalcemia, uremia, hypoglycemia, hyperglycemia, or hyponatremia. (1, 3, 7, 10, 11, 13, 14, 16) Drug Effects o Idiosyncratic: § Anticholinergic drugs.(6, 11, 13) § Anticonvulsants.(18) § Antidepressants. § Antiemetics.(6, 13) § Antihypertensives.(6, 13) § Antiviral.(6, 7, 13) § Chemotherapy – vinca alkaloids, methotrexate, cisplatin, bleomycin, procarbazine. (11, 13, 18) § Corticosteroids.(1) § H2 antagonists.(1, 3, 6, 13, 18) § Neuroleptics.(3) § Opioids.(3, 11, 15) o Overdosage § Due to physical deterioration.(3) § Due to metabolic causes.(1, 3) § Accidental.(3, 13, 16) § Intentional – alcohol or drug intoxication.(3, 18) o Drug Withdrawal § Alcohol.(16) § Barbiturates. § Benzodiazepines.(3, 18) § Nicotine.(3) § Opioids.(1, 2, 6, 13) § Steroids.(1, 6) · Cardiopulmonary – cerebral hypoxia, hypercapnia, or cerebrovascular disease.(3, 10) · Discomfort – pain, constipation, urinary retention, or dehydration.(1, 6, 7, 1113, 16, 19) · · · · Endocrine dysfunction – thyroid and adrenal. (1, 6, 7, 13, 18) Liver failure.(6, 11, 14, 18) Malnutrition – thiamine or folate or vitamin B12.(13, 6, 7, 13, 16) Psychosocial or Psychiatric Causes: grief (18), sensory deprivation(7) or overload (7) or social isolation.(7) · Renal failure.(1, 11, 13, 15, 19) · Trauma – convulsion, subdural hematoma, or hemorrhage.(13, 13, 16, 18) · Visual or hearing impairment.(18) Document1 Page 52 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Causes Contributing to Restlessness: Physical – pain, constipation, bladder retention, hypoxia, metabolic, organ failure, fever.(3, 4) Drug effect – Extrapyramidal effects, akathisia, opioidinduced neurotoxicity.(3) Psychosocial – personal suffering, existential anguish, interpersonal conflict, spiritual journey, worry, grief.(3, 4) Psychiatric – delirium of any cause, dementia, anxiety disorder.(1, 6, 13) Imminently dying – any combination of above with altered, fluctuating and declining state of consciousness.(3, 13, 16) Recommendation 3 · · Education It is important to explain to the family that the symptoms are caused by the illness, are not within the patient’s control, will fluctuate(1, 2, 6, 7, 13, 14, 16) and the patient is not going ‘insane’.(13, 14) Include the family in decision making, emphasizing the shared goals of care.(14) Report hallucinations that become threatening.(12) Patients may have comforting hallucinations – common in hypoactive delirium.(3, 13) · · Instruct the family to provide gentle, repeated reassurance(3, 7, 13) and avoid arguing with the patient.(2, 3, 13, 16) encourage the family to be present in a calming way.(2, 4) Recommendation 4 · · · · · · · · Treatment: Nonpharmacological Watch for the sun downing effect (nocturnal confusion)(13, 6, 13, 14, 16) as it is often the first symptom of early delirium.(2, 3, 6, 18) Provide a calm, quiet environment and help the patient reorient to time, place and person (visible clock, calendar, well known object).(5, 6, 14, 18) Presence of a well known family member is preferred.(46, 13) Provide a well lit, quiet environment.(27, 13, 14, 16) Provide night light.(1) Keep visitors to a minimum to prevent over stimulation(1, 13) and minimal staff changes(13) and room changes.(7) Correct reversible factors – dehydration(6, 11, 19) nutrition(11) alteration in visual or auditory acuity (provide aids)(5, 18) sleep deprivation.(3, 7) Avoid the use of physical restraints, catheterization or other impediments to ambulation.(3) Encourage activity if patient is physically able.(13) When Mildly Restless Provide: · Observation(3, 5) and relaxation techniques (massage, tub baths, gentle music) as applicable.(14) Document1 Page 53 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 5 · · · · · · Pharmacological Correct reversible factors – infection, constipation, pain, withdrawal, drug toxicity.(10, 13) A firm diagnosis may only be attainable in less than half of cases.(13) Review medications; consider opioid rotation to reverse neurotoxicity,(1, 2, 8, 13) discontinue unnecessary drugs or prolong the dosing interval for necessary drugs.(3) Hydration may accelerate clearance of metabolites involved in opioid neurotoxicity. If a patient is developing sun downing effect (confusion in the evening),(11) psychotropic drugs have a place in treatment. Anticipate the need to change treatment options if agitation develops – particularly in cases where patient, family and staff safety may become threatened.(5, 18) Benzodiazepines may paradoxically excite some patients(10, 15) and should be avoided unless the source of delirium is alcohol or sedative drug withdrawal, or when severe agitation is not controlled by the neuroleptic.(10) Examples of neuroleptic drugs include haloperidol and methotrimeprazine. If patient has known or suspected brain metastases a trial of corticosteroids is worthwhile.(6) Dexamethasone 16 to 36 mg PO daily in the morning (6) or divided b.i.d. Medication Used for Mild Restlessness · · Haloperidol 0.5 to 1.5 mg PO t.i.d.(3) The parenteral dose should be 50% of the oral dose.(3, 5) Lorazepam 1 to 2 mg S.C. should be used as an adjunct only on a p.r.n basis only until the neuroleptic provides control.(3) Medication Used for Delirium and Agitation In Terminal Illness · Restless & Confused but Cooperative • Haloperidol 1.5 to 5 mg PO or S.C. q4h to q8h.(3) • Methotrimeprazine 10 to 15 mg for mild and up to 50 mg for severe delirium PO or SL or SC q4h to q6h.(3) · Delirium with Paranoia, Confusion and/or Aggression • Haloperidol 510 mg S.C. or I.V. q30 to 60 min until relief then maintenance dose is 50% of amount to achieve control (usually between 1.5 to 20 mg per day divided into one to three doses).(3) OR • Methotrimeprazine 10 to 50 mg S.C. q30min until relief then 10 to 50 mg PO or SL or S.C. q4h to q8h.(3) OR • Chlorpromazine 50 to 100 mg I.M. or rectally or I.V. q1h until relief then 12.5 to 50 mg PO or I.V. q4h to q12h.(4) Document1 Page 54 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Consider palliative sedation when all other measures have failed.(18) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using delirium/restlessness terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Caraceni A, Martini C, Simonetti F. Neurological problems in advanced cancer. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 70326. 2. Lawlor PG, Gagnon B, Falconer W. Cognitive impairment. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. p. 295307. 3. Downing GM. Neurological Confusion: Delirium and Dementia and Restlessness. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 45563. 4. March PA. Terminal restlessness. The American Journal of Hospice and Palliative Care. 1998 January February;15(1):513. 5. Breitbart WS, Strout D. Delirium in the Terminally Ill. Clinics in Geriatric Medicine. 2000;16(2):35772. 6. Friedlander MM, Brayman Y, Breitbart WS. Delirium in Palliative Care. Oncology. 2004 October;18(12):154153. 7. Brown S, Degner LF. Delirium in the terminallyill cancer patient: aetiology, symptoms and management. International Journal of Palliative Nursing. 2001;7(6):2668, 7072. 8. Plonk WM, Arnold R. Terminal Care: The Last Weeks of Life. Journal of Palliative Medicine. 2005;8(5):104254. 9. Kehl KA. Treatment of Terminal Restlessness: A Review of the Evidence. Journal of Pain & Palliative Care Pharmacology. 2004;18(1):530. 10. Quijada E, Billings A. Pharmacologic Management of Delirium; Update on Newer Agents. 2002 January; Available from: http:// www.aahpm.org/cgibin/wkcgi/view?status=A%20&search=944&id=297&offset=100&limit=25 11. Doorley J, McNeal W. The Role of Neuroleptics in Managing Morphineinduced Terminal Delirium. Clinical Nurse Specialist: The Journal for Advanced Nursing Practice. 2004;18(4):1835. 12. Calne S, Kumar A. Nursing Care of Patients with LateStage Parkinson’s Disease. Journal of Neuroscience Nursing. 2003 October;35(5):24251. 13. Waller A, Caroline NL. Confusional States. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA: Butterworth Heinemann; 2000. p. 30917. 14. Paolini CA. Symptoms Management at the End of Life. The Journal of the American Osteopathic Association. October 2001;101(10):609 15. 15. Ferris FD, et al. Competency in EndofLife Care: Last Hours of Life. Journal of Palliative Medicine. 2003;6(4):60513. 16. Dean M, Harris JD, Regnard C, Hockley J. Confusional states (delirium and dementia). Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 1716. 17. Confusion definition. 2006 September 2nd, 2006; Available from: http://en.wikipedia.org/wiki/Confusion 18. Ross DD, Alexander CS. Management of Common Symptoms in Terminally Ill Patients: Part II Constipation, Delirium and Dyspnea. American Family Physician. September 15, 2001;64(6):1019 26. 19. Esper P, Heidrich D. Symptom Clusters in Advanced Illness. Seminars in Oncology Nursing. February 2005;21(1):20 8. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 55 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition DEPRESSION IN THE TERMINALLY ILL Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health , British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of depression. This guideline does not address disease specific approaches in the management of depression.(112) Definition of Terms Depression is a primary mood disorder which, according to the DSMIVTR includes: · a depressed mood and/or · an inability to experience pleasure in normally pleasurable acts (anhedonia).(13) For major depression, the DSMIVTR states that one of the above symptoms must be present for a period of at least two weeks in combination with four or more of the following symptoms:(13) · Feelings of overwhelming sadness and/or fear, or the seeming inability to feel emotion (emptiness). · A decrease in the amount of interest or pleasure in all, or almost all, daily activities. · Changing appetite and marked weight gain or loss. Note: ensure not related to disease process. · Disturbed sleep patterns, such as insomnia, loss of rapid eye movement (REM) sleep, or excessive sleep (hypersomnia). · Psychomotor agitation or retardation nearly every day. · Fatigue, mental or physical, also loss of energy. · Intense feelings of guilt, helplessness, hopelessness, worthlessness, isolation/loneliness and/or anxiety. · Trouble concentrating, keeping focus or making decisions or a generalized slowing and obtunding (to dull or blunt, especially sensation or pain) of cognition, including memory. · Recurrent thoughts of death (not just fear of dying), desire to just “lay down and die” or “stop breathing”, recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide. · Feeling and/or fear of being abandoned by those close to one. Document1 Page 56 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Minor depression is a lessused term for a subclinical depression that does not meet criteria for major depression but where there are at least two symptoms present for two weeks. Note: do not include symptoms that are clearly due to a general medical condition, or moodincongruent delusions or hallucinations. Standard of Care 1. Incidence and Risk Factors 2. Assessment 3. Diagnosis 4. Education 5. Treatment: Nonpharmacological 6. Treatment: Pharmacological Recommendation 1 Incidence and Risk Factors Incidence and Risk Factors People with advanced illness have a higher incidence of clinical depression than the general population. The prevalence of depression in the general population is 6 to 10%.(9) Terminally ill patients have been found to have a higher level of both physical and emotional distress with 24% having depression.(14) Clinical depression occurs in 15 to 30 % of cancer patients. The diagnosis of depression in people with cancer is often underdiagnosed and undertreated.(9) Risk factors include: Noncancer related risk factors: • History of depression or family history of depression.(3, 4, 9, 10) • Two or more episodes in a lifetime. • First episode early or late in life. • Lack of family or social support.(8, 10) • Previous suicide attempts.(3, 4, 9) • Concurrent chronic illnesses such as: stroke or myocardial infarction.(15) • Intercurrent substance abuse Cancerrelated risk factors: • Depression at time of cancer diagnosis.(3, 4) • Advanced stage of cancer.(4, 9, 10) • Additional concurrent life stressors.(3, 4, 9) • Increased physical impairment or discomfort.(4, 5, 810, 12) • Being unmarried and having head and neck cancer.(10) • Pancreatic and primary or metastatic brain cancers.(4, 8, 10) Document1 Page 57 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · Medications may contribute to depression (benzodiazepines, corticosteroids, anticonvulsants, methyldopa, propranolol, chemotherapeutic agents).(4, 7, 8, 10) Chronic pain.(3,4,8,9,10,12) Recommendation 2 Assessment of Depression Ongoing comprehensive assessment is the foundation of effective management of depression, including interview, physical assessment, medication review, medical and surgical review, psychosocial review, review of physical environment and appropriate diagnostics. Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family.(1, 2, 5, 16) Recognition and diagnosis of depression is variable depending on the clinical setting and the diagnostic acumen of those delivering end of life care.(9) Suggested Questions for the Assessment of Depressive Symptoms in Adults with Terminal Illness(15, 17) How well are you coping with your illness. Well? Poor? Well being How are your spirits since diagnosis? During treatment? Down? Blue? Mood Do you cry sometimes? How often? Only alone? Mood Are there things your still enjoy doing, or have you lost pleasure in things you used to do before you became ill? Anhedonia How does the future look to you? Bright? Black? Hopelessness Do you feel you can influence your care, or is your care totally under others’ control? Helplessness Do you worry about being a burden to family and friends during the treatment? Worthlessness Physical symptoms (Evaluate in the context of disease related symptoms) Do you have pain that is not controlled? Pain How much time do you spend in bed? Fatigue Do you feel weak? Fatigue easily? Rested after sleep? Any relationship between how you feel and a change in treatment or how you otherwise feel physically? Fatigue How is your sleeping? Trouble going to sleep? Awake early? Often? Insomnia How is your appetite? Food tastes good? Weight loss or gain? Appetite How is your interest in sex? Extent of sexual activity? Libido Do you think or move more slowly than usual? Psychomotor slowing Adapted from Roth, AJ, Holland JC: Psychiatric complications in cancer patient. In: Brain MC, Carbone PP, eds.: Current Therapy in HematologyOncology. 5th ed. St Louis, Mo: MosbyYear Book, Inc., 1995, pp 609618. Document1 Page 58 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Mnemonics commonly used to remember the DSMIV criteria are: · · SIGECAPS (sleep, interest (anhedonia), guilt, energy, concentration, appetite, psychomotor, suicidality)(17) and DEAD SWAMP (depressed mood, energy, anhedonia, death (thoughts of), sleep, worthlessness/guilt, appetite, mentation, psychomotor).(17) Recommendation 3 Diagnosis Identifying the underlying etiology of depression is helpful in determining the interventions required. The usual somatic symptoms of depressed patients (fatigue, loss of appetite, sleep disturbance, poor concentration, etc.) are often present in advanced cancer and terminal illness and cannot always be relied upon for diagnosis.(4, 10) Psychological symptoms of depression that are persistent, out of character and severe are of greater diagnostic value in patients with advanced illness.(5, 18) In particular, watch for pervasive dysphoria, feelings of helplessness, hopelessness and worthlessness, guilt, loss of selfesteem, loss of interest and wishes to die. Even very mild or passive suicidal ideation is indicative of significant depression in terminally ill patients.(1, 46) If the diagnosis of depression is uncertain, consider psychiatric referral and a trial of antidepressant medication or therapy. When in doubt, treat.(1, 6) Recommendation 4 Education Depression is a distressing symptom to experience and witness. It is commonly under reported as many of the signs and symptoms are a feature of terminal illness.(1, 5) Reinforce to patient and family the importance of reporting symptoms that are causing distress, physical or psychological, as both may influence psychological well being.(1, 5, 9) Reinforce that if depression is diagnosed it can be managed. Treatment can be effective even when life expectancy is short.(1, 5, 9) Teach the purpose of Nonpharmacological and pharmacological measures and the goal of each.(5) Teach that many antidepressant medications take time to become effective.(5) Recommendation 5 Treatment: Nonpharmacological Depression in patients with advanced disease is optimally managed by utilizing a combination of supportive psychotherapy, cognitivebehavioural techniques, and antidepressant medications.(8, 12) Document1 Page 59 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Always ensure that pain is well treated or alleviated. Uncontrolled pain is a major risk factor for depression and suicide among patients with cancer.(1, 2, 4) For patient and family consider psychosocial therapies, relaxation techniques, massage therapy and therapeutic touch.(1, 46, 8, 12, 15) Recommendation 6 Treatment: Pharmacological “Medication without ongoing contact is often seen as abandonment and never acceptable.”(19) · · · · · Start with low doses and increase slowly.(1, 5, 6, 8, 15) When anticipated survival time is short, consider psychostimulants due to their more immediate onset of effect.(1, 5, 6, 8, 15) Consider side effects and additional therapeutic benefit (tricyclic antidepressants may benefit neuropathic pain but worsen constipation; avoid tricyclics in patients with cardiac conduction delays, etc.).(1, 2, 5, 6, 8, 15) Withdrawal symptoms may be of significant importance in palliative patients who are unable to continue with oral medications. There are similar response rates when comparing antidepressant medications.(20) Selective Serotonin Reuptake Inhibitors (SSRIs):(1, 2, 5, 8, 10, 15) Example: Citalopram,(6) Paroxetine, Fluoxetine, Sertraline(15) Initial and maintenance doses are specific for each of the SSRI’s. Initial dose for Citalopram: 10 to 20 mg per day to start, increasing at intervals of no less than one week. Maximum daily dose is 60 mg, although doses above 40 mg are not ordinarily recommended.(20) Usual maintenance dose is 20 to 30 mg per day. · · · · Have fewer side effects than tricyclic antidepressants (TCAs). Start SSRI at half the usual dose for the general population. Paroxetine and fluoxetine are active inhibitors of the enzyme responsible for metabolizing oxycodone and codeine to its active analgesic form. Concurrent use of these opioids and SSRIs can therefore result in decreased pain control. The sudden cessation of SSRI therapy when a patient is unable to swallow can produce a withdrawal syndrome. Withdrawal risk is greater with shorthalf life drugs such as paroxetine, lowest with longhalf life drugs such as fluoxetine, and are of intermediate risk for other SSRI’s.(20) Fluoxetine has less selective receptor sites and a much longer halflife than the other SSRIs and should not be the drug of choice. Switching to other antidepressants after having been on fluoxetine can be complicated due to the extended half life.(5) Document1 Page 60 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition SerotoninNorepinephrine Reuptake Inhibitors (SNRIs): Example: Venlafaxine(10) Initial dose: Venlafaxine XR – 37.575 mg per day then maintenance dose: 150 to 375 mg per day. Atypical Antidepressants: Example: Bupropion(1, 2, 8, 15) · Initial activating doserelated seizureinducing potential. Contraindicated in patients with a history of seizure, in those with concomitant conditions predisposing to seizure, and in patients taking other drugs that lower seizure threshold. · Low incidence of sedative, hypotension and anticholinergic side effects. · Can cause over stimulation. · Generally considered third line treatment. · Initial: 100 mg per day then maintenance: 200300 mg per day. Example: Trazodone(1, 10) · Trazodone may cause hypotension including orthostatic hypotension and syncope; caution is required if it is given to patients receiving antihypertensive drugs and an adjustment in the dose of the antihypertensive medication may be required · Increased serum digoxin and phenytoin levels have been reported with concurrent trazodone use.(1,10) · Treatment should be started with low initial doses of 25 to 50 mg daily in divided doses or in an evening single dose. The dose may be increased slowly to a maximum of 300400 mg daily in ambulatory patients and to 600 mg daily in hospitalized patients. Example: Mirtazapine(10, 21) · A tetracyclic antidepressant. Mirtazapine elimination is decreased in elderly persons. · When used concomitantly with drugs that reduce the seizure threshold (e.g., phenothiazines), mirtazapine may increase the risk of seizure. · Initial dose: 7.5 to 15 mg daily, maintenance dose: 15 to 45 mg daily. Psychostimulants:(1, 2, 5, 10, 12) Examples: Methylphenidate and Dextroamphetamine. · Consider this class of medication when life expectancy may be short,(1, 5, 6, 8, 15) as these drugs work within hours to days. · They often enhance opioid analgesia, reduce opioid sedation and improve appetite. They can improve attention, concentration and overall performance. · Side effects include agitation, confusion, insomnia, anxiety and paranoia. Use cautiously in the elderly, avoid in delirious patients(1) and underlying medical conditions that may be compromised by increases in blood pressure or heart rate Document1 Page 61 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · such as preexisting hypertension, heart failure, recent myocardial infarction, or hyperthyroidism.(21) A common clinical practice is to start a psychostimulant and a SSRI together and then withdraw the stimulant while titrating the SSRI upward. Start methylphenidate at 5 mg PO at 8 AM and noon. Initial doses could be lower at 2.5 mg b.i.d. in very frail patients. Increase 2.5 to 5 mg every 1 or 2 days until desired effect is reached, or to a maximum daily dose of 30 mg per day.(23) Afternoon dosing can affect nighttime sleep and is generally not recommended.(5) Tricyclic Antidepressants (TCA)(1, 2, 5, 8, 10, 15) Examples: Nortriptyline, Amitriptyline, Desipramine, Imipramine and Doxepin · Requires a careful riskbenefit ratio analysis because the adverse effect profile may be troubling to patients in a palliative/hospice setting.(1) Effects include sedation and anticholinergic effects; dry mouth, blurred vision, urinary hesitancy, or retention, constipation. · Avoid TCA’s in patients with cardiac conduction delays,(1, 2, 5, 6, 8, 15) coronary artery disease, or history of myocardial infarction in past six months.(20) · Adverse effects usually decrease 3 to 4 days after initiation of a TCA or after increasing the dosage. · The secondary amines (desipramine and nortriptyline) generally have fewer side effects, such as sedation and anticholinergic effects, than the tertiary amines (imipramine, amitriptyline, and doxepin).(23) · The specific liver enzyme cytochrome P450 metabolism pathway may affect drug levels. From 5 to 10% of Caucasians have a recessive gene that results in deficient 2D6 metabolism which would affect desipramine and nortriptyline.(20) Twenty percent of Asians are deficit in the 2C19 enzyme affecting the metabolism of TCA’s such as imipramine.(20) · Start at low doses (10 to 25 mg PO at bedtime) and increase by 10 to 25 mg PO every 4 days. · Onset of antidepressant effect may take 2 to 4 weeks. · May provide additional neuropathic pain benefits. References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane, DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using depression terms in conjunction with palliative/hospice/end of life/dying/ terminally ill. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Billings JA. Depression. Journal of Palliative Care. 1995 Spring;11(1):4854. 2. Block SD, Panel for the ACP ASIM EndofLife Care Concensus. Assessing and managing depression in the terminally ill patient. Annals of Internal Medicine. 2000;132(3):20918. 3. Durkin I, Kearney M, O’Siorain L. Psychiatric disorder in a palliative care unit. Palliative Medicine. 2003;17(2):212 8. Document1 Page 62 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 4. Gibson C, Lichtenthal W, Berg A, Breitbart WS. Psychologic issues in palliative care. Anesthesiology Clinics of North America. 2006;24(1):6180. 5. Goldberg L. Psychologic issues in palliative care: Depression, anxiety, agitation and delirium. Clinics in Family Practice. 2004;6(2):44170. 6. Goy E, Ganzini I. Endoflife care in geriatric psychiatry. Clinics in Geriatric Medicine. 2003;19:84156. 7. Jefford M, Mileshkin L, Richards K, Thomson J, Zalcberg.J., al E. Rapid screening for depressionvalidation of the brief casefind for depression (BCD) in medical oncology and palliative care patients. British Journal of Cancer. 2004;91(900906). 8. Lander M, Wilson K, Chochinov HM. Depression and the dying older patient. Clinics in Geriatric Medicine. 2000;16(2):33556. 9. LloydWilliams M. Screening for depression in palliative care patients: A review. European Journal of Cancer Care. 2001;10(1):315. 10. Potash M, Breitbart WS. Affective disorders in advanced cancer. Hematology Oncology Clinics of North America. 2002 June;16:671700. 11. Slaughter J, Beck D, Johnston S, Holmes S, McDonald A. Anticipatory grief and depression in terminal illness. Annals of Long Term Care. 1999;7(8):299304. 12. Stiefel R, DieTrill M, Berney A, Olarte JMN, Razavi D. Depression in palliative care: A pragmatic report from the Expert Working Group of the European Association for Palliative Care. Supportive Care in Cancer. 2001 October;9(7):47788. 13. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders IVTR. 5th ed. Washington, D.C.: American Psychiatric Association,; 2000. 14. LloydWilliams M, Friedman T. Depression in palliative care patients a prospective study. European Journal of Cancer Care. 2001;10:2704. 15. Roth AJ, Holland JC. Psychiatric complications in cancer patients. In: Brain MC, Carbone PP, editors. Current Therapy in Hematology Oncology. 5th ed. St. Louis: Mosby Year Book Inc.; 1995. p. 60918. 16. Wilson KG, Graham ID, Viola R, Chater S, Faye BJ, Weaver LA, et al. Structured interview assessment of symptoms and concerns in palliative care. Canadian Journal of Psychiatry. 2004;49(6):3508. 17. Clinical Depression Mnemonics. 2006 November 9th; Available from: http://en.wikipedia.org/wiki/Clinical_ depression#Mnemonics 18. Calne S, Kumar A. Nursing Care of Patients with LateStage Parkinson’s Disease. Journal of Neuroscience Nursing. 2003 October;35(5):24251. 19. Thompson M, Wainwright W. Psychosocial Care. In: Downing GM, Wainwright W, editors. Medical Care of the th Dying. 4 ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 53569. 20. Gold Standard I. Citalopram, Clinical Pharmacology (database online). 2006 [cited 2006 November 22]; Available from:http://www.clinicalpharmacology.com/ 21. Mirtazapine. 2006 November 9, 2006 [cited; Available from: http://en.wikipedia.org/wiki/Mirtazapine#Dosage 22. Downing GM. Neurological Depression. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 4646. 23. Lacy CF, Armstrong LL, Ingrim NB, Lance LL. Drug Information Handbook Pocket 199899. Hudson, Ohio: Lexi Comp Inc; 1998 p.1364 Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 63 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition DYSPNEA Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice settings in which a user may see the guidelines as applicable. Up to 95% of COPD patients, 78.6% of advanced cancer patients and 75% of patients with advanced disease of any cause experience dyspnea.(110) Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of dyspnea. This guideline does not address disease specific approaches in the management of dyspnea. Definition of Terms Dyspnea (shortness of breath) is a term used to characterize a subjective experience of breathing discomfort that consists of qualitative distinct sensations that vary in intensity. The experience derives from interactions among multiple physiological, psychological, social and environmental factors, and may induce secondary behavioural responses.(10), (120) Dyspnea may or may not be associated with hypoxemia, tachypnea or orthopnea. Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological 6. Crisis Intervention Recommendation 1 Assessment of Dyspnea Ongoing comprehensive assessment is the foundation of effective dyspnea management, including interview (see Table 1), physical assessment, appropriate diagnostics, medication review, medical and surgical review, psychosocial review and review of physical environment. Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family.(13, 9, 10, 12, 14, 19, 2125) Because dyspnea is subjective, the patient’s self report of symptoms should be acknowledged and accepted. Use a numeric rating scale (NRS) or visual analog scale Document1 Page 64 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition (VAS) for dyspnea to rate shortness of breath from 0 to 10, with 0 being no shortness of breath and 10 being shortness of breath as bad as can be.(14, 8, 10, 12, 15, 17, 19, 20, 23, 24, 2628) Table 1: Dyspnea Assessment using Acronym O, P, Q, R, S, T, U and V * O P Onset Provoking / When did it begin? How long does it last? How often does it occur? What time of day does it occur? What brings it on? What makes it better? What makes it worse? What positions are worse? Palliating Q R What does it feel like? Can you describe it? Quality Region / Where is it ? Does your throat or chest feel tight? Radiation S T U Severity Treatment Understanding/ What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? How is this symptom affecting you? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Recommendation 2 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. The most significant intervention in the management of dyspnea is identifying underlying cause(s) and treating as appropriate (see Table 2). While underlying cause(s) may be evident, treatment may not be indicated, depending on the stage of the disease. (15, 714, 16, 17, 2125, 29, 30) Document1 Page 65 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Whether or not the underlying cause(s) can be relieved or treated, all patients will benefit from management of the symptom using education, energy conservation and breath control, airflow and medications. Table 2: Underlying Causes of Dyspnea & Treatment of Choice Underlying Causes Treatment of Choice Airway obstruction Anemia – severe Anxiety Chronic obstructive pulmonary disease (COPD)/Asthma Radiotherapy/steroids/stenting/tracheostomy Transfusion may be indicated Benzodiazepines and Nonpharmacological interventions Conventional inhalers/nebulizers/steroids/anticholinergic. Many smokers live with undiagnosed and untreated COPD, which exacerbates malignancyrelated dyspnea(29) (31), BiPaP Congestive Heart Failure (CHF) Treat with conventional medications(32) /Coronary Artery Disease (CAD) ie). diuretics, ACE inhibitors, vasodilators, opioids Arrhythmias Effusions – pleural, Drain –if clinically significant with respect to the patient’s dyspnea; pericardial, peritoneal pleurodesis or indwelling pleural catheter for recurrent pleural effusion; pericardial window ie). pericentesis Fatigue/deconditioning, weakness Infection: Pneumonia, pericarditis Activity to tolerance, pulmonary rehabilitation exercises may be helpful Lung damage from chemotherapy, radiation or surgery Lymphangitic carcinomatosis Neuromuscular (ALS, CVA, poliomyelitis, myasthenia gravis) Consult oncologist (full dose may not yet have been given), steroids for radiation pneumonitis Pulmonary emboli Pain Primary or metastatic tumour (hepatomegaly, phrenic nerve lesion) Pulmonary fibrosis Superior vena cava (SVC) obstruction Recommendation 3 Antibiotics, antifungal, antiviral if appropriate Corticosteroids, diuretics No specific therapy; apply the Nonpharmacological and pharmacological suggestions outlined below. For Amyotrophic Lateral Sclerosis (ALS) patients – BiPap if appropriate Anticoagulation, filter if appropriate Often exacerbates dyspnea – appropriate analgesia Chemotherapy may be indicated – reduces the incidence of ascites/ pleural effusions in ovarian cancer and ascites in intraabdominal cancer. As above, radiotherapy may relieve airway obstruction Steroids; reassessment of oxygen requirements with disease progression Steroids; consult oncologist for treatment of underlying tumour, radiotherapy Education Dyspnea is a distressing symptom to experience and to witness. Providing information and education is foundational to enhance the patient and family’s ability to cope(2, 46, 8, 10,12, 14, 19, 25, 29) Document1 Page 66 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · Explain to the patient and family what is understood about the multiple triggers of dyspnea (i.e., restriction of respiratory movement, obstructions, and muscle weakness). It is not simply related to oxygenation and therefore many different strategies together can make a difference. Reinforce that this is a symptom that can be managed.(2, 10) Develop a clear plan for the patient and family to address the pattern of shortness of breath and the patient’s way of coping.(2, 3, 10) Teach the purpose of each medication, particularly opioids, as families often do not understand the role of these medications. Ensure an understanding of using regular and breakthrough medications. This is a key to effective management.(3) Known COPD patients often use inhalers incorrectly. Consider the use of nebulisers and spacers. Ensure patient’s compliance.(1) Review Shortness of Breath teaching pamphlet with patient and family (see Appendix B). Recommendation 4 Treatment: Nonpharmacological Energy conservation and breath control · Explain how to incorporate pacing and planning.(1, 2, 4, 12) · Teach relaxation training and breath control.(16, 810, 14, 15, 18, 20, 24) · Encourage activity to tolerance and assist with energy conservation. Refer to Occupational Therapy (OT) – for energy conservation, Physiotherapy (PT) – for breath control, and to NH HPC consult team – for consultation when patient situations are highly complex.(1, 2, 5, 13, 24, 33) Air flow · Open windows and air movement, such as a fan, can be very helpful. Cool air blowing on the face likely triggers reflexes in trigeminal nerve, providing a sense of relief from dyspnea.(17, 914, 16, 18, 19, 25) Environment · Cool and humidify dry air, eliminate irritants in air.(2, 4, 7, 12, 18, 19, 25, 34). Maintain loose sheets over the patients and ensure visitors are not “crowding” the patient.(40) Positioning · Avoid compression of abdomen or chest when positioning.(2, 3, 57, 1013, 19) · Try placing in semiFowlers position (raising head and upper torso). (40) · Patient may direct optimal position for themself Support · Offer psychosocial support and/or counseling.(1, 3, 4, 8, 13, 19, 20) · Alternative therapies for relaxation include: massage, therapeutic touch, visualization, music therapies.(13, 6, 9, 10, 14, 19) · Acupuncture or acupressure.(2, 4, 9, 13, 15, 28) Document1 Page 67 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 5 Treatment: Pharmacological Opioids · Opioids are the drug of first choice in the palliation of dyspnea in advanced disease of any cause. (16, 814, 16, 18, 19, 21, 22, 24, 25, 27, 29, 30, 34, 35) · When dyspnea occurs with most/any activity or for dyspnea at rest, initiate opioids while continuing with Nonpharmacological strategies.(1, 3, 25) · Dose is individualized and titrated until patient states they are comfortable or until restlessness, agitation or apparent breathlessness are controlled in non verbal/confused patients.(14, 8, 12, 19, 22, 27, 30, 36) Continued titration may be necessary as tolerance develops. · Nebulized opioids have NOT been shown to be superior to oral opioids and are therefore not recommended.(14, 6, 1013, 21, 22, 24, 30, 34) · Relief occurs in the absence of significant changes in blood gases or oxygen saturation.(1, 3) · Respiratory depression from opioids is rare(14, 9, 11, 12, 14, 22, 34, 36) and they do not hasten death if appropriately titrated.(1, 3, 4, 9, 12, 13) · Provide access to prophylactic antiemetic and introduce palliative care bowel protocol to avoid iatrogenic symptoms when initiating opioids.(1, 6, 11, 18, 22) · If using parenteral route remember S.C. and I.V. = ½ PO dose (for example 10 mg I.V. or S.C. = 20 mg PO) for morphine and hydromorphone. · Opioid naïve protocol(2, 4, 6, 11, 12) o Morphine 2.5 to 5 mg PO q4h.(13) Use lower dose in the elderly. o Hydromorphone 0.5 to 1 mg PO q4h.(2) Use lower dose in the elderly. o Oxycodone 5mg PO. Titrate dose q4h. o Consider hydromorphone in the elderly and if there is decreased renal function. o Breakthrough ½ of q4h dose (or 10% of TDD) ordered q1h p.r.n.(27) · Opioid tolerant – increase current dose by 25% to 50%.(24, 9, 22, 27) Corticosteroids · Corticosteroids are particularly indicated in the presence of bronchial obstruction, SVC or lymphangitic carcinomatosis. They may also be useful in pulmonary fibrosis for brief periods.(5, 7, 13, 16, 29) Taper and avoid longterm use if possible (increased risk of proximal myopathy which can be very debilitating).(1, 3, 10, 13, 16, 29) · Initiate dexamethasone at 8 to 24 mg PO or S.C. or I.V. daily depending on severity of dyspnea.(2, 3) Doses may be divided b.i.d. Neuroleptics · Neuroleptics can be a useful adjuvant in chronic dyspnea.(4) · Methotrimeprazine: starting dose 2.5 to 5 mg q8h and titrate to effect. Start low to test tolerance as wide variation in patient response; may require much higher doses to 25 mg q4h PO or SC or IV depending on severity of dyspnea.(2) Document1 Page 68 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Benzodiazepines · Try to use on a p.r.n. rather than regular dosing schedule, for severe anxiety and respiratory “panic attacks”.(17, 10, 13, 14, 16, 17, 19, 25, 29, 34) · Lorazepam 0.5 to 2 mg SL q24h p.r.n.(2, 4, 6) Oxygen · There are multiple triggers contributing to the sensation of dyspnea. Hypoxemia is only one. Measure oxygen saturation to determine if hypoxemia is a factor in the patient’s experience of dyspnea. · Careful selection is necessary to identify those people who will benefit from oxygen therapy. Individualized care is paramount.(14, 6, 7, 16, 19, 21, 24, 25, 37) Hypoxic patients: · There is lowgrade scientific evidence that both oxygen and airflow improve dyspnea in hypoxic patients with advanced disease at rest.(26, 9, 11 14, 16, 25, 27, 29, 37) · Provide supplemental oxygen therapy for hypoxic patients according to the Home Oxygen Program guidelines (see Appendix A). Nonhypoxic patients: · A systematic review showed that there is insufficient evidence that supplemental oxygen is beneficial for nonhypoxic patients.(37, 38) · Use other interventions as first line to manage dyspnea with nonhypoxic patients. · The Home Oxygen Program guidelines will not fund supplemental oxygen at home for nonhypoxic patients.(39) · If dyspnea is not managed with maximum treatment and medications, refer for hospice palliative care consultation. Recommendation 6 Diagnosis of acute severe dyspnea during the last hours of life Diagnosis of acute severe dyspnea or respiratory distress occurring during the last hours of life requires crisis intervention: · · · · Treat aggressively with opioids as well as sedatives until comfort is achieved.(2, 4) Opioid naïve – use morphine 5 mg I.V. or S.C. bolus q5 to 10 min. Double dose if no effect every three doses.(2) Opioid tolerant – give full regular PO Q4h dose as S.C. or I.V. q5 to 10 min (for I.V.) or q10 to 15 min (for S.C.) If ineffective double dose as above. Use one of the following with opioid: midazolam 5 mg S.C. or I.V. q5 to 15 min. p.r.n., lorazepam 4 mg I.V. or S.C. q5 to 15 min. p.r.n., methotrimeprazine 25 mg q5 to 15 min. p.r.n., phenobarbital 90 to 120 mg q5 to 15 min. p.r.n. or diazepam 5 to 10 mg I.V. q5 to 15 min. p.r.n. Document1 Page 69 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · Use incremental titration until patient comfortable, determined by subjective as well as objective means.(4) For consultation contact your local Hospice Palliative Care Physician lead, pharmacist lead, or nurse consultant. If unavailable call the palliative care consultation phone line 18777115757. References Information was compiled using the CINAHL, Medline (1996 to March 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using respiratory terms in conjunction with palliative/hospice/end of life/dying. 1. Leach R. Palliative medicine and nonmalignant, endstage respiratory disease. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 895 916. 2. Gallagher R. Dyspnea. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 365 75. 3. Chan KS, Sham M, M. K., Tse DMW, Thorsen AB. Palliative medicine in malignant respiratory diseases. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 587 618. 4. Gallagher R. An approach to dyspnea in advanced cancer. Canadian Family Physician. December 2003;49:1611 6. 5. Cox C. Nonpharmacological treatment of breathlessness. Nursing Standard. January 16, 2002;16(24):33 6. 6. Davis CL. ABC of palliative care: Breathlessness, cough, and other respiratory problems. British Medical Journal. October 1997;315:931 4. 7. Esper P, Heidrich D. Symptom Clusters in Advanced Illness. Seminars in Oncology Nursing. February 2005;21(1):20 8. 8. Kvale PA, Simoff M, Prakash UBS. Palliative care. Chest 2003 Jan; 123(1): Suppl: 284S311S (216 ref). January 2003. 9. Dudgeon D. Managing dyspnea and cough. Hematology Oncology Clinics of North America. 2002;16:557 77. 10. ATS. Dyspnea. Mechanisms, assessment and management: a consensus statement of the American Thoracic Society. American Journal of Respiratory Critical Care Medicine. January 1, 1999;159(1):321 40. 11. Frozena C. Easing Endstage Respiratory Symptoms in Dying Patients. Home Healthcare Nurse.April 1998;16(4): 256 60. 12. Winn PAS, Dentino AN. Quality palliative care in longterm care settings. Journal of the American Medical Directors Association 2004 MayJun; 5(3): 197206. 13. Jacobs LG. Managing respiratory symptoms at the end of life. Clinics in Geriatric Medicine 2003 Feb; 19(1): 225 39. 14. Wheeler MS. Palliative Care is more than Pain Management. Home Healthcare Nurse. April 2004;22(4):250 5. 15. Pan CX, Morrison SR, Ness J, FughBerman A, Leipzig RM. Complementary and Alternative Medicine in the Management of Pain, Dyspnea, and Nausea and Vomiting Near the End of Life: A Systematic review. Journal of Pain and Symptom Management. December 13, 1999;20(5):374 87. 16. Rousseau P. Nonpain symptom management in the dying patient. Hospital Physician 2002 Feb; 38(2): 516. 17. Dudgeon D. Physiological Changes and Clinical Correlations of Dyspnea in Cancer Outpatients. Journal of Pain and Symptom Management. May 5 2001;21(5):373 9. 18. Abernethy AP, Currow DC, Frith P, Fazekas BS, McHugh A, Bui C. Randomised, double blind, placebo controlled crossover trial of sustained release morphine for the management of refractory dyspnoea. British Medical Journal. September 6, 2003;327:523 8. 19. Ross DD, Alexander CS. Management of Common Symptoms in Terminally Ill Patients: Part II Constipation, Delirium and Dyspnea. American Family Physician. September 15, 2001;64(6):1019 26. 20. Bredin M, Corner J, Krishnasamy M, Plant H, Bailey C, A’Hern R. Multicentre randomised controlled trial of nursing intervention for breathlessness in patients with lung cancer. British Medical Journal. April 3, 1999;318:901 5. 21. Dudgeon D. Dyspnoea. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. 22. LeGrand SB, Khawam EA, Walsh D, Rivera NI. What’s new in therapeutics? Opioids, respiratory function, and dyspnea. American Journal of Hospice and Palliative Care 2003 JanFeb;. 1p;20(1):5761. 23. Sorenson HM. Dyspnea assessment. Respiratory Care. November 2000;45(11):1331 41. Document1 Page 70 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 24. ONS. Measuring Oncology Nursing Sensitive Patient Outcomes: EvidenceBased Summary Dyspnea. 2006 [cited May 2006]; Available from: http://www.ons.org/outcomes/Clinical/pdf/DyspneaEvidenceSummary.pdf 25. NCCN. Clinical Practice Guidelines in Oncology Palliative Care. 2005 [cited April 2005]; Version 2:[Available from: http://www.nccn.org/professionals/physician_gls/PDF/palliative.pdf 26. Gift AG, Narsavage G. Validity of the numeric rating scale as a measure of dyspnea. American Journal of Critical Care. May 1998;7(3):200 4. 27. Allard P, Lamontagne C, Bernard P, Tremblay C. How Effective are Supplementary Doses of Opioids for Dyspnea in Terminally Ill Cancer Patients? A Randomized Continuous Sequential Clinical Trial. Journal of Pain and Symptom Management. April 1999;17(4):256 65. 28. Lewith GT, Prescott P, Davis CL. Can a standardized acupuncture technique palliate disabling breathlessness: a singleblind, placebocontrolled crossover study. Chest 2004 May; 125(5): 178390. 29. O’Donnell DE, Aaron S, Bourbeau J, Hernandez P, Marciniuk D, Balter M, et al. Canadian Thoracic Society recommendations for management of chronic obstructive pulmonary disease. Canadian Respiratory Journal. May/ June 2003;10(Supplement A):11A 33A. 30. Jennings AL, Davies AN, Higgins JPT, Broadley K. Opioids for the palliation of breathlessness in terminal illness [Systematic Review]. Cochrane Database of Systematic Reviews. 2006(1). 31. British Columbia Medical Association, Guidelines and Protocols Advisory Committee. Chronic Obstructive Pulmonary Disease (COPD). 2005 [cited July 31st, 2006]; Available from: http://www.healthservices.gov.bc.ca/msp/protoguides/gps/copd.pdf 32. British Columbia Medical Association, Guidelines and Protocols Advisory Committee. Heart Failure Care – Guidelines and Protocols. 2003 [cited July 31, 2006]; Available from: http://www.healthservices.gov.bc.ca/msp/protoguides/gps/ heartfailure.pdf 33. Registered Nurses’ Association of Ontario. Nursing Best Practice Guideline: Nursing Care of Dyspnea: The 6th Vital Sign in Individuals with Chronic Obstructive Pulmonary Disease (COPD). Nursing Best Practice Guidelines Program 2005 [cited 2006 July 31st, 2006]; Available from: http://www.rnao.org/Storage/11/604_BPG_COPD.pdf 34. Manning HL. Dyspnea treatment. Respiratory Care. November 2000;45(11):1342 50. 35. Jennings AL, Davies AN, Higgins JPT, Gibbs JSR, Broadley KE. A systematic review of the use of opioids in the management of dyspnoea. Thorax. March 20, 2002;57(11):939 44. 36. Boyd K. Oral morphine as symptomatic treatment of dyspnoea in patients with advanced cancer. Palliative Medicine. 1997;11:277 81. 37. Booth S, Anderson H, Swannick M, Wade R, Kite S, Johnson M. The use of oxygen in the palliation of breathlessness.A report of the expert working group of the scientific committee of the association of palliative medicine. Respiratory Medicine. August 21, 2003;98:66 77. 38. Gallagher R, Roberts D. A systematic review of oxygen and airflow on relief of dyspnea at rest in patients with advanced disease of any cause. Journal of Pain and Palliative Care Pharmacotherapy. 2004;18(4):3 15. 39. Northern Health Authority. Home and Community Care, Community Respiratory Services, Home Oxygen Program, Guidelines 40. Harrigan Consulting. Best Practices for the Nursing Care of the Older Adult. Network of Excellence for Geriatric Services. Northern Health – Clinical Practice Guidelines – End of Life Care – April 2007. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 71 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix A NH Home Oxygen Program (HOP) Application:(39) http://docushare.northernheatlh.ca/docushare/dsweb/Get/Document13383 Form #530002004 Rev 06/07 The clinical eligibility criteria for the NH Home Oxygen Program (HOP) apply to the palliative patients: · Arterial blood gas on room air showing a PaO2 ≤ 55 mmHg in a steady state reflecting a chronic condition (Chronic Obstructive Pulmonary Disease or Interstitial Lung Disease), OR · Steady state daytime hypoxemia with oxygen saturation sustained continuously for 6 minutes, OR · PaO2 = 56 to 60 mmHg with evidence of cor pulmonale, pulmonary hypertension, or congestive heart failure (with ejection fraction less than 20%) · Exercise limited by hypoxemia and documented to improve with supplemental oxygen (exercise in this instance may mean activities of daily living) · Nocturnal hypoxemia In the case of palliative patients in their last few months of life when an arterial blood gas is an inappropriately invasive procedure, application for the HOP subsidy without an ABG, requires a resting room air oxygen saturation below 88% for 6 minutes. This can be documented in the home by homecare nursing staff. The NH HPC Consult team is very willing to accept referrals for dyspnea assessment and recommendations. Document1 Page 72 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix B Shortness of Breath Shortness of breath, breathlessness, or dyspnea are terms used to describe awareness of difficulty in breathing. Like pain, it is a sensation that can be felt only by the person experiencing it and its causes are many and varied. You may be short of breath only with activity, and be comfortable at rest. Or you may be aware of the effort of breathing even at rest. When this is the case, demands you may not think of as work can make your breathing worse: eating and digesting food after eating; dealing with discomfort such as constipation, pain, or a fever; even laughing. Simply anticipating some event can increase the work of breathing. What can you do to keep your breathing at a comfortable level? · · · · · · · · · · Move slowly and pace your activities within your breathing tolerance. Slight shortness of breath is easier to recover from than extreme shortness of breath from rushing or overexertion. Rest before and after an activity (including eating). Use relaxation techniques in your daily routine such as visualization, self hypnosis, and deep slow breathing. Be aware of the role anxiety may play in your shortness of breath. Getting ready for an activity that will require effort can make you more short of breath in anticipation. To avoid this, think about your breathing and slow it down to a comfortable level before beginning an activity. Take medications prescribed for your shortness of breath before activities that are particularly difficult, e.g., dressing or bathing. Plan ahead about what you can do if you become short of breath. Use fans to move air in your environment. Avoid holding your breath during an activity. When getting out of a chair or bending over to put on your shoes, breathe out as you bend and continue to breathe at your normal pace. Do not hold your breath while climbing the stairs. Be aware of your breathing pattern. When first feeling short of breath, slow down your activity, concentrate on your breathing and slow it down. Slow your breath by breathing in through your nose, and out very gently through lips loosely pursed as if you are going to whistle. Tell family or friends what helps you manage your breathing. For example, turning a fan on; staying with you but staying quiet; putting their hand gently on your shoulder; reminding you to breathe more slowly. Are there medications to help? · Medications such as morphine and hydromorphone are often very effective in decreasing the feeling of shortness of breath. These medications are used in the Document1 Page 73 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · same way as when treating pain. A regular dose is given for constant relief, with “breakthrough” or “rescue” doses for times of when shortness of breath feels worse. People who are short of breath often don’t want to use morphine or hydromorphone medications because of worries about addiction or overdosing. These concerns are common, but these medications are very safe. Addiction is rare and side effects can be easily managed. If you feel a great deal of anxiety due to shortness of breath, antianxiety drugs can be used on a regular or as needed basis. Methotrimeprazine may be useful as a regular antianxiety drug. For acute, sudden episodes of shortness of breath, lorazepam may be helpful. Do you need oxygen? · Not always. Oxygen can help decrease shortness of breath for those people whose lungs cannot move enough oxygen into their bloodstream. But, for many people who are short of breath, the lungs do take in enough oxygen or they may retain too much carbon dioxide. In this case, oxygen may not help. Other strategies such as air blown on the face by fans, medications and other techniques will often be more helpful. What can you do when your shortness of breath gets worse? 1. Reduce your activity. 2. Get supported in a relaxed position. 3. Concentrate on your breathing, gradually slowing the rate and deepening your breaths. In your mind say “slower breath in, longer breath out” until you feel your breathing responding to your message. 4. Try distraction, such as television, music, or having a friend read. 5. If your shortness of breath does not ease to a tolerable level with these strategies, call your physician and discuss adjusting your medication. Shortness of breath can be a lonely, frightening and overwhelming experience. To cope with it, you will likely need to use several of the approaches described above. Shortness of breath is a symptom that can be managed. By working with your doctor, nurse, pharmacist and therapists, your shortness of breath can be eased and you can feel more comfortable. Patient Teaching Handout Northern Health Adapted from Fraser Health Authority / Vancouver Coastal Authority Approved by: NH HPC Consult Team, October 2008 Document1 Page 74 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition EXSANGUINATION Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of exsanguination. This guideline does not address disease specific approaches in the management of bleeding. Although rare, exsanguination does occur in advanced stage palliative care patients.(1) Clinically significant bleeding occurs in 6% to 10% of patients with advanced cancer.(2) 3% of lung cancer patients have terminal massive hemoptysis.(2) Definition of Terms Exsanguination – extensive loss of blood due to internal or external hemorrhage.(3) Standard of Care 1. Assessment 2. Education 3. Treatment: Nonpharmacological 4. Treatment: Pharmacological Recommendation 1 Assessment for the Potential for Exsanguination Identifying the underlying cause of exsanguination is essential in determining the interventions required (see Table 1). Document1 Page 75 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1: Causes of Exsanguination in Palliative Care Patients(1) ENT tumour Carotid artery erosion from neck metastases Oropharyngeal tumour erosion in mouth Gastrointestinal hemorrhage Gastroduodenal ulceration with melena or hematemesis Small or large bowel bleeding with melena (often associated with severe colic) or hematochezia Bladder Hematuria due to tumour, DIC or leukemia Leukemia or blood dyscrasia Possible multiple sites, but external mouth or nasal bleeding is obviously distressing. Extensive bruising is also visually difficult for many family members Disseminated Intravascular Coagulation (DIC) Due to various causes such as sepsis Other Ruptured aortic aneurysm (4) Tumour erosion into adjacent vessels · Massive hemoptysis is rare. It is most apt to occur in primary squamous cell tumours of the lung (not lung metastases) and is usually heralded by one or more episodes of milder hemoptysis.(5) Recommendation 2 · · Education As much as possible prepare family ahead of time or provide explanation when unexpected event occurs. Advanced planning is necessary for all patients with the potential to bleed, as this symptom is a source of considerable distress for patients, family and staff.(1, 2) Recommendation 3 Treatment Nonpharmacological General measures · · Consider stopping medications associated with increased bleeding such as warfarin, heparins, NSAID’s. ASA, clopidogrel, ticlopidine Correct any underlying systemic causes if possible Rapid Blood Loss The patient may be conscious for a short period of time, 20 seconds to several minutes before lapsing into a hypoxic coma followed by a cardiac arrest. It is not painful but often a terrifying experience for the patient and especially for the family and staff.(1) If this scenario is a reasonable possibility, nonpharmacologic preparations are made as follows:(1) Document1 Page 76 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · Have 3 to 4 large towels close to the bedside and cover blood as it occurs to reduce the visual impact (black or dark coloured towels can be used to minimize the sight of blood).(1, 4, 6) Have several face cloths close to bedside to wipe the patient’s mouth and face.(1) Hold the patient’s hand or hug them while providing quieting and comforting words until they drift into a coma and die.(1, 6) If family are not in the room ensure the blood is covered and the patient’s face is clean prior to their arrival.(1) The patient will feel cold because of hypotension and will need warm blankets.(6) This is a traumatic experience for health care providers. Time should be taken to support one another and provide reassurance for actions and feelings.(1) Prolonged Bleeding The bleeding may be visible or invisible, as in a gastrointestinal or other hemorrhage. Bleeding could be rapid (in the case of carotid artery erosion) or over several hours (when smaller vessels are affected).(1) In the latter case, the patient may be conscious for a longer period, although confusion and drowsiness will arise from progressive hypoxia and hypotension. The approach taken is:(1) · · · · · · Towels as above at bedside in case of massive bleeding.(1, 4, 6) Use suction directly at the site of bleeding to remove all or most of the blood. This can be very effective visually and also help prevent coughing or choking in oral hemorrhage.(1) Direct pressure – this will not stop the bleeding. Towels and suction are more practical at this point.(1) Have family or another staff provide physical touch and comfort.(6) Family will need frequent support and reassurance during this phase of dying. They may need to leave the room.(1) The patient will feel cold because of hypotension and will need warm blankets.(1, 6) For patients with hemoptysis maintenance of an adequate airway should occur.(4) This can be accomplished with the Trendelenburg position or positioning patient with the bleeding side (if known) down.(5) Recommendation 4 Treatment: Pharmacological Rapid Blood Loss · Give an I.V. bolus of 5 to 10 mg midazolam (or lorazepam or diazepam) and/or morphine 5 to 20 mg I.V. (dose depends on opioid tolerance). However, there is usually insufficient time for this and it is better spent holding the patient.(1, 5) If the patient is at home and this is anticipated, have the medications predrawn at the bedside. Document1 Page 77 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Prolonged Bleeding · Use I.V. boluses of diazepam or lorazepam OR I.V. or S.C. boluses of morphine OR midazolam S.C. infusion as needed for sedation depending on the patient’s reaction to bleeding and imminent death.(1) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using exsanguination/bleeding terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Gallagher R. Respiratory. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 363 393. 2. Prommer E. Management of bleeding in the terminally ill patient. Hematology June 2005;10(3):16775. 3. Dorland’s Pocket Medical Dictionary. 24 th edition. Exsanguination. W.B. Saunders Company. 1989. p. 225. 4. WredeSeaman LD. Management of Emergent Conditions in Palliative Care. Primary Care: Clinics in Office Practice. June 2001;28(2):317 28. 5. Waller A, Caroline NL. Hemoptysis. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA; 2000. p. 2534. 6. Dean M, Harris JD, Regnard C, Hockley J. Bleeding. Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 6770. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 78 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition FATIGUE Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical setting to which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) that are living with advanced life threatening illness and experiencing the symptom of fatigue. This guideline does not address disease specific approaches in the management of weakness. Fatigue is one of the most common symptoms in advanced cancer and is nearly universal in the terminal stages of illness.(1) Fatigue is reported from 36% to 78% in studies of cancer patients at various stages of their disease.(2) Definition of Terms Fatigue is defined as “a subjective perception and/or experience related to disease, emotional state and/or treatment. Fatigue is a multidimensional symptom involving physical, emotional, social and spiritual wellbeing and affecting quality of life.”(3) The words asthenia and fatigue are often used interchangeably by health professionals.(2, 4, 5) Patients and families often use a number of words interchangeably to describe weakness; drowsiness, tiredness, fatigue, lethargy, reduced alertness.(6) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Assessment of Fatigue Ongoing comprehensive assessment is the foundation of effective management of fatigue, including interview, physical assessment, medication review, medical and surgical review, sleep patterns, psychosocial review, review of physical environment and appropriate diagnostics. Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family(2) (see Table 1). Document1 Page 79 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1: Fatigue Assessment using Acronym O, P, Q, R, S, T, U and V * O P When did it begin? How long does it last? How often does it occur? Onset Provoking / What brings it on? What makes it better? What makes it worse? Palliating Q R Quality Region / What does it feel like? How are you sleeping? How is your appetite? Have you lost weight? Is this an overall feeling or is it localized? Radiation S T U Severity Treatment What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? Understanding/ How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Document1 Page 80 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Physical Examination(2,7,8) REGION LOOK FOR SUGGESTS Head Mouth Abdomen Extremities Coarse hair Thinning of lateral third of eyebrows Lid lag Miosis Conjunctival pallor Cheliosis, reddened shiny tongue Palpable bladder Asterixis Back Neurologic Tenderness to percussion over vertebrae Proximal myopathy Hypothyroid Hypothyroid Hypothyroid Opioid overdose Anemia Vitamin deficiencies Spinal cord compression Hepatic or renal insufficiency Hypokalemia Spinal cord compression EatonLambert, steroid myopathy, or other myopathic syndrome EatonLambert paraneoplastic syndrome Eyes Absent deep tendon reflexes (DTRs) that reappear after 10 seconds of maximal voluntary contraction Prolonged relaxation time of DTRs Hyperactive DTRs Spasticity, sensory loss, extensor plantar Hypothyroid Acute cord compression Acute cord compression Laboratory studies Hemoglobin, WBC count, serum sodium, potassium, calcium, albumin, magnesium, blood glucose, serum urea, creatinine, liver enzymes, TSH, triiodothyronine, thyroxine, applicable drug levels (phenytoin, digoxin).(1) Recommendation 2 Diagnosis Identifying the underlying cause of weakness is helpful in determining the interventions required. Use an objective scale, such as the Palliative Performance Scale (PPS) (see Appendix A) or the performance status scale of the Eastern Cooperative Oncology Group (ECOG)(2) (see Appendix B). The diagnosis of fatigue is based on the patient’s report of the symptom.(5) It is important to document therapeutic outcome in both subjective and objective perspectives in palliative care of cancer patients.(9) Causes of Fatigue: · Fatigue usually has multiple causes.(1, 2, 5, 8, 1012) · Tumour related: o Altered metabolism.(2) o Cancer cachexia – wasting affects both skeletal and cardiac muscle.(2, 46, 11) o o o Document1 Cancerinduced cytokines and other substances.(2, 4) Paraneoplastic syndromes – EatonLambert and other myopathies.(2, 4, 6, 7) Spinal cord compression.(2, 6) Page 81 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition o Tumour burden.(2, 6) · Treatment related: o Chemotherapy.(4, 68, 12) o Radiation therapy.(4, 68, 12) o Surgery.(4) o Biotherapy.(12) · Non cancer related: o Autonomic failure – postural hypotension, occasional syncope, fixed heart rate and gastrointestinal symptoms (nausea, anorexia, constipation or diarrhea).(7, 11, 13) o Cardiopulmonary disorders.(1, 2, 4, 5, 79, 12) · Reversible causes: o Anemia.(2, 4, 11, 12) o Bed rest.(1, 2, 4, 6, 7, 11, 12) o Bleeding. o Depression(47, 12, 13) or anxiety.(4, 5, 12) o Dehydration.(2, 4, 6, 7, 13) o Drugs – opioids, antidepressants, phenothiazines(2, 47, 12, 13) beta blockers(12) phenytoin, levothyroxine. o Endocrine imbalances – hypothyroid, hypoadrenalism (most often due to rapid withdrawal of corticosteroid medication),(8, 12) diabetes mellitus(4) and Addison’s disease.(46) o Hypercapnia or hypoxia.(1, 2, 47, 13) o Insufficient sleep.(1, 2, 48, 12, 13) o Metabolic disturbances – hypercalcemia, hypokalemia(4) and hyponatremia.(1, 2, 48) o Occult or chronic sepsis.(57) o Poor nutrition.(1, 5, 8, 12, 13) o Unrelieved symptoms – pain, diarrhea, nausea and vomiting.(2) Recommendation 3 · · · Education Patients and family will focus on the symptom rather than its underlying cause. Often this complaint is viewed as the patient has “given up” or is “not fighting”. Education must center on what is and is not correctable or beyond the patient’s control(14) and giving the patient “permission to rest”.(13) Work with patients and family caregivers to improve assessment of fatigue and identify management strategies.(2, 4, 6, 8, 13, 15) Help patient plan periods of rest and periods of activity to maximize the energy the patient has available for things that are really important to him/her.(2, 46, 8, 12, 15) Help the patient to delegate tasks that he/she is no longer able to perform and arrange for assistance where necessary.(2) Document1 Page 82 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · When fatigue is mild, encourage moderate physical activity to preserve muscle function. As weakness progresses, use physical aids (walkers, grab bars) to help preserve mobility.(16) Rehabilitation goals need to be carefully weighed when the patient has a short life expectancy to assure that the benefits of treatment outweigh the burdens.(2, 4, 5) Recommendation 4 Treatment: Nonpharmacological Anemia – refrain from transfusion unless the patient is severely symptomatic and the patient is capable of benefiting from an increased red cell mass (ECOG of 3 or better).(9) Depression/anxiety disorders – counseling.(12, 16) Patient mobility may help combat depression.(1) Massage and aromatherapy have been found to offer some relief for depression related fatigue.(13) Consider attention restoring activities (exposure to natural environment, music).(12, 14) Dehydration – give fluids orally(4) or parenterally (I.V. or hypodermoclysis).(2) Hypercalcemia – give hydration.(2, 6) Hypokalemia – for severe hypokalemia (potassium less than 2.8 mEq per litre) give potassium rich foods (citrus juice, tomatoes, bananas).(4) Hyponatremia – fluid restriction is frequently undesirable for patients and onerous for caregivers.(7, 13) Poor nutrition – nutritional counseling(6, 12) although in late stages eating becomes more important for pleasure and comfort than nutrition.(2, 4, 8, 15) Prolonged immobilization – physiotherapy.(7, 12) Exercise has been shown to have the strongest evidence of benefit.(11) Daily stretching or isometric muscle contractions can help maintain muscle strength.(5, 7, 14) Sleep disturbances – sleep therapy(12, 13) such as stimulus control (avoiding caffeine and stimulants, going to bed when sleepy), sleep consolidation strategies (avoiding long naps, limiting time in bed) strategies to reduce cognitiveemotional arousal and cognitivebehavioural interventions (relaxation training).(2) Recommendation 5 Treatment: Pharmacological Anorexia/cachexia – give dexamethasone 4 mg PO daily and multivitamins.(2, 5, 7, 14) Depression – consider psychostimulants. See Northern Health Hospice Palliative Care Symptom Guideline for Depression. Endocrine imbalance – give replacement therapy (thyroid hormone or restart corticosteroids if recently withdrawn).(2) Hypercalcemia – see Northern Health Hospice Palliative Care Symptom Guideline for Hypercalcemia. Document1 Page 83 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Hypokalemia – change loop diuretic to potassium sparing diuretic (spironolactone 100 mg daily) for a few days and recheck serum potassium. Correct hypokalemia with potassium supplement.(2) Insomnia – give sedative or hypnotic medication.(2) Sepsis – give antibiotics and antipyretics where appropriate.(2) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using fatigue/weakness/asthenia terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Lane I. Managing clancerrelated fatigue in palliative care. Nursing Times. 2005 May 3;101(18):3841. 2. Waller A, Caroline NL. Weakness. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA: Butterworth Heinemann; 2000. p. 7784. 3. Ferrell BR, Grant M, Dean GE, Funk B, Ly J. Bone tired: The experience of fatigue and impact on quality of life. Oncology Nursing Forum. 1996;23(10):153947. 4. Sweeny C, Neuenschwander H, Bruera E. Fatigue and asthenia. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 5608. 5. Tyler LS, Lipman AG. Fatigue in Palliative Care Patients. Evidenced Based symptom Control in Palliative Care: Systematic Reviews and Validated Clinical Practice Guidelines for 15 Common Problems in Patients with Life Limiting Disease. 2000;8(1):12941. 6. Dean M, Harris JD, Regnard C, Hockley J. Fatigue, drowsiness, lethargy and weakness. Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 1018. 7. Walker P, Bruera E. Fatigue. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. p. 8995. 8. Sherman DW, Matzo ML, Coyne P, Ferrell BR, Penn BK. Teaching symptom management in endoflife care: the didactic content and teaching strategies based on the endoflife nursing education curriculum. Journal for Nurses in Staff Development JNSD. 2004 MayJune;20(3):10315; quiz 167. 9. Lindholm E, et al. Effects of Recombinant Erythropoietin in Palliative Treatment of Unselected Cancer Patients. Clinical Cancer Research. 2004 October 15;10:685564. 10. Kaasa S, Loge JH. Quality of life in palliative medicine principles and practice. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 196210. 11. Guo Y, Shin KY. Rehabilitation Needs of Cancer Patients. Critical Reviews in Physical and Rehabilitation Medicine. 2005;17(2):8399. 12. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology Cancer Related Fatigue. April 27, 2006; Version 1: Available from: http://www.nccn.org/professionals/physician_gls/PDF/fatigue.pdf 13. Oncology Nursing Society. Fatigue Detailed PEP (Putting Evidence into Practice) Card. December 2005; Available from: http://www.ons.org/outcomes/resources/fatigue.sht mL 14. Paolini CA. Symptoms Management at the End of Life. The Journal of the American Osteopathic Association. October 2001;101(10):609 15. 15. Straatman L. Cardovascular. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 396417. 16. Nausbaum N. Rehabilitation and the Older Cancer Patient. The American Journal of the Medical Sciences. 2004 February;327(2):8690. 17. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and Response Criteria of the Eastern CoOperative Oncology Group. American Journal of Clinical Oncology. 1982;5:64955. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 84 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix A PPS Palliative Performance Scale (PPSv2) version 2 Palliative Performance Scale (PPSv2) version 2 PPS Level 100% Ambulation 90% Full 80% Full 70% Reduced 60% Reduced 50% Mainly Sit/Lie 40% Mainly in Bed 30% Totally Bed Bound Totally Bed Bound Totally Bed Bound Death 20% 10% 0% Full Activity & Evidence of Disease Normal activity & work No evidence of disease Normal activity & work Some evidence of disease Normal activity with Effort Some evidence of disease Unable Normal Job/Work Significant disease Unable hobby/house work Significant disease Unable to do any work Extensive disease Unable to do most activity Extensive disease Unable to do any activity Extensive disease Unable to do any activity Extensive disease Unable to do any activity Extensive disease SelfCare Intake Full Normal Conscious Level Full Full Normal Full Full Normal or reduced Full Normal or reduced Occasional assistance Normal or necessary reduced Considerable assistance Normal or required reduced Mainly assistance Normal or reduced Total Care Normal or reduced Total Care Minimal to sips Total Care Mouth care only Full Full Full or Confusion Full or Confusion Full or Drowsy +/ Confusion Full or Drowsy +/ Confusion Full or Drowsy +/ Confusion Drowsy or Coma +/ Confusion Instructions for Use of PPS (see also definition of terms) 1. PPS scores are determined by reading horizontally at each level to find a ‘best fit’ for the patient which is then assigned as the PPS% score. 2. Begin at the left column and read downwards until the appropriate ambulation level is reached, then read across to the next column and downwards again until the activity/evidence of disease is located. These steps are repeated until all five columns are covered before assigning the actual PPS for that patient. In this way, ‘leftward’ columns (columns to the left of any specific column) are ‘stronger’ determinants and generally take precedence over others. Copyright © 2001 Victoria Hospice Society Document1 Page 85 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Example 1: A patient who spends the majority of the day sitting or lying down due to fatigue from advanced disease and requires considerable assistance to walk even for short distances but who is otherwise fully conscious level with good intake would be scored at PPS 50%. Example 2: A patient who has become paralyzed and quadriplegic requiring total care would be PPS 30%. Although this patient may be placed in a wheelchair (and perhaps seem initially to be at 50%), the score is 30% because he or she would be otherwise totally bed bound due to the disease or complication if it were not for caregivers providing total care including lift/transfer. The patient may have normal intake and full conscious level. Example 3: However, if the patient in example 2 was paraplegic and bed bound but still able to do some selfcare such as feed themselves, then the PPS would be higher at 40 or 50% since he or she is not ‘total care.’ 3. PPS scores are in 10% increments only. Sometimes, there are several columns easily placed at one level but one or two which seem better at a higher or lower level. One then needs to make a ‘best fit’ decision. Choosing a ‘halffit’ value of PPS 45%, for example, is not correct. The combination of clinical judgment and ‘leftward precedence’ is used to determine whether 40% or 50% is the more accurate score for that patient. 4. PPS may be used for several purposes. First, it is an excellent communication tool for quickly describing a patient’s current functional level. Second, it may have value in criteria for workload assessment or other measurements and comparisons. Finally, it appears to have prognostic value. Definition of Terms for PPS As noted below, some of the terms have similar meanings with the differences being more readily apparent as one reads horizontally across each row to find an overall ‘best fit’ using all five columns. 1. Ambulation The items ‘mainly sit/lie,’ ‘mainly in bed,’ and ‘totally bed bound’ are clearly similar. The subtle differences are related to items in the selfcare column. For example, ‘totally bed ‘bound’ at PPS 30% is due to either profound weakness or paralysis such that the patient not only can’t get out of bed but is also unable to do any selfcare. The difference between ‘sit/lie’ and ‘bed’ is proportionate to the amount of time the patient is able to sit up vs need to lie down. ‘Reduced ambulation’ is located at the PPS 70% and PPS 60% level. By using the adjacent column, the reduction of ambulation is tied to inability to carry out their normal job, work occupation or some hobbies or housework activities. The person is still able to walk and transfer on their own but at PPS 60% needs occasional assistance. 2. Activity & Extent of disease ‘Some,’ ‘significant,’ and ‘extensive’ disease refer to physical and investigative evidence which shows degrees of progression. For example in breast cancer, a local recurrence would imply ‘some’ disease, one or two metastases in the lung or bone would imply ‘significant’ disease, whereas multiple metastases in lung, bone, liver, brain, hypercalcemia or other major complications would be ‘extensive’ disease. The extent may also refer to progression of disease despite active treatments. Using PPS in AIDS, ‘some’ may mean the shift from HIV to AIDS, ‘significant’ implies progression in physical decline, new or difficult symptoms and laboratory findings with low counts. ‘Extensive’ refers to one or more serious complications with or without continuation of active antiretrovirals, antibiotics, etc. Copyright © 2001 Victoria Hospice Society Document1 Page 86 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition The above extent of disease is also judged in context with the ability to maintain one’s work and hobbies or activities. Decline in activity may mean the person still plays golf but reduces from playing 18 holes to 9 holes, or just a par 3, or to backyard putting. People who enjoy walking will gradually reduce the distance covered, although they may continue trying, sometimes even close to death (eg. trying to walk the halls). 3. SelfCare ‘Occasional assistance’ means that most of the time patients are able to transfer out of bed, walk, wash, toilet and eat by their own means, but that on occasion (perhaps once daily or a few times weekly) they require minor assistance. ‘Considerable assistance’ means that regularly every day the patient needs help, usually by one person, to do some of the activities noted above. For example, the person needs help to get to the bathroom but is then able to brush his or her teeth or wash at least hands and face. Food will often need to be cut into edible sizes but the patient is then able to eat of his or her own accord. ‘Mainly assistance’ is a further extension of ‘considerable.’ Using the above example, the patient now needs help getting up but also needs assistance washing his face and shaving, but can usually eat with minimal or no help. This may fluctuate according to fatigue during the day. ‘Total care’ means that the patient is completely unable to eat without help, toilet or do any selfcare. Depending on the clinical situation, the patient may or may not be able to chew and swallow food once prepared and fed to him or her. 4. Intake Changes in intake are quite obvious with ‘normal intake’ referring to the person’s usual eating habits while healthy. ‘Reduced’ means any reduction from that and is highly variable according to the unique individual circumstances. ‘Minimal’ refers to very small amounts, usually pureed or liquid, which are well below nutritional sustenance. 5. Conscious Level ‘Full consciousness’ implies full alertness and orientation with good cognitive abilities in various domains of thinking, memory, etc. ‘Confusion’ is used to denote presence of either delirium or dementia and is a reduced level of consciousness. It may be mild, moderate or severe with multiple possible etiologies. ‘Drowsiness’ implies either fatigue, drug side effects, delirium or closeness to death and is sometimes included in the term stupor. ‘Coma’ in this context is the absence of response to verbal or physical stimuli; some reflexes may or may not remain. The depth of coma may fluctuate throughout a 24 hour period. © Copyright Notice. The Palliative Performance Scale version 2 (PPSv2) tool is copyright to Victoria Hospice Society and replaces the first PPS published in 1996 [J Pall Care 9(4): 2632]. It cannot be altered or used in any way other than as intended and described here. Programs may use PPSv2 with appropriate recognition. Available in electronic Word format by email request to [email protected] Correspondence should be sent to Medical Director, Victoria Hospice Society, 1952 Bay Street, Victoria, BC, V8R 1J8, Canada Document1 Page 87 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix B ECOG Performance Status*(17) Grade ECOG 0 Fully active, able to carry on all predisease performance without restriction. 1 Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, e.g., light house work, office work. 2 Ambulatory and capable of all self care but unable to carry out any work activities. Up and about more than 50% of waking hours. 3 Capable of only limited self care, confined to bed or chair more than 50% of waking hours. 4 Completely disabled. Cannot carry on any self care. Totally confined to bed or chair. 5 Dead. The Eastern Cooperative Oncology Group, Robert Comis M.D., Group Chair. Document1 Page 88 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition HICCUPS ***This section is currently under development*** • Protracted attacks are exhausting and distressing, and warrant intervention Causes Persistent hiccups occur in association with a wide variety of diseases, frequently where two or more comorbid conditions coexist. · Diaphragmatic irritation by malignant infiltration, inflammation or infection e.g. chemical pleurodesis, empyema, subphrenic abscess, subphrenic pressure due to hepatomegaly or ascites. · Gastric distention due to outlet obstruction, gastric tumour. · Esophagitis, esophageal obstruction. · Phrenic nerve irritation, e.g. by a mediastinal tumour. · Intracranial disease, e.g. intracranial tumour, brain stem lesion · Uremia Investigation · When the cause is unknown, and depending on clinical situation, a CXR and serum creatinine may be helpful. Nonpharmacological Treatment · simple measures to abort an attack are based on pharyngeal and vagal stimulation, elevation of P CO2 or relief of gastric distention. o pharyngeal stimulation can be achieved by: § eating 12 teaspoons of granular sugar or roughly crushed ice § rolling a swab tip over the midline of the soft palate for one minute. § passage of a suction tube or Foley catheter into the nasopharynx (812 cm to the level of C2, where the catheter is rolled to and fro to stimulate the pharyngeal wall. A foley catheter can be lightly inflated and left in place for a more prolonged stimulatory effect) o massage of the external auditory canal. Document1 Page 89 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition o rebreathing into a brown paper bag or breath holding. o passage of a nasogastric tube to relieve gastric distension. Pharmacological Treatment · many drugs have been suggested – little evidence of efficacy ® o chlorpromazine 1025mg PO/IV/IM q6h or haloperidol (Haldol ) 15mg PO/SC q412h while titrating o baclofen 510mg PO tid o metoclopramide 10 mg q4h PO/SC o anticonvulsants § gabapentin 300 mg PO TID § carbamazepine 100200mg PO bid o for persistent intractable hiccups, baclofen (as above), or midazolam 2.5 mg SC q26h prn or 1060 mg/24h The above information provided from the first edition of the NH Palliative Care Guidelines and Protocols, December 2004. Document1 Page 90 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition HYPERCALCEMIA IN MALIGNANT DISEASE (PALLIATIVE MANAGEMENT) Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of hypercalcemia. This guideline does not address disease specific approaches in the management of hypercalcemia. Hypercalcemia is the most frequent metabolic emergency in oncology and occurs in 10% to 40% of cancer patients.(13) Hypercalcemia most commonly occurs in patients with advanced cancer and is an indicator of poor prognosis.(1, 2, 46) Definition of Terms Hypercalcemia is defined as serum calcium (corrected) greater than 2.6 mmol/L.(3) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Hypercalcemia Assessment Ongoing comprehensive assessment is the foundation of effective management of hypercalcemia, including interview, physical assessment, medication review, medical and surgical review, psychosocial review, review of physical environment and appropriate diagnostics. Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family. Document1 Page 91 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1: Hypercalcemia Assessment using Acronym O, P, Q, R, S, T, U and V * O P When did it begin? How often does it occur? Onset Provoking / What brings it on? What makes it better? What makes it worse? Palliating Q R What does it feel like? Can you describe it? Quality Region / Radiation S T U Severity Treatment What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right Now? At Best? At Worst? On Average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? Nausea/vomiting, constipation, weakness, loss of appetite, confusion or agitation? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? Understanding/ How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Signs And Symptoms: The severity of symptoms are not always related to the degree of hypercalcemia but often reflect the rapidity of onset.(4) Patients do not always exhibit all of the clinical features. The onset of hypercalcemia may be insidious.(3) · · Neurological: fatigue, lethargy, confusion, myopathy, hyporeflexia, seizures, psychosis and coma.(7) The most frequent effect of hypercalcemia is delirium.(8) General: dehydration, polydipsia, polyuria, pruritis.(7, 9) Weakness and bone pain may also be present.(8) Document1 Page 92 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · GI: anorexia, nausea and vomiting, weight loss, constipation, ileus and abdominal pain.(79) Cardiac: shortened QT interval, prolonged PR interval, wide T waves, ventricular and atrial arrhythmias and bradycardia.(7, 9) Arrhythmias, such as bradycardia, can be fatal.(8) Renal: polyuria, polydipsia, dehydration and development of kidney stones.(8) Early: polyuria, nocturia, polydipsia, dehydration, anorexia, easy fatigability, weakness, hyporeflexia, pain may be precipitated or exacerbated by hypercalcemia.(4) Late: apathy, irritability, depression, decreased ability to concentrate, obtundation, coma, profound muscle weakness, nausea and vomiting, constipation, increased gastric acid secretion, acute pancreatitis, pruritus, visual disturbances, sudden death from cardiac dysrhythmias may occur if calcium rises fast, especially in patients taking digoxin.(4) Laboratory Studies: Always relate serum calcium levels to serum albumin levels Method for Calculating Correction of Calcium Level to Reflect Albumin Level: · If serum albumin is less than 40 grams per litre, increase measured calcium by 0.20 mmol per litre for every 10 grams of albumin below 40 grams per litre. · If serum albumin is greater than 40 grams per litre, reduce measured calcium by 0.20 mmol per litre for every 10 grams of albumin over 40 grams per litre. Alternatively: · Corrected calcium (mmol/L) = Measured calcium (mmol/L) + [0.02 x (40 – measured albumin g/L)]. (1, 3, 8) Other possible abnormal results: · Alkaline phosphatase – usually elevated, except in myeloma.(4) · Chloride may be elevated in primary hyperparathyroidism.(4, 5) · BUN, creatinine may be elevated from renal damage.(4) · Electrocardiogram – prolonged PR interval, widened QRS complex, shortened QT, widened T wave, bradycardia.(4) Recommendation 2 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. The most significant intervention in the management of hypercalcemia is identifying underlying cause(s) and treating as appropriate. While underlying cause(s) may be evident, treatment may not be indicated, depending on the stage of disease. Whether or not the underlying cause(s) can be relieved or treated, all patients will benefit from management of the symptom using education, hydration and medications. Document1 Page 93 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Identifying the underlying etiology of hypercalcemia is essential in determining the interventions required. Causes: · · · · · The majority of cases of humoral hypercalcemia of malignancy are associated with impaired gut absorption of calcium and low levels of vitamin D.(9) Secretion of parathyroid hormonerelated protein by the tumour.(6, 8, 10) This occurs in 80% of hypercalcemia cases.(8) Osteolytic skeletal metastases.(4, 8) The extent of metastases does not correlate well with level of calcium.(4) Decreased renal clearance of calcium.(9) Increased gastrointestinal absorption of calcium in response to elevated levels of 1,25dihydroxycholecalciferol (1,25 (OH)2D3, calcitriol) resulting from ectopic production of this vitamin by haematological neoplasms – this occurs rarely.(9) Tumours most often associated with hypercalcemia: · · · · · · · Multiple myeloma – 40% to 50%.(4, 5) Breast – greater than 20% of cases with cancerrelated hypercalcemia.(4, 5) Lung – 20%, usually squamous cell, sometimes adenocarcinoma, rarely small cell.(4) Hypernephroma.(4) Squamous cell cancers of the head and neck and esophagus.(4) Thyroid.(4) Rarely or never – prostate or colorectal cancer.(4) Recommendation 3 Education Teach patients at risk and their caregivers the signs and symptoms of hypercalcemia to promote early recognition of acute rises in serum calcium.(4) Recommendation 4 Treatment: Nonpharmacological Rehydration · Hydration alone may be sufficient for asymptomatic patients with borderline serum calcium.(4) · Adequate hydration reduces serum calcium by a median of 0.25 mmol per litre.(3) · All hypercalcemic patients are dehydrated due to polyuria and vomiting.(4) · Hydration is appropriate for treatable hypercalcemia.(11) Rehydration with 2 to 3 litres per day is now the accepted practice with daily serum electrolyte measurement to prevent hypokalemia and hyponatremia for cases of severe or symptomatic hypercalcemia.(4, 9) · Increase patient’s oral fluid intake to 2 to 3 litres per day, as tolerated.(4) Document1 Page 94 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · Most patients are usually 4 litres behind in their overall fluid balance when a diagnosis of hypercalcemia is made. Rehydration with normal saline should commence at 100 to 120 mL per hour I.V. or by hypodermoclysis based on patient’s cardiac status (e.g., a slower rate should be used in patients prone to CHF). Mobilization: · Mobilization of the patient is important, in that it slows down the loss of skeletal calcium associated with immobility.(4) Diet: · Low calcium diet is needed to control hypercalcemia caused by elevated 1,25 (OH)2D3 but they are unpalatable, impractical and exacerbate malnutrition and have no place in palliative therapy.(3, 4, 9) Recommendation 5 Treatment: Pharmacological Bisphosphonates: · · · · · · · · Bisphosphonates are appropriate to administer when serum calcium (corrected) is greater than or equal to 3 mmol per litre or when serum calcium (corrected) is less than 3 mmol per litre when accompanied by symptoms.(3) Bisphosphonates cause a fall in calcium in 48 hours.(9) These agents are very useful and well tolerated but are quite expensive.(1) Oral bisphosphonates (like clodronate or alendronate) can be used, but in many palliative care patients are not well tolerated. Parenteral drugs including pamidronate and zoledronic acid have been used with success(8) and are better tolerated and more effective than oral.(5) Do not give bisphosphonates until the patient is fully rehydrated and has an adequate urine output.(4) Recheck serum calcium, electrolytes, urea, and creatinine on the 3rd day after administering bisphosphonates.(1) Renal failure is the most serious adverse effect.(3) Bisphosphonates are contraindicated in patients with serum creatinine greater than 400 umol per litre or calculated creatinine clearance of less than 10 mL per minute.(3) In patients with preexisting renal disease and a serum creatinine less than 265 umol per litre, no change in dosage, infusion time or interval of pamidronate is required for multiple myeloma patients.(12) Caution is required in patients receiving other drugs that may affect renal function (NSAIDS, ACE inhibitors, aminoglycosides).(3) o Pamidronate 30 to 90 mg I.V. for severely elevated calcium (over 3.5 mmol per Litre) use 90 mg I.V. bolus in 250 mL(13, 14) to 500 mL NS(4, 10) over 60(13, 14) to 90 minutes.(2, 9) Document1 Page 95 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · Pamidronate has been shown to be superior to clodronate in terms of duration of normal calcium levels achieved.(2, 9) Best given with acetaminophen, 500 mg PO or rectally to prevent pamidronate fever.(4) Usual expected duration of effect of pamidronate is 3 to 4 weeks.(1,3) o Clodronate 1500 mg I.V. over 4 hours in 250 or 500 mL NS(1, 3, 10) or 500 mg I.V. daily for 3 days – dilute in 500 cc NS. · Usual expected duration of action of clodronate is 2 weeks.(1, 3) · Dose adjustment for decreased renal function: if creatinine clearance is 10 to 50 mL per minute a dose reduction of 25% to 50% is recommended.(3) o Zoledronic acid 4 mg in 100 mL NS over 15 minutes I.V.(1, 2, 9, 12) Zoledronic acid has been shown to achieve normal serum calcium levels in more patients, faster and with longer duration than Pamidronate.(9) · Usual expected duration of effect of zoledronic acid is 4 to 6 weeks.(1) · Useful for refractory hypercalcemia treatment.(1) · Fever is a common side effect of zoledronic acid, with renal impairment seen rarely.(5) · Zoledronic acid has been found to be effective in reducing and delaying bone complications across a broad range of solid tumours and multiple myeloma.(2) · Dose adjustment for decreased renal function:(3) Baseline Creatinine Clearance ( mL/min) Greater than 60 50 to 59 40 to 49 30 to 39 Zoledronic Acid Recommended Dose 4 mg 3.5 mg 3.3 mg 3 mg Calcitonin: · · · Calcitonin 4 to 8 international units per kg given S.C. or I.M. q12h (can titrate up to q6h).(3, 4, 16) Calcitonin has a rapid onset of action – approximately 4 hours(9) but has a shorter duration of action(4) and is very useful when a rapid lowering of serum calcium is required(1, 35, 16) but needs to be combined with bisphosphonates.(3, 5, 16) Possible side effects: flushing, mild nausea, crampy abdominal pain.(4) A small risk of hypersensitivity exists due to salmon derivation.(3) Steroids: · Corticosteroids may lower serum calcium if they have an antineoplastic effect on the underlying malignancy.(3) They should be reserved for situations in which bisphosphonates are not easily accessible or are ineffective or in which other indication for corticosteroids (pain or nausea) exist.(3) Document1 Page 96 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · Prednisone 40 to 100 mg daily(9) for up to one week.(4) Hydrocortisone 100 mg I.V. q6h.(7) Dexamethasone 4 mg S.C. q6h for 3 to 5 days. Steroids are particularly useful for hypercalcemia seen with lymphomas and multiple myeloma.(5) Drugs promoting hypercalcemia (thiazide diuretics, lithium, ranitidine, cimetidine, vitamins A and D and preparations containing calcium) should be withdrawn.(4, 9, 15) The routine use of furosemide in conjunction with hydration to promote calcium excretion is not recommended, because of the risk of volume and electrolyte depletion.(3) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane, DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using hypercalcemia terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. de Kock I. Nausea and vomiting. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. 2. Heatley S. Metastatic bone disease and tumourinduced hypercalcaemia: Treatment options. International Journal of Palliative Nursing. 2004;10(1):416. 3. Capital Health Regional Palliative Care Program. Hypercalcemia of Malignancy. March 17, 2005. Available from: http://www.palliative.org/PC/ClinicalInfo/Clinical%20Practice%20Guidelines/PDF%20files/ 3A5%20Hypercalcemia%20of%20Malignancy.pdf 4. Waller A, Caroline NL. Hypercalcemia. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA: Butterworth Heinemann; 2000. p. 36772. 5. Dean M, Harris JD, Regnard C, Hockley J. Emergencies. Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 20119. 6. Iwase M, Takemi T, Manabe M, Nagumo M. Hypercalcemic complication in patients with oral squamous cell carcinoma. International Journal of Maxillofacial Surgery. 2003;32:17480. 7. WredeSeaman LD. Management of Emergent Conditions in Palliative Care. Primary Care: Clinics in Office Practice. June 2001;28(2):317 28. 8. Sakaluk T. Orthopedic. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 41932. 9. Bower M, Cox S. Endocrine and metabolic complications of advanced cancer. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 687702. 10. Elomaa I. Use of Bisphosphonates in Skeletal Metastasis. Acta Oncologica. 2000;39(4):44554. 11. Syme A, Fimrite A. Gastrointestinal. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 301 6. 12. Berenson JR, et al. American Society of Clinical Oncology Clinical Practice Guidelines: The Role of Bisphosponates in Multiple Myeloma. Journal of Clinical Oncology. 2002 September 1;20(17):371936. 13. Surrey Memorial Hospital. Pamidronate Disodium Monograph. In: Surrey Memorial Pharmacy, editor.; 2001. 14. British Columbia Cancer Agency. Pamidronate monograph. In: British Columbia Cancer Agency Pharmacy, editor.; 2005. 15. Lamy O, JenzerClosuit A, Burckhardt P. Hypercalcaemia of malignancy: An undiagnosed and undertreated disease. Journal of Internal Medicine. 2001;250:739. 16. Murphy, K., Nakashima, L., Khoo, K. BCCA Protocol Summary Guidelines for the Diagnosis and management of Malignancy Related Hypercalcemia. June 1999. Revised Jan 2006. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 97 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition LYMPHOEDEMA ***This section is currently under development*** Causes · Interruption of the lymphatic system by surgery, radiation or tumour infiltration. · In cancer patients the incidence is increased if both modalities of treatment are used and obstruction is further increased by recurrent episodes of cellulitis. Clinical Features · Nonpitting edema of the subcutaneous tissues that does not resolve with elevation or rest and is associated with chronic inflammation and fibrosis of the edematous tissues. · Can develop months or years following surgery or radiotherapy to the axillary or inguinal nodes. · When caused by recurrent tumour, palpable disease may be detectable in the groin, axilla or skin. · Treatment will depend on the stage of disease and prognosis. Prevention & Treatment · Strict avoidance of use of tourniquets for venipuncture or BP measurement, and injections in the affected arm. · Protection of the overlying skin with sunscreen, insect repellant and clothing. · Prompt treatment of cellulitis with antibiotics that may need to be continued for several weeks. · Use of support garments, massage, physiotherapy and compression pumps may be of assistance in restoring function and controlling edema. The above information provided from the first edition of the NH Palliative Care Guidelines and Protocols, December 2004. Document1 Page 98 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition MALIGNANT BOWEL OBSTRUCTION Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of bowel obstruction. This guideline does not address disease specific approaches in the management of bowel obstruction. Obstruction occurs in 3% to 42% of malignancies, with the higher number in patients with ovarian cancer.(16) Most commonly seen with colorectal cancer and ovarian cancer (7, 8) but may occur with any cancer having an abdominal or pelvic presence, usually occurring in advanced stages of the disease.(1, 3, 912) Obstructions may be partial or complete, acute or insidious and reversible or irreversible.(1) Obstruction usually leads to local inflammation with luminal accumulation of intestinal fluids, gases and solids producing symptoms and creating a vicious cycle of distension and secretion.(1, 5, 11) The small bowel is more commonly involved than the large bowel (61% versus 33%).(13) Definition of Terms Bowel obstruction occurs when there is blockage of the forward flow of gastric and intestinal contents through the gastrointestinal tract and can occur in the large or small bowel.(2,14,15) It can be due to direct infiltration, intraluminal obstruction or external obstruction. This may occur due to tumour growth, adhesions, carcinomatosis, fecal impaction, pharmacotherapy and/or neuropathy.(2, 5, 9) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Assessment of Bowel Obstruction Ongoing comprehensive assessment is the foundation of effective management of bowel obstruction, including interview, physical assessment, medication review, medical and surgical review, psychosocial review, review of physical environment and the Document1 Page 99 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition appropriate diagnostics (see Table 1). Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family.(9) Table 1: Bowel Obstruction Assessment using Acronym O,P, Q, R, S, T, U and V * O P When did it begin? Have you had this before? Onset Provoking / What brings it on? What makes it better? What makes it worse? Palliating Q R Quality Region / What does it feel like? Can you describe it? Is the pain constant, colicky or crampy? Where is it? Does it spread anywhere? Radiation S T U Severity Treatment Understanding/ What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right Now? At Best? At Worst? On Average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom nausea/vomiting, pain, bloating, early satiety, hiccups, anorexia, constipation/diarrhea? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) · · · · Plain abdominal films may demonstrate dilated loops of bowel, air and fluid levels, fecal impaction and/or the obstruction.(1, 5, 9, 11) Gastrograffin contrast studies may further elucidate the point of obstruction and is preferred over barium, because barium can interfere with other studies.(1) CT scans may be required to determine the extent of the disease and help plan appropriate further treatments.(1) It is difficult to differentiate between partial and complete obstruction.(1, 5, 14) Document1 Page 100 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · The functional adrenal insufficiency in cancer may contribute to intestinal obstruction in patients with carcinomatosis peritonei.(16) Recommendation 2 Diagnosis Identifying the underlying etiology of bowel obstruction is essential in determining the interventions required. The type of obstruction, the condition of the patient and the predicted prognosis determine the treatment plan for the obstruction.(12, 14) Clinical symptoms: · · · · · · · · · Pain may be constant, crampy or colicky(1,3,11,13,16) resulting from the accumulation of secreted bowel fluid.(2,5,8) Suspect bowel strangulation if refractory to opioid analgesics.(5) Abdominal distension.(2, 5, 11, 16) Nausea and vomiting are eventually present but may vary in their intensity based on the level of the obstruction and the degree of compromise of bowel patency. In obstructions of the stomach, duodenum, pancreas or jejunum, vomiting will develop early and in large volumes.(1, 2, 5) Bowel sounds are usually altered and may be tympanic, high pitched, diminished or absent.(5, 9) Abdominal exam may demonstrate visceral or peritoneal irritation or may prove benign.(14) In complete obstruction there will be an absence of feces and flatus.(1, 5, 11) Fatigue.(11) Anorexia.(11) Diarrhea with partial obstruction (overflow diarrhea).(2, 5) Causes of Bowel Obstruction(9) Tumour mass Single or multiple Invasion and blockage of bowel (apple core) Extrinsic compression Constipation Impacted feces, obstipation Adhesions Postoperative Malignant Postradiation Volvulus Around tumour Around adhesions Around fistula Ileus Infection, peritonitis Drugs Peritonitis Infection, bleeding Massive ascites Document1 Page 101 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 3 Education The patient and family should be involved in discussions. Information should be reinforced so that appropriate decisions regarding disease modifying or symptom modifying therapies can be made.(3, 9, 13) Recommendation 4 · · · · · · · Treatment: Nonpharmacological Acute or initial treatment may include; keeping patient NPO, administering intravenous or subcutaneous fluids and performing nasogastric tube drainage. Nasogastric tube drainage should be an intermittent and temporary measure for initial treatment and decompression or while waiting to make other treatment decisions.(1, 2, 47, 914) Hydration should be considered in patients where dehydration causes agitated confusion or results in renal failure causing opioid metabolite accumulation leading to myoclonus or seizure(5, 6, 14) and should be considered on an individual basis.(2) Total parenteral nutrition should only be considered for the patient who would have clinical or lifeextending benefit. It is not recommended for most terminally ill patients(5, 9) and is best used in patients with a true long term prognosis.(13) Good mouth care and ice chips should be given for dry mouth.(2, 9, 13) Nasal care should be provided to patients who have a nasogastric tube inserted.(14) Support should be offered to patient and family as they confront the terminal nature of the disease.(9, 13, 14) Give small, low residue meals for patients with controlled nausea and vomiting.(2) Surgical Options: · The rate of inoperable patients ranges from 6% to 50%.(6, 10) · While surgery is the primary treatment for malignant bowel obstruction, not every patient will be a suitable candidate because of poor prognosis or advanced disease.(1, 9) · Surgery should be avoided in patients exhibiting: palpable abdominal and pelvic mass, ascites exceeding three litres, multiple obstructive sites and preoperative weight loss of greater than nine kilograms.(4, 6, 12, 17) · Interventions may include resection, bypass, stenting and venting gastric or jejunal tubes(4) and should be considered when symptoms have not been relieved after 48 to 72 hours of conservative medical management.(1, 9) Stenting and gastric or intestinal venting using percutaneous endoscopic gastrostomy tubes (PEG) are less invasive, generally well tolerated and can be done under sedation.(37, 12, 1820) · Mortality from surgery may approach 30% hence careful clinical judgment must be exercised and involving other disciplines and family is advisable.(1, 9, 17) · Prognosis, disease progression, patient’s wishes and comorbidities must be considered.(1) Document1 Page 102 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 5 Treatment: Pharmacological Treatment should always be parenteral as absorption via PO route is variable. · · · · · · · · Corticosteroids for inflammation dexamethasone 4 to 16 mg S.C. daily for incomplete or small bowel obstruction.(1, 57, 9) These were found to work better in patient populations that were not already taking steroids prior to the obstruction(7) and should be discontinued if the patient does not respond to steroid treatment within 4 to 5 days.(13) Antiemetics for nausea – combinations work best.(5, 9, 17) See Northern Health Hospice Palliative Care Symptom Guidelines for Nausea and Vomiting. Motility agents to stimulate bowel in cases of incomplete obstruction – metoclopramide 5 to 20 mg S.C. q.i.d.(5, 6, 9, 17) It is contraindicated in complete bowel obstruction.(5, 6, 13) Antimotility agents may have a role in complete obstruction hyoscine butylbromide 10 to 20 mg S.C. q.i.d.(1, 2, 11, 21, 22) Antisecretory agents octreotide 50150 mcg S.C. t.i.d.(5, 9) or 300 to 900 mcg by continuous S.C. infusion.(2, 57, 10, 11, 21) Octreotide was found to be more effective than hyoscine butylbromide in relieving gastrointestinal symptoms of advanced cancer patients.(21) In another study, octreotide resulted in significantly reduced gastrointestinal secretions by the second day of treatment(10) and it was also shown to reduce levels of nausea and pain when compared to scopolamine butylbromide(10) or hyoscine butylbromide.(11) Analgesics for pain may be given via S.C. or I.V. or transdermal route.(1, 5, 7, 9, 10, 21) Analgesics should not be avoided fearing aggravating an obstruction.(7) Cathartics via rectal route in cases of fecal impaction.(9) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using bowel obstruction terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Ripamonti C, Mercadante S. Pathophysiology and management of malignant bowel obstruction. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York Oxford University Press Inc., New York 2005. p. 496507. 2. Baines MJ. ABC of palliative care: Nausea, Vomiting and intestinal obstruction. British Medical Journal. 1997 November 1;315:114850. 3. WredeSeaman LD. Management of Emergent Conditions in Palliative Care. Primary Care: Clinics in Office Practice. June 2001;28(2):317 28. 4. Jolicoeur L, Faught W. Managing bowel obstruction in ovarian cancer using a percutaneous endoscopic gastrostomy (PEG) tube. Canadian Oncology Nursing Journal. 2003 April 13;13(4):2125. 5. Rousseau P. Management of Malignant Bowel Obstruction in Advanced Cancer: A Brief Overview. Journal of Palliative Medicine. 1998 November 1;1(1):6572. 6. Frank C. Medical management of intestinal obstruction in terminal care. Canadian Family Physician. 1997 Document1 Page 103 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition February;43:25965. 7. Laval G, et al. Protocol for the Treatment of Malignant Inoperable Bowel Obstruction: A Prospective Study of 80 Cases at Grenoble University Hospital Center. Journal of Pain & Symptom Management. 2006 June 6;31(6):50212. 8. Ross DD, Alexander CS. Management of Common Symptoms in Terminally Ill Patients: Part II Constipation, Delirium and Dyspnea. American Family Physician. September 15, 2001;64(6):1019 26. 9. Downing GM. Bowel Obstruction. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 3339. 10. Ripamonti C, Mercadante S, Groff L, Zecca E, DeConno F, Casuccio A. Role of Octreotide, Scopolamine Butylbromide and Hydration in Symptom Control of Patients with Inoperable Bowel Obstruction and Nasogastric Tubes: A Prospective Randomized Trial. Journal of Pain & Symptom Management. 2000 January 1;19(1):2334. 11. Mystakidou K, Tsilika E, Kalaidopoulou O, Chondros K, Georgaki S, Papadimitriou L. Comparison of Octreotide Administration versus Conservative Treatment in the Management of Inoperable Bowel Obstruction in Patients with Far Advanced Cancer: a Randomized, DoubleBlind Controlled Clinical Trial. Anticancer Research. 2002;22:118792. 12. Miller G, Boman J, Shrier I, Gordon P. SmallBowel Obstruction Secondary to Malignant Disease: An 11year Audit Canadian Journal of Surgery. 2000 October;43(5):3538. 13. Librach SL, Horvath AN, Langlois EA. Malignant bowel obstruction. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. p. 21327. 14. Letizia M, Norton E. Successful Management of Malignant Bowel Obstuction. Journal of Hospice and Palliative Nursing. JulySeptember 2003;5(3):1528. 15. BC Cancer Agency Professional Practice Nursing. Alert Guidelines: Bowel Obstruction. [cited 2006 April 2006]; Available from: http://www.bccancer.bc.ca/HPI/Nursing/References/TelConsultProtocols/BowelObstruction.htm 16. Poon D, et al. Adrenal Insufficiency in Intestinal Obstruction from Carcinomatosis Peritonei A Factor of Potential Importance in Symptom Palliation. Journal of Pain & Symptom Management. 2005 April 4;29(4):4118. 17. Brooksbank MA, Game PA, Ashby MA. Palliative venting gastrostomy in malignant intestinal obstruction. Palliative Medicine. 2002;16:5206. 18. Xinopoulos D, et al. Stenting or stoma creation for patients with inoperable malignant colonic obstuctions? Surgical Endoscopy. 2004 January 23;18:4216. 19. Fiori E, et al. Palliative Management of Malignant Rectosigmoidal Obstruction. Colostomy versus Endoscopic Stenting. A Randomized Prospective Trial. Anticancer Research. 2004;24:2658. 20. Haluszka O. Palliative Gastroenterology. Seminars in Oncology. 2005;32:1748. 21. Mercadante S, Ripamonti C, Casuccio A, Zecca E, Groff L. Comparison of octreotide and hyoscine butylbromide in controlling gastrointestinal symptoms due to malignant inoperable bowel obstruction. Support Care Cancer. 2000;8:18891. 22. Dean M, Harris JD, Regnard C, Hockley J. Bowel Obstruction. Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 714. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 104 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition NAUSEA AND VOMITING Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Depending on the review or study these symptoms occur in up to 90% of palliative care patients. In the majority of patients this can be successfully managed.(111) Scope The guideline provides strategies for the assessment and management of adults (age 19 years and older) living with advanced life threatening illness and experiencing the symptoms of nausea and vomiting. This guideline does not address disease specific approaches in the management of nausea and vomiting. Definition of Terms Nausea is expressed as an unpleasant subjective sensation as a result from stimulation of the gastrointestinal lining, the chemoreceptor trigger zone in the base of the fourth ventricle, the vestibular apparatus, or the cerebral cortex. Vomiting is an observable neuromuscular reflex that constitutes a final common pathway after stimulation of one or more of these regions. Vomiting can occur without nausea, and nausea does not always lead to vomiting. Both these symptoms, together or alone, can be very disruptive and distressing for patients and families.(12) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Assessment of Nausea and Vomiting Ongoing comprehensive assessment is the foundation of effective nausea and vomiting management, including interview, physical assessment, medication review, medical and surgical review, psychosocial and physical environment review and appropriate diagnostics(3, 5, 6, 10, 1320)(see Table 1). Document1 Page 105 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1: Nausea and Vomiting Assessment using Acronym O,P,Q R,S,T,U and V * O P Onset Provoking / When did it begin? How long does it last? How often does it occur? Is it there all the time? What brings it on? What makes it better? What makes it worse? Palliating Q R What does it feel like? Can you describe it? Quality Region / Do you have nausea with or without vomiting? Radiation S T U Severity Treatment What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? Understanding/ How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Recommendation 2 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. Intervention aimed at reducing nausea and vomiting must take into account the cause (often multifactorial) of the symptoms and the central emetogenic pathways and their corresponding neurotransmitter receptors.(2, 5, 810, 12, 13, 16 19, 2126) The Integrative Vomiting Center (IVC) or Emesis Center is stimulated by all of the pathways (see Appendix A) which in turn initiates nausea and vomiting. Document1 Page 106 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 2: Diagnosis: Determining the cause of nausea and / or vomiting Common Causes Clinical Picture Principle Site of Action Symptoms of drug toxicity or underlying disease plus nausea as the prominent symptom. Nausea usually not relieved by vomiting. Chemotrigger Zone(CTZ) Dopamine (D2), Serotonin receptor antagonist (5HT3) Epigastric pain, fullness, acid reflux, early satiety, flatulence, hiccup, intermittent nausea relieved with vomiting. Altered bowel habit, pain may occur with oral intake. Vomitus may be large volume and fecal smelling. Vagal & sympathetic afferent nerve pathways. Dopamine (D2), Serotonin receptor antagonist (5HT3) and 5HT4 receptors H2 receptors Acetylcholine Headache +/ cranial nerve signs, (diurnal). Vomiting often without nausea. Histamine (H1) receptors Chemical • Drugs (opioids, digoxin, steroids, antibiotics, anticonvulsants,cytotoxics) • Biochemical (hypercalcemia, uremia, organ failure) • Toxins (tumour factors, infection, drug metabolites, radiation, ischemic bowel, food poisoning) Gastrointestinal Tract–Vagal • Gastric irritation (ASA, NSAIDs, steroids, antibiotics, blood, ETOH, stress, radiotherapy) • Obstruction (partial or complete) • Constipation • Gastric stasis • Mass effect (GI, GU, hepatic distention, carcinomatosis) • Anatomic / Structural CNS • Increased Intracranial Pressure (brain metastases, infectious meningitis, cerebral edema, bleeding) • Psychological (fear, anxiety, pain) Anticipatory nausea / vomiting to sights, smells, etc. Vestibular • Motion sickness • Cerebellar tumour Recommendation 3 Nausea +/ vomiting with movement. Histamine (H1) receptors Acetylcholine Education Nausea and/or vomiting can be distressing to experience and witness. Providing information and education is foundational to enhance the patient and family’s ability to cope.(8, 13, 16, 20, 27) Document1 Page 107 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · Explain to the patient / family what is understood about the multiple triggers of nausea and / or vomiting and that it may take many strategies together to make a difference.(1) Consult with a Clinical Dietician and provide dietary advice. o Cut out intolerant foods.(1, 4, 6, 12) o Restrict intake when gastric distension is a factor. Start with sips, ice chips or popsicles, after nausea settled; gradually increase from fluids to semi solid to full food. If nausea recurs, step back until nausea resolves.(1, 15) o Avoid spicy, fatty and salty foods, or ones with strong odours.(6, 13, 14) o Avoid mixing liquids and solids.(12, 14, 15) o Use small frequent, bland meals when hungry.(6, 1215, 20, 24, 25) o Drinking cool, fizzy drinks.(4) o Avoid lying flat after eating.(12, 20) Recommendation 4 · · · Treatment: Nonpharmacological Environmental modification – eliminate strong smells and sights and use air deodorizers or fresheners.(4, 6, 8, 1215, 18, 20, 24) Maintain good oral hygiene, especially after episodes of vomiting.(3, 6, 13, 14, 18, 20) Acupuncture or acupressure point have been found to have limited benefit.(5, 15, 20, 27) · · · Visualization or hypnosis.(8, 15, 25, 27) Distraction.(4, 8, 14, 18, 20) Consult with Social Worker, Spiritual Practitioner, Physiotherapist, Occupational Therapist, Counsellors for psychosocial care, anxiety reduction.(12, 18, 27) Recommendation 5 · · · Treatment: Pharmacological Nausea is mediated by several neurotransmitters: the four main being; serotonin (5HT3), dopamine (D2), acetylcholine (Ach) and histamine (H1).(1, 4, 8, 10, 11, 15, 19, 23, 2628) (see Appendix A) Select antiemetics according to the etiology of nausea, vomiting and site of action of mediation.(1, 4, 6, 8, 1012, 14, 16, 19, 20, 23, 2628) Treatment recommendations Select antiemetic according to etiology, if the nausea is not controlled: o Metoclopramide is the usual first choice as it targets common causes of nausea in advanced diseases. o Titrate up antiemetics to their full dose before adding another drug.(25) o If nausea is not controlled with a specific antiemetic, add another antiemetic from another group if nausea continues for 48 hours, but do not stop the initial agent.(6, 10, 14, 27) o Consider combinations but monitor overlapping toxicities.(1, 14) o Use regular dosing of antiemetics if experiencing constant nausea and / or vomiting.(4, 27) o Antiemetics should be prescribed as a regularly scheduled dose with a breakthrough dose.(4, 27) Document1 Page 108 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition o All medications need to be individually titrated and a variety of routes and combinations of medications may be used to alleviate nausea.(6, 18, 25) o Give antiemetics prophylactically to prevent nausea with high dose opioids and chemotherapeutic agents.(1, 14, 27) o Ondansetron and aprepitant, although useful in chemotherapy and radiation induced nausea is considered as a fourth line therapy in chronic nausea and is therefore not covered by the BC Palliative Benefits Program.(29) Drug Route Dose Range Frequency Metoclopramide S.C. or PO or I.V. 10 to 20 mg q6h Domperidone PO 10 to 20 mg Haloperidol S.C. or PO or I.V. 0.5 to 2.5 mg Methotrimeprazine PO S.C. 6.25 to 12.5 mg 6.25 to 25 mg Prochlorperazine PO Rectal I.M. or I.V. 2.5 to 10 mg 10 mg 10 mg 6.25 mg t.i.d or q.i.d. q6h to q24h q4h to q24h q4h to q24h q4h to q6h q4h to q6h q3h to q6h ChlorproMAZINE PO or S.C. or I.M. q8h Olanzapine PO or I.M. 2.5 to 5 mg Daily DimenhyDRINATE PO or S.C. or I.M. or I.V. 25 to 50 mg q4h to q6h Promethazine PO or S.C. or I.M. 6.25 mg q8h Dexamethasone PO or S.C. or I.V. 4 to 24 mg daily or b.i.d. or t.i.d. Scopolamine Patch Atropine Transdermal 1.5 mg patch Every third day S.C. 0.4 to 0.8 mg q4h to q6h Ondansetron PO or I.V. 8 mg q8h to q24h Granisetron PO 1 mg q12h Dronabinol PO 2.5 to 15 mg q4h to q8h Nabilone PO 1 to 2 mg Octreotide S.C. 50 to 250 ug to 3 hrs pre then q8h to q12h post chemotherapy t.i.d. Lorazepam PO or SL or S.C. or I.V. 0.5 to 2 mg q4h to q24h Aprepitant PO 125mg prechemo, 80mg daily postchemo x 2 Document1 Page 109 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition days References Information was compiled using the CINAHL, Medline (1996 to March 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews / systematic reviews, clinical trials, case studies and guidelines / protocols using terms associated with nausea and vomiting in conjunction with palliative / hospice / end of life / dying. 1. Downing M. Nausea and Vomiting. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, British Columbia, Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 317 33. 2. Herndon CM, Jackson II KC, Hallin P, A. Management of Opioid Induced Gastrointestinal Effects in Patients Receiving Palliative Care. Pharmacotherapy. February 2002;22(2):240 50. 3. Yates R, Lyons M, Horstman A. Symptom control in advanced cancer. Journal of the American Academy of Physician Assistants. October 2003;16(10):40 52. 4. Rousseau P. Nonpain Symptom Management in the Dying Patient. Hospital Physician. 2002 Hospital Physician;38(2):51 6. 5. Pan CX, Morrison SR, Ness J, FughBerman A, Leipzig RM. Complementary and Alternative Medicine in the Management of Pain, Dyspnea, and Nausea and Vomiting Near the End of Life: A Systematic review. Journal of Pain and Symptom Management. December 13, 1999;20(5):374 87. 6. Tyler LS, Lipman AG. Nausea and Vomiting in Palliative Care. Evidenced Based symptom Control in Palliative Care: Systematic Reviews and Validated Clinical Practice Guidelines for 15 Common Problems in Patients with Life Limiting Disease. 2000;8(1):163 81. 7. Solano JP, Gomes B, Higginson IJ. A Comparison of Symptom Prevalence in Far Advanced Cancer, AIDS, Heart Disease, Chronic Obstructive Pulmonary Disease and Renal Disease. Journal of Pain and Symptom Management. June 13, 2005;31(1):58 69. 8. Doorley J, Hobbs M. The use of Selective Serotonin Antagonists in the Palliation of Intractable Nausea. Clinical Nurse Specialist: The Journal for Advanced Nursing Practice. November/December 2004;18(6):282 4. 9. Owens DA. Haloperidol as an Antiemetic. Journal of Hospice and Palliative Nursing. January/February 2005;7(1):7 8. 10. Currow DC, Coughlan M, Fardell B, Cooney NJ. Use of Ondansetron in Palliative Medicine. Journal of Pain and Symptom Management. May 5, 1997;13(5):302 7. 11. Critchley P, Plach N, Grantham M, Marshall D, Taniguchi A, Latimer E. Efficacy of Haloperidol in the Treatment of Nausea and Vomiting in the Palliative Patient: A Systematic Review. Journal of Pain and Symptom Management. August 2001;22(2):631 4. 12. Paolini CA. Symptoms Management at the End of Life. The Journal of the American Osteopathic Association. October 2001;101(10):609 15. 13. Wheeler MS. Palliative Care is more than Pain Management. Home Healthcare Nurse. April 2004;22(4):250 5. 14. Ladd LA. Nausea in Palliative Care. Journal of Hospice and Palliative Nursing. April June 1999;1(2):67 70. 15. Haughney A. Nausea & Vomiting in EndStage Cancer. American Journal of Nursing. November 2004;104(11):40 8. 16. Thompson I. The management of nausea and vomiting in palliative care. Nursing Standard. September 24, 2004;19(8):46 53. 17. Bentley A, Boyd K. Use of clinical pictures in the management of nausea and vomiting: a prospective audit. Palliative Medicine. May 2001;15(3):247 53. 18. Close H. Nausea and vomiting in terminally ill patients: towards a holistic approach. Nurse Prescribing. February 1, 2003;1 (1):22 6. 19. Mannix KA. Palliation of nausea and vomiting. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 459 68. 20. de Kock I. Nausea and vomiting. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. 21. Pinkowish MD, Bruera Ec, Byock Ic. Management of pain and other discomfort. Patient Care. November 15, 2000:38 71. 22. WredeSeaman LD. Management of Emergent Conditions in Palliative Care. Primary Care: Clinics in Office Practice. June 2001;28(2):317 28. Document1 Page 110 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 23. Ross DD, Alexander CS. Management of Common Symptoms in Terminally Ill Patients: Part I. Fatigue, Anorexia, Cachexia, Nausea and Vomiting. American Family Physician. September 1, 2001;64(5):807 14. 24. Esper P, Heidrich D. Symptom Clusters in Advanced Illness. Seminars in Oncology Nursing. February 2005;21(1):20 8. 25. Han P, Arnold B, von Gunten CF. The Challenge of Chronic AIDSRelated Nausea and Vomiting. Journal of Palliative Medicine. March 2001;4(1):65 8. 26. Bruera E, Neumann CM. Management of specific symptom complexes in patients receiving palliative care. CMAJ: Canadian Medical Association Journal 1998 Jun 30; 158(13): 171726 (44 ref). 27. ONS. Nausea and vomiting Detailed PEP (Putting Evidence into Practice) Card. [Evidence based guidelines] May 2006 [cited; Available from: http://www.ons.org/outcomes/resources/nausea.sht mL 28. Spiller JA, Fallon M. The use of Scopoderm in palliative care. Hospital Medicine (London) 2000 Nov; 61(11): 782 4 (13 ref). 29. British Columbia Ministry of Health Services. BC Palliative Care Benefits Program Physician Guide. 2005 [cited 2006 July 24th, 2006]; Available from: http://www.health.gov.bc.ca/pharme/outgoing/palliative_physguide.pdf Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 111 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix A Nausea & Vomiting Pathways and Antiemetics Copyright notice: with permission, page 319, Medical Care of the Dying (2006), Victoria Hospice Society Document1 Page 112 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition NUTRITION & CACHEXIA Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Up to 80% of patients living with and dying from advanced life threatening illness experience the symptoms of cachexia and/or anorexia.(16) Cachexia and anorexia are common multifactorial and distressing complications of terminal illness, especially cancer and HIV/AIDS. The clinical signs are anorexia and weight loss. They may prevent further interventions such as surgery and chemotherapy, and causes families to feel helpless as they perceive their loved ones “starving to death”. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of cachexia and/or anorexia. This guideline does not address disease specific approaches in the management of cachexia and/or anorexia. Definition of Terms Anorexia loss of appetite and resulting reduced caloric intake. Cachexia – involuntary weight loss of more than 10% of premorbid weight, associated with loss of muscle and visceral protein and lipolysis (the breakdown of fat stored in fat cells). Cachexia may not correlate with anorexia. The anorexiacachexia syndrome is usually defined in terms of primary or secondary causes. Primary cause is related to changes (metabolic and neuroendocrine) directly associated with underlying disease and an ongoing inflammatory state. Secondary causes are aggravating factors (fatigue, pain, dyspnea, infection, etc) that contribute to weight loss.(13, 613) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Document1 Page 113 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 1 Assessment of Cachexia and Anorexia Ongoing comprehensive assessment is the foundation of effective cachexia and anorexia management, including interview, physical assessment, medication review,medical and surgical review and psychosocial and physical environment review and appropriate diagnostics(13, 7, 9, 12, 1417) (see Table 1). Table 1: Nutrition / Cachexia Assessment using Acronym O,P,Q,R,S,T,U and V * O P Onset Provoking / When did you notice your weight loss or lack of appetite? How long does it last? How often does it occur? Is it there all the time? What brings it on? What makes it better? What makes it worse? Palliating Q R Quality Region / What does it feel like? Can you describe it? How much weight have you lost? How much do you eat and drink? Radiation S T U Severity Treatment Understanding/ What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Document1 Page 114 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 2 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. The most significant intervention in the management of cachexia and anorexia is identifying underlying cause(s) and treating as appropriate (see Table 2). While underlying cause(s) may be evident, treatment may not be indicated, depending on the stage of the disease. Intervention aimed at reducing cachexia and anorexia must take into account the cause (often multifactorial) of the symptoms.(14, 7, 8, 11, 1321) Table 2: Causes of Cachexia Causes of Cachexia Patients Affected Interventions Cancer byproducts Cytokines; tumour necrosis factor, interleukin 1, leptin Megestrol acetate, NSAIDS, corticosteroids Depression or delirium May cause or be caused by anorexia/cachexia Dysphagia Head, neck or esophageal tumours Haloperidol, antidepressants, psychosocial support, counseling Enteral feeding (gastrostomy preferred), stent, swallowing assessment, laser / radiation, pain control with topical anesthetics or systemic analgesics Gastrointestinal disturbances Obstruction or constipation Bowel regime, domperidone, metoclopramide or peripheral opioid antagonists and interventions for obstruction Malabsorption syndrome Fats and carbohydrates not metabolized/absorbed Corticosteroids, megestrol acetate, omega 3 fatty acids Treatment toxicities: mucositis, nausea/vomiting Radiation, chemotherapy, medications Treat according to toxicity Uncontrolled symptoms: Patients with advanced pain, dyspnea, disease processes constipation, and nausea/vomiting Control symptoms to increase appetite and quality of life Xerostomia, altered oral condition or taste Saliva substitutes, good oral hygiene and nutrition, zinc supplements Document1 Infection, poor hygiene, dehydration, medication, taste bud alteration Page 115 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 3 Education Early counseling regarding nutritional aspects is vital. Emphasize that oral intake will lessen over time (functional dysphagia) – explain the metabolic abnormalities causing anorexia. Assist families and caregivers to understand and accept the benefits and limits of treatment interventions and to look at alternate ways to nurture the patient (oral care, massage, reading, conversing). This will help to decrease the feelings of helplessness for these individuals. Advise families that pressuring their loved one to eat increases anxiety and stress for them all and can worsen symptoms of nausea and vomiting.(13, 7, 17) Recommendation 4 · · · · Treatment: Nonpharmacological Oral nutrition is the ideal with emphasis on “what one likes” rather than “what is right or of value” nutritionally. As the illness progresses, educate that intake will decrease and that this is natural. Ice chips, small sips of beverages and good mouth care becomes the norm.(1, 7, 11, 20, 22) Consider hypodermoclysis to correct symptoms related to dehydration when there are symptoms that could be relieved by parenteral fluids and will improve quality of life.(1) See Northern Health Hospice Palliative Care Symptom Guideline for Dehydration. Enteral feeding may be appropriate in patients who have difficulty swallowing and who have an appetite and reasonable quality of life; consider a gastrostomy rather than a nasogastric tube for comfort and body image; Gtubes also provide drainage should total bowel obstruction occur. There is a risk of aspiration pneumonia and diarrhea. Patients with secondary etiologies benefit from this type of feeding.(1, 2, 13, 18, 20) Consultation with dietician and/or counselor and family education is critical.(1, 2, 17, 20) · Total parenteral nutrition is the exception thus should only be considered in exceptional situations – multiple studies have found no benefit on mortality or morbidity rates.(13, 12, 13, 16, 17, 19, 22, 23) Recommendation 5 Treatment: Pharmacological Goal of treatment should be to conserve or restore best quality of life; to control symptoms that cause aggravating symptoms or distress; emphasis should not be solely nutrition and should be determined prior to initiation of treatment. A multidisciplinary approach is needed considering prognosis, patient and family wishes.(2, 3, 7, 9, 11, 14) Most Commonly Used: Document1 Page 116 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · Metoclopramide should be considered when chronic nausea occurs in association with cachexia because of the high incidence of autonomic failure with resulting gastroparesis. Metoclopramide 10 mg q4 to 8h.(2, 11, 14) Megestrol acetate may be useful in treating anorexia in patients with expected survival time of months or for end stage renal patients for uremic syndrome. Side effects are usually mild (and dose related) but can include edema, venous thromboembolic events, hypertension, alopecia, adrenal suppression, hypercalcemia and cushingoid fat distribution. Megestrol acetate 160 to 800 mg per day, titrate.(2, 3, 6, 7, 911, 13, 14) Corticosteroids may increase appetite, strength and promote a sense of well being; effects last about 2 to 4 weeks making it appropriate for those whose life expectancy is weeks. Dexamethasone 4 to 8 mg per day – titrate for increased appetite.(2, 3, 5, 7, 11, 13, 14) Less Commonly Used: · · · · · · NSAIDS like ibuprofen and cox inhibitors have been shown to have some beneficial effect on anorexia/weight loss by mediating the inflammatory response of cytokines. (10, 14, 19) Ibuprofen 400 mg t.i.d.(10) or indomethacin 50 mg b.i.d.(19) Melatonin has been shown to have some effect on weight loss by mediating circulating tumour necrosis factor.(4, 14) Melatonin 20 mg daily at bedtime.(4) Omega 3 fatty acids have been shown to normalize metabolism and stabilize weight. (3, 7, 14, 19) Eicosapentaenoic acid (EPA) 2.2 grams daily and docosahexaenoic acid (DHA) 0.96 grams daily.(24) Dronabinol may decrease nausea, stimulate mood, and appetite but is not proven effective in preventing weight loss. 5 mg daily.(2, 3, 7, 13) Adenosine Triphosphate has been shown to have some positive effect on weight gain but needs further study.(21) Cyproheptadine may cause mild appetite increase but does not prevent progressive weight loss in advanced cancer, has sedative side effect.(2, 7, 13, 14) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines / protocols using nutrition/cachexia/anorexia terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Syme A, Fimrite A. Gastrointestinal. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 301 6. 2. Walker P, Bruera E. Anorexia Cachexia Syndrome. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. p. 75 88. 3. Fainsinger RL, Pereira J. Clinical assessment and decisionmaking in cachexia and anorexia. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 533 46. Document1 Page 117 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 4. Lissoni P, Paolorossi F, Tancini G, Barni S, Ardizzoia A, Brivio F, et al. Is There a Role for Melatonin in the Treatment of Neoplastic Cachexia? European Journal of Cancer. March 28, 1996;32A(8):1340 3. 5. Bruera E, Roca E, Cedaro L, Carraro S, Chacon R. Action of Oral Methylprednisolone in Terminal Cancer Patients: A Prospective Randomized DoubleBlind Study. Cancer Treatment Reports. July/August 1985;69(7 8):751 4. 6. Salacz M. Megestrol Acetate for Cancer Anorexia Cachexia. Educational Material Details 2003 October 2003; Available from: http://www.aahpm.org/cgibin/wkcgi/view?status=A%20&search=256&id=504&offset=0&limit=25 7. Syme A. Cachexia Anorexia Syndrome. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 307 10. 8. Strasser F. Nutrition. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 520 33. 9. Tomiska M, Tomiskova M, Salajka F, Adam Z, Vorlicek J. Palliative treatment of cancer anorexia with oral suspension of megestrol acetate. Neoplasma. November 19, 2002;50(3):227 33. 10. McMillian DC, Wigmore SJ, Fearon KCH, O’Gorman P, Wright CE, McArdie CS. A prospective randomized study of megestrol acetate and ibuprofen in gastrointestional cancer patients with weight loss. British Journal of Cancer. May 28, 1998;79(3/4):495 500. 11. Paolini CA. Symptoms Management at the End of Life. The Journal of the American Osteopathic Association. October 2001;101(10):609 15. 12. ONS. Measuring Oncology NursingSensitive Patient Outcomes: Evidenced Based Summary: Nutritional Status. 2005 March 2005; Available from: http://www.ons.org/outcomes/Clinical/pdf/NutritionOverview.pdf http://www.ons.org/outcomes/Clinical/pdf/NutritionSummary.pdf 13. Yeomans WR. Hydration and Nutrition in Palliative Care. The Canadian Journal of CME.September 1997:111 5. 14. Bruera E, Swenney C. Pharmacological interventions in cachexia and anorexia. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 552 60. 15. Milne AC, Potter J, Avenell A, Cheskin LJ. Protein and energy supplementation in elderly people at risk from malnutrition. ACP Journal Club. May/June 2003;138(3):59. 16. Regional Palliative Care Program Clinical Practice Guidelines. Home Parenteral Nutrition and Cancer Selection Criteria for Patients with Advanced Cancer 2002; Available from: http://www.palliative.org/PC/ClinicalInfo/Clinical%20Practice%20Guidelines/PDF%20files/Home%20Parenteral.pdf 17. Ersek M. Artificial Nutrition and Hydration: Clinical Issues. Journal of Hospice and Palliative Nursing. October December 2003;5(4):221 30. 18. Skelly RH. Are we using percutaneous endoscopic gastrostomy appropriately in the elderly? Current Opinion in Clinical Nutrition and Metabolic Care. 2002;5:35 42. 19. Lundholm K, Daneryd P, Bosaeus I, Korner U, Lindholm E. Palliative Nutritional Intervention in Addition to Cyclooxygenase and Erythopoietin Treatment for Patients with Malignant Disease: Effects on Survival, Metabolism, and Function. Cancer. May 1, 2004;100(9):1967 77. 20. Cline D. Nutrition Issues and Tools for Palliative Care. Home Healthcare Nurse. 2006 January 2006;24(1):54 7. 21. Agteresch H, J, Dagnelie PC, van der Gaast A, Stijnen T, Wilson JHP. Randomized Clinical Trial of Adenosine 5’ Triphosphate in Patients with Advanced NonSmallCell Lung Cancer. Journal of the National Cancer Institute. February 16, 2000;92(4):321 8. 22. Davidson I, Richardson R. Dietary and nutritional aspects of palliative medicine. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 546 52. 23. Karetz RL. Parenteral Nutrition: Is it Oncologically Logical? Journal of Clinical Oncology. May 1984;2(5):534 8. 24. Barber M, McMillian DC, Preston T, Ross JA, Fearon KCH. Metabolic response to feeding in weightlosing pancreatic cancer patients and its modulation by a fishoilenriched nutritional supplement. Clinical Science. April 2000;98(Part 4):38999. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 118 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition PRINCIPLES OF PAIN ASSESSMENT Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. According to the 2006 Cancer Estimates 6080% of patients have pain in advanced stages and 2575% of patients die without good pain control. “Pain that is uncontrolled leads to a death that is without grace and dignity. It destroys the person who suffers it, breaks the family who witnesses, and brands the staff who passes by on the other side.” (A patient’s mother Nursing Times) Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing pain. This guideline does not address disease specific approaches in the management of pain. Definition of Terms Pain is “an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage” (1) The concept of Total pain encompasses the multidimensional factors that contribute to the patients experience of pain. It may include all of the following: Intellectual Pain, Emotional Pain, Interpersonal Pain, Financial Pain, Spiritual Pain, Bureaucratic Pain, and Physical Pain.(2) The patient’s experience of pain is expressed within the context of the illness, and the personal, emotional, social, cultural, and spiritual orientation of the individual. Suffering, like pain, is subjective. Suffering is characterized as a person’s evaluation of the significance of an event such as pain or the meaning of an event in relationship to self and to the quality of life. “Pain is what the patient says it is, and exists whenever the patient says it does.”(3) Standard of Care 1. Assessment 2. Classification 3. Establish a Plan 4. Education Document1 Page 119 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 1 Assessment of Pain Ongoing comprehensive assessment is the foundation of effective pain management, including interview, physical assessment, medication review, medical and surgical review, psychosocial review, review of physical environment and the appropriate diagnostics. (4) (see Table 1). Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family. Table 1: Pain Assessment using Acronym O, P, Q, R, S, T, U and V * O P When did it begin? How long does it last? How often does it occur? Onset Provoking / What brings it on? What makes it better? What makes it worse? Palliating Q R What does it feel like? Can you describe it? Quality Region / Where is it? Does it spread anywhere? Radiation S T U Severity Treatment What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? Understanding/ How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? *also include a Physical Assessment (as appropriate for symptom) Document1 Page 120 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · Goal of Pain Assessment o to capture the individual’s pain experience in a standardized way o to help determine type of pain and possible etiology o to determine the affect and impact the pain experience has on the individual and their ability to function. o basis on which to develop treatment plan to manage pain o to aid communication between interdisciplinary team members. · Self reporting should be the primary source of information when completing a pain assessment. Trust the client’s assessment of pain. Lack of pain expression does not necessarily mean absence of pain. (6) The exception for patient self reporting is with nonverbal, noncognizant persons (ie. the cognitively impaired) For these populations, behavioral observations that are validated by family and care givers are the primary source of information for a pain assessment. For the cognitively impaired patient, use the Abbey Pain Assessment (see Appendix 2.10 in the NH HPC Program Manual) and/or a visual or faces pain scale instead of verbal questions.(4) Body language should also be observed: facial expressions, verbalizations, behaviour during activity, movements and gestures. (6) In the cognitively impaired recognize pain as a possible cause of changes in function or behaviour: increased confusion, resistance to care, disruptive behaviour, aggression, changes in appetitie, changes in sleep pattern, asking for help, reduced mobility, social withdrawal. Screen all persons at risk for pain. Pain assessment should be completed by the primary care provider on admission to all sites/programs and reassessed on an ongoing basis (6) as there is always the potential for new or increasing symptoms as the patient nears the end of life. Once the presence of pain has been identified an initial comprehensive pain history must be completed. Use a validated measurement tool, such as the OPQRSTUV above, to ensure that complete, comprehensive, and consistent assessments are done. When pain is identified in more than one site, an assessment is completed for each site. (6) A comprehensive pain assessment should be redone if there is a significant change in the pain, any modification to the pain management plan, or if a new pain has been identified. Following analgesic administration, the assessment of pain severity on a scale of 0 10 using a pain scale would be the minimum assessment to be completed to monitor analgesic effectiveness in meeting patient’s goal. Use a standard pain scale matched to the patient’s cognitive and communication abilities ie. Visual Analogue Scale (VAS), Numeric Rating Scale (NRS 010), Faces Scale, or Verbal Scale. (6) Pain assessments should be documented so that all members of the care team will have a clear understanding of the pain. Location of documentation to be consistent within each care site. When efforts of the primary care providers do not relieve pain, a team conference (including patient and/or family) should be held and a referral (6) to the NH Hospice Palliative Care Team should be made. · · · · · · · · · Document1 Page 121 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 2 Classification of Pain Pain is classified by mode of origin and transmission to aid in choosing a management plan for pain relief (2,5) Nociceptive pain is due to the stimulation of nerve fibers that transmit signals in a normal way from nerve endings to brain centers. (2) · Somatic pain – pain originating from muscle, soft tissue or bone. It is usually well localized and described as deep, aching, or boring. It may be worse with movement. Some examples are bone metastases, osteoarthritis, and muscle/tissue damage. (2,5) · Visceral pain – pain originating from internal organs or viscera surrounding them. It is usually less well localized and can be referred. Often described as deep aching, cramping, or squeezing. Some examples are bowel obstruction, brain tumour, and appendicitis. (2,5) Neuropathic pain is the abnormal sustained stimulation of the nerve fibers that transmit signals from the nerve ending to brain center and/or from a dysfunction in the central nervous system. (2) · It can be dysesthetic pain – described as burning, electrical sensations or pins and needles and/or lancinating pain – described as stabbing, shooting, or hot poker (5) · Some examples are postherpetic neuralgia, spinal cord compression, diabetic neuropathy, plexopathies, phantom limb, or central pain from a stroke · Pain may exceed any observable injury and often requires multiple medications to obtain relief (See recommendation 14 in Northern Health Hospice Palliative Care Symptom Guidelines for Principles of Pain Management) Recommendation 3 Establish a Plan Using the pain assessment establish a plan that: · uses the most effective pharmacological and nonpharmacological interventions for the type of pain identified (see Northern Health Hospice Palliative Care Symptom Guidelines for Principles of Pain Management) · includes physical, psychological, and behavioral interventions · includes treatments and selection of analgesia/adjuvants which are individualized and consistent with the patients goals for pain relief. These goals may also relate to: o maintenance of dignity (6) o acceptable functional capacity (6) o quality of life (6) o capacity for adequate rest and sleep (6 o medication side effects minimal or at least tolerable (6 Assess and document the effectiveness of the plan on an ongoing basis. (6) Document1 Page 122 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 4 · · · · · Education It is important to explain to the patient and family that pain may get worse as the disease progresses; however, there are many options available for pain relief. Discuss the concept of pain prevention with the patient and family, in an effort to lessen the pain experience before pain becomes difficult to manage. Teach patients and families to report changes in pain, pain that is new and pain that does not improve after intervention. Some patients, particularly the elderly, may underreport pain because they: o Have not been taken seriously in the past (6) o fear being labeled a “complainer” (6) o want to appear stoic, an important characteristic in some cultures (4) o expect pain with aging, when in fact it is common but not a normal part of aging(6) o choose to avoid medications and side effects (6) Education for patient and family should occur regarding these concerns to ensure they report their pain in a trusting and caring environment. Include the patient and family in decision making to determine a care plan that values the patients wishes, emphasizing the shared goals of care. References 1. International Association for the Study of Pain, 1979 (912) 2. Downing M. Pain Etiology. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, British Columbia, Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 69114. 3. McCaffrey, M & Beebe, A.. Pain: Clinical manual for nursing practice.1989. St Luis: CV Mosby Co. 4. Downing M. Pain Assessment. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, British Columbia, Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 119155. 5. Eddy, B., Geddes, V., Lochbaum, J., Nixon, A., Spring, B., Tanner, M., Tuyp, R., Yearwood, L. Pain Management. In: Community Palliative Care Clinical Practice Guidelines. Vancouver Coastal Health, 2007. p.68 6. Harrigan Consulting. Best Practices for the Nursing Care of the Older Adult. Network of Excellence for Geriatric Services. Northern Health – Clinical Practice Guidelines – Assessment and Management of Persistent Pain – April 2005. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 123 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition PRINCIPLES OF PAIN MANAGEMENT Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of pain and requiring the use of opioid medication to control the pain. This guideline does not address disease specific approaches in the management of pain. Definition of Terms Opioid refers to drugs with morphine like actions, both natural and synthetic. Examples of opioids are: codeine, morphine, hydromorphone, oxycodone, fentanyl and methadone.(1) · Short acting opioid medications are also called immediate release (IR). These can come in oral, suppository, gel or parenteral formulations.(2) · Long acting opioid medications are also called sustained release (SR), controlled release (CR) or extended release (ER). These can come in oral or transdermal formulations.(1) · Total Daily Dose (TDD) is the 24 hour total of a drug that is taken including regular and breakthrough doses.(2) · Steady state is when the rate of drug availability and elimination equal one another.(1) · Breakthrough Dose (BTD) is an additional dose used to control breakthrough pain (a transitory flare of pain that occurs on a background of relatively well controlled baseline pain). It does not replace or delay the next routine dose. BTD is also known as a rescue dose.(2) Opioid titration has traditionally been referred to as adjusting the dosage of an opioid.(3, 4) It requires regular assessment of the patient’s pain, when and why it occurs as well as the amount of medication used in the previous 24 to 72 hour period.(2) Opioid rotation is switching one opioid for another. It is required for patients with inadequate pain relief and / or intolerable opioid related toxicities or adverse effects.(1, 5) Opioid withdrawal occurs when an opioid is discontinued abruptly. Withdrawal symptoms last for a few days and are generally the opposite of symptoms exhibited when the opioid was started.(1) Document1 Page 124 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Opioid naïve patient refers to an individual who has either never had an opioid or who has not received repeated opioid dosing for a 2 to 3 week period.(6) Opioid tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug’s effects over time.(7, 8) It is a known pharmacologic effect of opioids.(8) Tolerance to the analgesic effects of opioids is relatively uncommon.(7) Physiologic dependence is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug and / or administration of an antagonist.(8) Addiction is a primary, chronic, neurobiological disease, with genetic, psychosocial and environmental factors influencing its development and manifestations. It is characterized by behaviours that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm and craving.(9) NonOpioid is a term used to describe drugs that are structurally and functionally unrelated to opioids but whose primary indication is for the treatment of pain.(10) Examples are: acetaminophen, acetylsalicylic acid (ASA) or nonsteroidal antiinflammatory drugs (NSAIDs).(1) Adjuvant analgesics (sometimes known as coanalgesics) are medications whose primary indication lies elsewhere, but which have been found to be beneficial in the management of some types of pain. Commonly used adjuvants are: corticosteroids, antipsychotics, antidepressants, anticonvulsants and bisphosphonates. Other adjuvant therapies used include radiation, intrathecal and epidural analgesia, nerve blocks and surgery.(1) Standard of Care 1. Opioid Principles 2. Screen for Sensitivity or Allergy to Specific Opioids 3. Assessment of Pain 4. Diagnosis 5. W.H.O Principles 6. Opioids Formulations 7. Routes of Administration of Opioids 8. Adverse Effects of Opioids 9. Opioid Titration 10. Use of Long Acting Opioids 11. Opioid Rotation 12. Opioid Withdrawal 13. Treatment: Nonpharmacological 14. Treatment: Pharmacological 15. Nonopioids/Adjuvants/Coanalgesics Document1 Page 125 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 1 · · · · · · · · · · · · · · Opioids can and should be used for both cancer and noncancer pain where other measures, including nonopioid analgesics, are insufficient to control debilitating pain.(11) Opioids are the drugs of choice for moderate to severe pain associated with advanced illness.(1216) When the pain is only mild to moderate but expected to worsen, starting a stronger opioid may avoid another drug switch.(1) When introducing opioids for the older adult, the dose should be 1/2 to 1/3 of the regular adult dose – “start low, go slow” and carefully monitor for side effects (38) Longacting or sustainedrelease analgesic preparations should be used for continuous stable pain (16) after a titration period with short acting to determine opioid requirements. Medical use of opioids for pain associated with advanced illness rarely, if ever, leads to drug abuse or opioid addiction.(13) There is no ceiling or maximal recommended dose for strong opioids.(15) Large doses may be needed to manage pain associated with advanced illness.(8, 17) Use oral route whenever possible.(18) There is no perfect route of administration; the plan must be individualized to the patient and the setting.(1) When writing opioid orders, remember to order medications to cover the 3 “B’s” – Bowels, “Barfing” and Breakthrough.(2, 16, 17, 19) Consider opioid rotation if there are adverse effects from, or tolerance to, the current opioid.(2) It is not recommended to administer two different opioids (e.g., regular morphine with codeine or hydromorphone for breakthrough) at the same time(20) unless the duration of relief desired is not able to be achieved with one. For example, using IR opioids with fentanyl patches or sufentanil for incident pain when using long acting (SR) opioids. Meperidine has little use in the management of chronic pain and is rarely used in the palliative setting.(15, 21) Opioid use does not shorten survival.(16) Documentation of the use of opioids contributes to appropriate dosing and pain control.(22) Recommendation 2 · · · · Opioid Principles Screen for Sensitivity or Allergy to Specific Opioid Most “allergies” to morphine are not true allergies but rather adverse effects.(13) The only absolute contraindication to the use of an opioid is a history of a true hypersensitivity reaction.(16) Opioids cause histamine release with subsequent itch and rash, which is sometimes mistaken for an allergic reaction.(13) More potent opioids are less likely to release histamine.(35) Patients allergic to one opioid are not likely to be allergic to another opioid in a different structural class. (35) Document1 Page 126 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Phenylpiperidine class – meperidine, fentanyl, sufentanil, remifentanil o Diphenylheptane class – methadone, propoxyphene o Morphine class – codeine, morphine, hydrocodone, oxycodone, hydromorphone If there is a true history of allergy to codeine or morphine (natural occurring opioids), a semisynthetic opioid (such as hydromorphone or oxycodone) or a synthetic opioid (such as fentanyl or methadone) may be carefully tried with appropriate precautions.(17) The prevalence of true allergic reactions to synthetic opioids may be lower.(16) Education of and appropriate management of possible adverse effects of opioids help to avoid situations where patients and / or families assume that they are “allergic” or can never take a drug again.(2) o · · Recommendation 3 Assessment of Pain Ongoing comprehensive assessment is the foundation of effective management of pain using opioids, including interview, physical assessment, medication review, medical and surgical review, psychosocial review and review of physical environment.(16) Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family. See Northern Health Hospice Palliative Care Symptom Guidelines for Principles of Pain Assessment for direction on pain assessment. Assess patient and family fears and barriers around the use of opioids.(7, 16, 23) Recommendation 4 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. The most significant intervention in the management of pain is identifying underlying cause(s) and treating as appropriate. While underlying cause(s) may be evident, treatment of pain is always indicated, no matter what the stage of disease or while investigations are ongoing.(1) See Northern Health Hospice Palliative Care Symptom Guidelines for Principles of Pain Assessment for direction in classifying the etiology of the pain. Whether or not the underlying cause(s) can be relieved or treated, all patients will benefit from management of this symptom using education or medication. Document1 Page 127 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 5 W.H.O. Principles World Health Organization’s (WHO) Pain Relief Ladder for Cancer Pain(18) If pain occurs, there should be prompt oral administration of drugs in the following order: nonopioids (ASA and acetaminophen); then, as necessary, mild opioids (codeine); then strong opioids such as morphine or hydromorphone, until the patient is free of pain. Adjuvant drugs should be used for specific pain etiologies. To maintain freedom from pain, drugs should be given “by the clock”, that is every 3 to 6 hours (depending on the drug), rather than “on demand”. This threestep approach of administering the right drug at the right dose at the right time is inexpensive and 80 to 90% effective.(18) WHO’s Pain Relief Ladder Cancer Pain Step One: for very mild pain a nonopioid analgesic (such as acetaminophen or ASA) maybe adequate.(7, 18) Step Two: if the pain is moderately severe a weak opioid plus or minus appropriate adjuvant agent(s) may provide adequate analgesia.(7, 18) Step Three: for severe pain, or when it is expected that pain will become severe, it is best to start with a low dose of a strong opioid and titrate up the dose according to effect.(7, 18) from the Department of Knowledge Management, World Health A weak opioid is one that has a ceiling effect, which may be due to a low affinity for Organization, Geneva, Switzerland. opioid receptor sites.(1) Document1 Page 128 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition The W.H.O Principles can be summed up as follows:(7) • By mouth • By the clock oral route is the route of administration of choice. analgesic medications for moderate to severe pain should be given on a fixed dose schedule, not on an as needed basis. • By the ladder analgesics given per the W.H.O three step ladder. • For the individual the dosage must be titrated against the particular patient’s pain. • Use of adjuvants to enhance analgesic effects, to control adverse effects of opioids and to manage symptoms that are contributing to the patient’s pain (anxiety, depression or insomnia). • Attention to detail determine what the patient knows, believes and fears about the pain and things that can relieve it. Give precise instructions for taking the medication. Recommendation 6 Opioid Formulations Commonly used first line oral opioids include codeine, morphine, hydromorphone, and oxycodone. They share the following characteristics: · · · · Halflife of immediate release preparations is 2 to 4 hours with duration of analgesic effect between 4 to 5 hours when given at effective doses.(1, 8, 16) Most oral sustained release formulations have duration of analgesic effect of 8 to 12 hours.(16) Equianalgesic doses need to be calculated when switching from one drug to another, when changing routes of administration or both.(1) An equianalgesic table should be used as a guide in dose calculation. Due to incomplete crosstolerance clinicians should consider reducing the dose by 20 to 25% when ordering.(1) Document1 Page 129 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Comparison of Available Opioids: Opioid Codeine Morphine Oxycodone Hydromorphone Fentanyl Immediate release preparations 15 , 30 mg IR tablet Liquid: 5 mg per mL 5, 10, 30 mg IR tab Liquid: 1, 5, 10, 20, 50 mg per mL 5, 10, 20 mg IR tab Liquid: N/A 1, 2, 4, 8 mg IR tab Liquid: 1 mg per mL No IR tablet ** Parenteral solution may be given as sublingual dose Sustained release preparations 50,100,150, 200 mg SR tablets 12 Hour formulations: 10, 15 , 30, 60, 100, 200 mg SR 24 Hour formulations: 10, 20, 50,100 mg capsule 5, 10, 20, 40, 80 mg SR tablets 3, 6, 12 , 18, 24 , 30 mg SR capsules 12 , 25 , 50, 75 , 100 mcg patch Rectal No suppository 5, 10, 20, 30 mg suppositories No suppository 3 mg suppository No suppository Parenteral 30,60 mg/ mL 2, 10, 15 , 25 , 50 mg/ mL injection No injection 2, 10, 50 mg/ mL injection 50 mcg/ mL injection Relative potency: compared to 10 mg PO Morphine PO:100mg PO: 10 mg Parenteral: 5 mg PO: 6.7 mg (range 57.5mg) PO: 2 mg S.C., I.V.: 1 mg 50 to 100 mcg when administered sublingually Opioid Class Naturally occurring Semisynthetic Semisynthetic Semisynthetic Synthetic Comments: • Ceiling effect at 360 600 mg • Ineffective analgesic in a small percentage of patients as some lack an enzyme to convert codeine to morphine.(1, • In renal failure Metabolites may accumulate to toxic levels.(1) • Lower incidence of pruritus, sedation and nausea and vomiting.(1) Halflife is 2 to 4 hours with duration of analgesic action between 30 minutes and 4 hours **See Appendix A 13, 14, 21) Document1 Page 130 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Fentanyl Information (See Appendix A): · · · · · Fentanyl is 80 to 100 times more potent than morphine.(1, 14) A recent study reported less constipation and somnolence in patients using transdermal fentanyl compared to those using SR morphine.(1) Fentanyl’s high lipophilic properties provide a sufficient sublingual bioavailability of 90%, thus making it a suitable opioid for use sublingually.(1) Transdermal patches may not be appropriate for patients with fever, diaphoresis, cachexia, morbid obesity, ascites or opioidnaïve patients.(16) These conditions may have a significant effect on the absorption, blood levels and clinical effects of the drug.(16) See Appendix A for further fentanyl transdermal information Methadone Information (See Appendix B): · · · · The complexity in prescribing methadone prevents it being a firstline opioid.(1) The initiation of or switch to methadone for advanced cancerrelated pain should be restricted to experienced physicians to avoid inadvertent over or under dosing.(5) When converting to methadone, dose reduction should be considered.(16) See Appendix B for further methadone information. Tramadol Information (See Appendix C): · · Is a synthetic opioid with analgesia provided via a weak OP3 (mu) receptor effect, and via inhibition of serotonin and noradrenaline reuptake.(31) Appears to provide neuropathic pain benefit.(28,31,36) See Appendix C for more tramadol information Sufentanil Information (See Appendix D): · · · · · Sufentanil is 5 to 10 times more potent than fentanyl.(1) Injectable sufentanil (like fentanyl) is readily absorbed through the mucous membranes.(1) Its early onset of action of about 5 to 10 minutes, when used sublingually, makes it ideal for incident pain control. It provides a peak analgesic effect of 15 to 30 minutes, duration of the analgesic effect of 30 to 40 minutes. Use for incident pain control, dosing 10 to 15 minutes prior to the painful event.(1) Patients need to be able to hold the solution in their mouth for 2 minutes to have transmucosal absorption occur. If swallowed onset of action will be delayed due to slower gastrointestinal absorption rate.(1) Initial dose titration with sufentanil should be approached cautiously in opioid naïve patients or for patients on low doses of opioids, as the dose of 6.25 mcg provides a wide range of approximate dose equivalency of 6.25 to 20 mg of oral morphine.(32,33,34) Many patients tolerate an initial dose of 12.5 mcg. If it is felt that Document1 Page 131 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · sufentanil may be too potent to use for patient taking low doses of opioids fentanyl could be alternatively considered.(1) See Appendix D for use of sufentanil in NH incident pain protocol Recommendation 7 · · · · · · · Routes of Administration of Opioids Patients in the last days and weeks of life often require more than one route of administration.(16) Repeated intramuscular administration of opioids is excessively noxious to palliative care patients and should be avoided.(14, 1618) The duration of action of most drugs is approximately equal to the halflife. Effective duration of action may be shortened in the younger patient and more prolonged in the elderly.(1) The oral route is the preferred route in most palliative care settings.(1, 7, 13, 16, 23) Maximal analgesia is reached at 1.5 to 2 hours for IR preparations,(1) 3 to 4 hours for SR preparations and for methadone.(2) The rectal route has more rapid absorption, within about 10 minutes, and a similar pattern of duration when compared to the oral route. It is not reliable secondary to the amount and consistency of stool in the rectum.(2, 7, 23) o The oral to rectal relative potency is 1:1.(14, 17) o The rectal route should be avoided in patients with rectal or anal lesions(7, 23) or who are neutropenic or thrombocytopenic.(17) o Opioids can be placed in colostomies if the flow of effluent is slow enough to allow absorption.(17) Parenteral routes: o Subcutaneous and intramuscular routes, have an absorption rate of 10 to 15 minutes. o Intravenous injection provides an early immediate peak serum level, while effective analgesia can be delayed for up to 17 minutes due to a delay in drug passing across the blood brain barrier.(1) o Maximum effect is reached quicker than oral. o S.C. starts to lose potency at 45 to 90 minutes, intramuscular medications at 30 to 60 minutes and intravenous medications by 20 minutes.(2) o Use a S.C. butterfly needle for intermittent subcutaneous injections. o Indications for use are: inability to swallow, nausea and/or vomiting, gastrointestinal obstruction or impaired absorption and uncontrolled pain where rapid titration is necessary. o Continuous subcutaneous infusions have been shown to be superior to continuous I.V. infusions in the palliative care setting.(1,23) especially if the q4h dose of an opioid is too large to give on an ongoing basis or the opioid being used has a very short duration of action (fentanyl or sufentanil).(1) When high doses of intravenous morphine are needed, use only preservativefree formulations.(17) The transdermal route is effective but should not be used in patients with advanced cachexia, some elderly, and debilitated patients as they may not absorb the medication adequately or consistently.(13, 21) It is also not a Document1 Page 132 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · recommended route in those with acute or rapidly changing pain and the opioid naïve.(13) The buccal route has a quick absorption rate (10 minutes).(2, 17) Use of concentrated forms of opioids (morphine 20 to 50 mg per mL or hydromorphone 10 to 50 mg per mL) is recommended.(1) The volume of drug dose must be kept at or below 0.5 mL to avoid swallowing or prevent choking.(1, 13) Bioavailability of sublingually administered morphine or hydromorphone will be higher than the same dose given orally, as less drug is initially metabolized due to a first pass effect of the liver.(1) Epidural and intrathecal administration is used in difficult or refractory pain situations.(1) Both these routes require the use of preservative free formulations.(17) Intrathecal injection delivers the drug directly into the cerebral spinal fluid.(1) Topical opioids have been used in managing pain of superficial decubitus or malignant skin ulcers. Morphine can be mixed with Intrasite gel for the treatment of ulcers for direct application.(1, 13, 14) Recommendation 8 · · · · · · Adverse Effects of Opioids Constipation is the only undesirable adverse effect where tolerance does not develop.(1, 8, 9, 12) Ensure a bowel protocol is initiated. See Northern Health Hospice Palliative Care Symptom Guidelines on Constipation for guidance on a suitable bowel regime. Nausea/vomiting – usually mild and rarely persistent,(1, 9, 23) tolerance develops rapidly.(7, 12) Antiemetics can generally be discontinued in a few days when tolerance develops.(8, 17) See Northern Health Hospice Palliative Care Symptom Guidelines on Nausea and Vomiting for guidance in choosing an antiemetic. Sedation – often transient, especially when opioid initiated or increasing doses.(14, 17) Will generally be relieved in 2 to 4 days.(1, 79, 12, 16, 23) Persistent opioid induced sedation is usually best treated by reducing the dosage and increasing the frequency of administration – this decreases peak concentrations while maintaining the same total dose.(8, 17) The use of psychostimulants may be beneficial.(8, 12, 14, 16, 17) Delirium/restlessness may be seen both upon initiation of opioids (frequently in the elderly)(1, 12) and may occur during ongoing opioid therapy when metabolite accumulation occurs.(1, 12, 25) For treatment of true delirium see Northern Health Hospice Palliative Care Symptom Guidelines on Delirium / Restlessness. Urinary retention occurs secondary to increased tone of the bladder sphincter and inattention to the stimulus for bladder emptying. This will generally decrease within one week.(9) Rarely will a patient need to be catheterized.(1, 9, 14) Urinary retention occurs more frequently in men with prostatic hypertrophy, patients with pelvic tumours, or bladder outlet obstruction.(17) Pruritis occurs secondary to the histamine release in drugs like morphine.(7, 16) Patients may need an antihistamine or opioid rotation, if severe.(1, 9, 16, 17) Document1 Page 133 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · Xerostomia (dry mouth) is a common effect of morphine. Good mouth care and frequent sips are effective for most patients. For difficult cases pilocarpine 2% eye drops or 5 mg tablets by mouth three times per day have been suggested.(1) Syncope (dizziness) occurs secondary to orthostatic hypotension caused by venous pooling following histamine release.(1, 9) Patients prone to this effect should be instructed to change positions slowly when moving from lying to sitting or standing.(1) Myoclonus (spontaneous jerking movements) can occur with any dose and route of opioids.(1, 17) Myoclonus may precede the onset of opioidinduced neurotoxicity.(1) See Northern Health Hospice Palliative Care Symptom Guidelines on Myoclonus/Seizures for guidance with this symptom. Opioidinduced neurotoxicity (OIN) includes symptoms such as: hyperalgesia (heightened sensitivity to the existing pain), allodynia (a normally nonnoxious stimuli resulting in a painful sensation), agitation/delirium with hallucinations and possibly seizures.(1, 9, 12) It is due to the accumulation of toxic metabolites and impaired renal function, dehydration and electrolyte imbalances contribute to this condition.(1, 9, 21) OIN occurs more frequently with high dose parenteral administration of morphine(12) and has been observed in cases using high dose hydromorphone.(1) OIN occurs more common in the frail elderly.(9) Grand mal seizure associated with highdose parenteral opioid infusions have been reported and may be due to preservatives in the solution. Preservative free solutions should be used when administering highdose infusions.(16) Opioid rotation should be considered.(1, 21) Respiratory depression occurs rarely in patients receiving opioids regularly as tolerance to the respiratory depressant effect develops rapidly.(1, 79, 14, 16, 17) Opioids should not be withheld for fear of respiratory depression in this group.(17) The risk of respiratory depression is greater in patients with respiratory impairment (pneumonia, those with CO2 retention or chronic obstructive pulmonary disease), and when opioids are used in opioidnaïve patients, or are too rapidly titrated.(1, 9, 17) Recommendation 9 · · · · Opioid Titration When starting an opioid, use immediate release (IR) until dose is stabilized. Alternatively, when pain is mild or moderate, some clinicians may choose to start with an oral controlledrelease (CR) formulation, with an IR form available for breakthrough pain.(13) In opioid naïve patients start with 2.5 to 5 mg of morphine po or 0.5 to 1 mg of hydromorphone po q4h with breakthrough medication ordered at 1.25 to 2.5 mg of morphine po or 0.25 to 0.5 mg hydromorphone po q1h prn. Analgesic effectiveness can be reassessed after 24 hours as it takes five half lives to reach a steady state (5 x 4 hrs = 20 hrs). Total all the regular and breakthrough opioid used in the last 24 hours to get the total daily dose (TDD). Document1 Page 134 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · · · · · Divide this amount by the number of doses for the next 24 hours (normally 6=q4h) and give this dose regularly q4h with 10% of the TDD given q1h p.r.n. as a breakthrough/rescue dose (BTD) for breakthrough/rescue pain.(2) Dose adjustments should not be made more frequently than every 24 hours.(2) Also assess for end of dose pain, and the presence of incident pain, which may require further titration. Use IR opioid formulations for breakthrough doses (BTD)(13) and remember to increase the breakthrough dose proportionately when the regular dose is increased.(2) When full pain relief is achieved, yet adverse effects have developed, employ a dose reduction to try and maintain adequate pain control with diminished adverse effects.(2) Doubling the nightime dose will avoid wakening the patient in the early morning for a scheduled q4h dose, however, night loading doses should be considered only for patients with good pain control.(2,22) The use of sustained release opioids appears to be a better dosing strategy, as shown in a study with SR morphine.(26) When good pain control is achieved with a stable dose with an immediate release formulation, consider use of a long acting product to improve compliance.(2) When the patient is on sustained release opioids or fentanyl patches it is usual to titrate the dose every 48 and 72 hours respectively.(2) If fentanyl is used, total the amount of breakthrough opioid analgesic given in the last 24 hours and convert that amount to an additional equivalent size fentanyl patch. If titration is done frequently switch to a short acting preparation. If pain is rapidly escalating or pain is requiring frequent titration use short acting opioids q4h until pain is controlled and opioid needs are stabilized. Consider development of tolerance (which may require opioid rotation) or reassessment for a new or progressive medical problem. When patients are elderly or frail, titrate over a number of days rather than rapidly over 1 to 2 days.(2, 9) For severe pain the rate of titration may need to be more aggressive – see recommendation 14 (14) Recommendation 10 · · · Use of Long Acting or Sustained Release Opioids Although there are a variety of approaches, these medications are usually used for stable (well controlled) pain only.(1,21,23) Sustained release formulations should not be used to manage uncontrolled pain. Consider a switch to immediate release formulations that provide an improved titration response time. Reevaluate pain control prior to restarting the sustained release formulation.(1, 17, 23) Drugs available in long acting formulations include; codeine, oxycodone, morphine, hydromorphone and fentanyl. Methadone is considered a long acting opioid.(1) Document1 Page 135 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · · Before conversion to a long acting opioid, use immediate release preparations to titrate to the appropriate 24 hour dose (TDD).(1, 14, 17) Steady state when using morphine or hydromorphone sustained release is achieved after 48 to 72 hours. Dosage adjustments for these drugs should be made only every 2 or 3 days.(1, 2) Never prescribe sustained release oral formulations more frequently than q8h.(1) Never prescribe sustained release formulations on an as needed basis. SR tablet forms must be swallowed whole. Capsule forms may be opened up and the contents sprinkled onto food or put down a feeding tube but should not be crushed or chewed.(1, 15) When using longacting preparations, always give a shortacting opioid (solution or tablets) using the 10% TDD equivalency q1h p.r.n. for breakthrough pain (e.g., if the patient is on morphine sustained release 60 mg q12h PO give a breakthrough dose of morphine 10 to 15 mg PO q1h p.r.n.).(1, 7, 8, 12, 13, 17) Preferably use the same drug.(1, 14) Fentanyl transdermal patches require changing q72h but some patients may require changing q48h.(1, 21) The full clinical effects of the fentanyl patch will occur between 24 and 48 hours after application; however, this varies greatly between patients. Recommendation 11 · · · Opioid rotation can be performed using the following methods:(1) o Direct substitution – is used with weaker opioids or in severe opioid induced neurotoxicity. The offending opioid is stopped and the new one started. o Gradual substitution – is used when switching between more potent opioids especially when there are already adverse effects or if the patient has anxiety about the new drug. Over the course of a few days the original analgesic is replaced by the new one. Conversions between opioids: o Due to incomplete crosstolerance between opioids use 6680% of the calculated equivalent dose.(2, 14) The dose should only be reduced if the pain was controlled on the previous medication dosage or if there was opioidinduced neuroexcitation pain.(1, 7, 8) The most common reasons opioids are switched are inadequate pain control or an unacceptable level of adverse effects from a specific opioid which limits dose escalation.(1, 13, 14, 23) The need to switch occurs in 10 to 30% of patients on oral morphine.(2) Recommendation 12 · · Opioid Rotation Opioid Withdrawal Rationale for discontinuing an opioid would include patient achieving appropriate pain control by another method, such as radiation therapy, nerve block or epidural.(1, 7, 8, 14) If the patient has been on opioids for only a short time, abrupt discontinuation should not incur withdrawal symptoms.(1) Document1 Page 136 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · If a patient has been on opioids for greater than one week it is suggested to taper the dose by 20 to 30% every 2 to 3 days until discontinued to prevent a withdrawal syndrome.(8) An alternative method is; for the first 2 days, give half of the previous daily dosage. Then reduce the daily dosage by approximately 25% every 2 days, until a daily dosage of 30 mg of morphine has been reached. After 2 more days on 30 mg per day of morphine, discontinue use.(7) Early symptoms include anxiety and restlessness, sweating, rapid short respirations, slight rhinorrhea and lacrimation and dilated reactive pupils. Late symptoms include marked rhinorrhea and lacrimation, tachypnea, tremor, yawning, piloerection, nausea and vomiting, diarrhea, abdominal pain, fever, leucocytosis and diffuse muscle spasms. Prolonged symptoms include irritability, fatigue, bradycardia and decreased body temperature. Withdrawal syndrome can also be precipitated by the use of opioid antagonists like naloxone. In the rare instance where this drug needs to be used, it should be mixed with 10 mL of saline and administered slowly in 1 mL increments to antagonize the respiratory depressant effects without precipitating an acute episode of withdrawal syndrome.(11, 13) Recommendation 13 Treatment: Nonpharmacological Support and encourage appropriate nonpharmalogical strategies such as: · Physical therapies – hot/cold, tens, ultrasound, hydrotherapy, yoga, positioning, immobilization, exercise, stretching, massage, OT, physio, compression stockings, special beds, skin care (36, 39) · Cognitive therapies – pain log/diary, biofeedback, hypnosis, relaxation, meditation, guided imagery, music therapy (36, 39) · Alternative therapies – aroma therapy, reike, therapeutic touch, accupuncture (36. 39) · Other therapies – spiritual support, psychological support, leisure activities (36, 39) These nonpharmacological strategies may provide additional comfort to patients but do not usually replace the need for pharmacological treatment in end of life care. Recommendation 14 Treatment: Pharmacological There are three simple goals for pain management; · A good night’s sleep, · Pain control during the day while at rest and · Pain control when they are active and ambulatory.(1) Where there is no previous history of opioid intake, the starting dose is calculated by assessing the severity of the pain, patient’s age, weight, sex and general physical condition. Document1 Page 137 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition MILD PAIN (Initial Pain Assessment between 1/10 and 4/10): If pain is expected to remain mild for a significant length of time (weeks to months), use nonopioid or weak opioid analgesics. Go slow and go low.(1, 27) · Acetaminophen 325 to 650 mg PO q4h and q1h p.r.n for BTD (maximum 2.4 g to 4 g per day, depending on age and history of liver dysfunction or alcoholism (see recommendation 15).(23) · ASA 325 to 650 mg PO q4h. Use of enteric coated form can minimize GI discomfort. · NonSteroidal Agents (NSAIDs) are indicated for short term use.(28) Cardiovascular risk with these agents are minimized by using the lowest effective dose, for the shortest period of time.(31) Recently, cardiovascular risk has been shown to be less with traditional NSAIDS ibuprofen and naproxen, than with other NSAIDS such as indomethacin and diclofenac.(29) · Codeine may be added in combination with or without ASA or acetaminophen to control pain. Dosing suggestion: 30 to 60 mg PO q4h and q1h PO p.r.n for BTD.(23) Usual maximal dose is 360 to 600 mg per day.(30) If the pain is not well controlled with these medications proceed to next step but only if doses have been taken appropriately (ie. q4h around the clock). MODERATE PAIN (Initial Pain Assessment of 5/10 or 6/10): If pain has progressed, change to stronger opioids. Oxycodone can be used alone or combined with ASA or acetaminophen. For moderate pain, also use single entity opioids such as morphine, hydromorphone, fentanyl or methadone and cancel analgesic orders for mild pain. Increasing doses of opioids combined with acetaminophen runs the risk of giving toxic doses of acetaminophen to the patient.(2, 31) · If opioid naïve, start on morphine 2.5 to 10 mg oral q4h with 10% of total daily dose (TDD) q1h p.r.n.(31) After 24 hours, if more than three breakthrough doses are needed, increase the regular dose – see opioid titration.(1) · If currently on a weak opioid, discontinue it, start morphine PO q4h at the appropriate equianalgesic dose (taking into consideration the partial cross tolerance between opioids) with 10% TDD q1h p.r.n. for breakthrough pain.(1) If more than three breakthrough doses are required over 24 hours, increase the morphine dose (as per above). SEVERE PAIN (Initial Pain Assessment between 7/10 and 10/10): Initial worst pain intensity between 7 and 10 should be considered a pain emergency and requires rapid titration using oral, subcutaneous or intravenous routes.(2, 31) ‘When pain is high, go high and come down quickly’.(1) Use morphine, hydromorphone, or oxycodone. Acute severe pain initially requires parenteral control with a switch to oral or rectal medication once the pain is relieved. If pain is sudden, acute and severe (i.e., fracture, hemorrhage), then both quick response and high doses are necessary. Once relief is obtained, dose can be reduced. The regimen assumes that usual breakthrough dosing has been ineffective. Document1 Page 138 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · Opioid naïve: o Give standard dose of morphine 5 to 10 mg PO(31) or 5 mg S.C. or 2 to 5 mg I.V.(31) STAT and repeat every 20 minutes for S.C. or every 10 minutes for I.V. until pain breaks (significantly lessens).(1) If on an opioid already: o Using the Subcutaneous Route: · Give onehalf of the regular Q4h PO dose by the S.C. route STAT and if necessary, give this again in 20 minutes, until pain breaks. Double stacking (doubling each dose) may be required if the initial dose is very low – usually doubled only 1 to 3 times.(1) · Continue only until pain just starts to break full relief may not yet be achieved but serum levels are still rising and it is important to then stop, observe and reassess the situation. (1) The timeframe goal for relief is less than one hour and usually occurs by second or third dose. (1) When pain is controlled take 2530% of what was required to ‘break’ the pain crisis, and add this to the previous regular dose. (1). o Using the I.V. Route: · If an I.V. bolus is warranted, give 10 to 20 % of the daily IV morphine equivalent. Reassess at 15 minutes.(31) The effectiveness of the analgesic should be reassessed after 15 minutes. If the pain intensity is unchanged the dose of the opioid should be doubled. If the rating has decreased by less than 50 %, the same dose should be repeated. Once the pain intensity has decreased by more than 50% then calculate the total dose of opioid given over 4 hours and consider this dose the “effective”one to be given.(31) Many painful conditions can be readily managed by generalist physicians, nurses and allied staff. Reality is such, however, that some pain problems are complex and require added expertise.”(16) In these cases, refer to the NH HPC Consult team or if unavailable, the BC Palliative Care Consultation Phone Line 18777115757 when pain persists.(2) Recommendation 15 Nonopioids/Adjuvants/Coanalgesics Adjuvant analgesics are medications that have a primary indication other than for pain but provide analgesia in some situations. They are usually used in combination with opioids or other analgesics and may lead to a reduction in the required dose of opioid. Acetaminophen · Particularily useful in mild to moderate somatic pain and can be effective as a co analgesic in mild to moderate visceral pain alone or in combination with opioids. Anectodal evidence suggests it is effective in headache due to increased ICP, bone pain, neuropathic pain or other specific pains, even if opioids have been unhelpful.(36) · Maximum daily dose for short term use in healthy adults is 4000mg .(36) · Maximum daily dose for long term use in healthy adults is 3200mg.(36) Document1 Page 139 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · · Maximum daily dose in the elderly or in clients with liver dysfunction is 2600mg.(36) These daily doses should not be exceeded due to potential liver toxicity and higher doses are not likely to afford any further clinical benefit. Be cautious with dosing of combination products (eg. Tylenol 3, Percocet, cough and cold preps, etc) – regarding total 24 hour acetaminophen totals Safe to use in patients with history of GI bleeds Safe to use in patients on corticosteroids Usual dose 5001000mg four times daily on a regular basis Maximum effects seen within 48 hours NSAIDS (NonSteroidal Antiinflammatory drugs) · May be useful in mild to moderate nociceptive pain alone or in combination with opioids. · It is believed that NSAIDs produce analgesia through a reduction in activation and sensitization of nociceptors caused by inflammatory mediators such as prostaglandins.(36) · Should not be used in patients with moderate preexisting renal impairment – if used in patients with mild renal impairment, monitor creatinine in 57 days and stop if significantly elevated from baseline. The renal impairment is reversible upon discontinuation of the NSAID. (36) · Monitor blood pressure because in some patients NSAIDs can have quite a dramatic effect on blood pressure within a few days (39) · Do not use if on anticoagulants · Use with caution in elderly or patients with a history of gastric or duodenal bleed as the GI bleed risk is higher · Use with extreme caution in patients on corticosteroids as risk of ulceration and GI bleed risk is higher. · Consider use of gastroprotective agent eg. proton pump inhibitor (pantoprazole) · No evidence to suggest that one NSAID is more effective than another; however, if one NSAID is ineffective, it is reasonable to try another.(36) · Cox2 inhibitors (ie.Celecoxib) may provide a greater GI safety profile; however, there is evidence of an increased risk of serious cardiovascular complications.(36) · Usual starting doses (36) : o Diclofenac 25mg po TID (or suppository 50mg pr TID) o Naproxen 250500mg po BID (or suppository 250500mg pr daily) o Ibuprofen 400mg po TID o Celecoxib 200mg po daily · Maximum effect seen within 48 hours Table 2: Adjuvants/Coanalgesics Pain TYPE Drug TREATMENT Bone Corticosteroids dexamethasone Bisphosphonate clodronate Document1 Drug DOSAGE 48mg po/sc/iv daily to BID 1600mg po daily or 1500mg IV q2weeks Page 140 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition pamidronate zoledronic acid Calcitonin Corticosteroids dexamethasone Neuroleptic methotrimeprazine corticosteroids Nerve Compression dexamethasone Antidepressants Nerve Injury Tricyclics (burning, aching, desipramine dysethetic, nortriptyline pin/needles) amitriptyline SSRIs (less effective) Anticonvulsants (shooting, gabapentin lancinating) Raised Intracranial Pressure pregabalin carbamazepine phenytoin valproic acid clonazepam Membrane Stabilizers Mexiletine NMDA Antagonists dextromethorphan PostHerpetic Neuralgia & Post Mastectomy Pain Muscle Spasm Document1 ketamine amantadine methadone Nitrous Oxide Topical Lidocaine/prilocaine cream (EMLA) capsaicin cream (Zostrix) Antidepressants – TCA’s (see above) Anticonvulsants – Gabapentin (see above) baclofen Benzodiaz. lorazepam diazepam 6090 mg IV q4weeks 4mg IV q4 weeks (also see NH HPC symptom guidelines for hypercalcemia) 50 units/day SC (after test dose) (also see NH HPC symptom guidelines for hypercalcemia) 4mg po/sc/iv bidqid 510mg po/sc bid 4mg po/sc/iv bidqid 75200mg daily 75150mg daily 25300mg po qhs 3001200 mg po tid (start at 100mg qhs) 75150mg bid (start with 75mg bid or 50mg tid) 200300mg po qid (start at 100mg tid) 300500mg po daily (start at 100mg po tid) 5001000mg po tid (start at 250mg po qhs) 28mg po daily (start at 0.5mg po qhs) 600900mg po daily (start at 50100mg po tid) 30mg po q4h (up to 1000mg/day) call NH HPC consult team 100mg po bid call NH HPC consult team qid 510mg po tid 12mg sl/sc/iv q4h 510mg po/pr/iv tid Page 141 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 1 suppository pr q68h prn 12.525mg po q624h prn 10mg po q4h prn (Tenesmoid pain) 25mg po qhs 1mg morphine sulphate powder Open Wounds in 1 gm hydrogel bid qid *adapted with permission from: Spring, B. (2007). Vancouver Coastal Health Community Palliative Care Clinical Practice Guidelines, 2627. Bladder or Rectal Spasm B&O suppository chlorpromazine hyoscine amitriptyline Topical Opioid Cream Other adjuvants/coanalgesics: · nerve blocks, epidurals, radiation (36) References Information for recommendation 113 was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews / systematic reviews, clinical trials, case studies and guidelines / protocols using pain and opioid terms in conjunction with palliative / hospice / end of life / dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Black F, Downing GM. Pain Analgesics. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed.Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 189251. 2. Black F, Wilde J, Downing GM. Pain Principles and Titration. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 15988. 3. McLeod BE. ‘Expert’ nurses decisionmaking regarding intravenous patient controlled analgesia (Unpublished Thesis). The University of British Columbia; 2000. 4. McCaffery M, Pasero C. Assessment. In: McCaffery M, Pasero C, editors. Pain: Clinical Manual. 2nd ed. St. Louis: Mosby; 1999. p. 35102. 5. Bruera E, Pereira J, Watanabe S, Belzile M, Kuehn N, Hanson J. Opioid Rotation in Patients with Cancer Pain. A Retrospective Comparison of Dose Ratios between Methadone, Hydromorphone and Morphine. Cancer. 1996 August 15;78(4):8527. 6. Duquette C. Improving function and quality of life for older adults through pain assessment and management. 2002 [cited 2006 November]; Available from: http://www.medscape.com/viewarticle/443993 7. Waller A, Caroline NL. Principles and techniques of pharmacologic management. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA: ButterworthHeinemann; 2000. p. 4158. 8. Pain. In: Yarbro CH, Frogge MH, Goodman M, editors. Cancer Symptom Management. Sudbury, Massachusetts: Jones and Bartlett 2004. p. 837. 9. Gallagher R. Opioid Side Effects and Special Situations. In: Gallagher R, editor. Managing Cancer Pain The Canadian Health Care Professional’s Reference. Toronto, Ontario: Healthcare & Financial Publishing, Rogers Media; 2005. p. 428. 10. Daeninck P, Shadd J. Nonopioid and adjuvant analgesics. In: Gallagher R, editor. Managing Cancer Pain The Canadian Health Care Professional’s Reference. Toronto, Ontario: Healthcare & Financial Publishing, Rogers Media; 2005. p. 4965. 11. Stimmel B. Symptoms of Opioid Withdrawal. Analgesia & Addiction: The Pharmacologic Treatment of Pain. New York: Raven Press 1983. 12. Bruera E, Kim HN. Cancer Pain. Journal of the American Medical Association. 2003 November 12;290(18):2476 9. 13. Gallagher R. Opioid Therapy for Cancer Pain. In: Gallagher R, editor. Managing Cancer Pain The Canadian Health Care Professional’s Reference. Toronto, Ontario: Healthcare & Financial Publishing, Rogers Media; 2005. p. 2941. 14. Hanks G, Cherny NI, Fallon M. Opioid analgesic therapy. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 31641. Document1 Page 142 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 15. Waller A, Caroline NL. Modalities for Pain Control in Cancer. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA; 2000. p. 2340. 16. Fine PG. Principles of effective pain management at the End of Life. [CME] 2006 [cited 2006 November]; Available from: http://www.medscape.com/viewprogram/6079 17. Miaskowski C, Cleary J, Burney R, Coyne P, Finley R, et al. Guideline for the Management of Cancer Pain in Adults and Children. Guideline for the Management of Cancer Pain in Adults and Children, APS Clinical Practice Guidelines Reprinted with permission of the American Pain Society. 3rd ed. Glenview, Il.: American Pain Society; 2005. p. 5877. 18. World Health Organization. WHO’s Pain Relief Ladder. 1986 [cited 2006 November]; Available from: http://www.who.int/cancer/palliative/painladder/en/ 19. Kobierski BL. The 3 “B’s” of symptom control during opioid therapy. In: Joint Northern Health Fraser Valley Cancer Centre Symptom Guidelines Task Group, editor. Dawson Creek, BC; 2006. 20. End of Life/Palliative Education Resource Center Medical College of Wisconsin, Pain and Palliative Care Committees.Analgesic Prescribing Guidelines. Guidelines for Physician Staff Froedtert Hospital, Milwaukee, Wisconsin [cited 2006 November]; Available from: http://www.eperc.mcw.edu/Educational%20Materials/Clinical/Pain AnalGuide.pdf 21. Harlos M, MacDonald L. Managing pain in palliative patients. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual. 2nd ed. New York: Oxford University Press Inc.; 2005. 22. Tayler C, McLeod B. Linking nursing pain assessment, decisionmaking and documentation. Canadian Journal of Oncology Nursing. 2001;11(1):2832. 23. The Alberta Cancer Board PCN. Management of Cancer Pain. In: Pereira J, Otfinowski PB, Hagen N, Bruera E, Fainsinger R, Summers N, editors. The Alberta Palliative Care Resource. 2nd ed. Calgary, Alberta: The Alberta Cancer Board; 2001. p. 835. 24. Mercadante S, Arcuri E. Opioids and renal function. The Journal of Pain. 2004 February;5(1):219. 25. Glare P, Walsh D, Sheehan D. The adverse effects of morphine: a prospective survey of common symptoms during repeated dosing for chronic cancer pain. American Journal of Hospice and Palliative Medicine. 2006;23(3):22935. 26. Reese TJ, Gwilliam B, Davies A. An assessment of the efficacy and tolerability of a “double dose” of normal release morphine sulphate at bedtime Palliative Medicine 2002. 16(6); 50712. 27. Dean M, Harris JD, Regnard C, Hockley J. Using opioids. Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing Ltd; 2006. p. 4952. 28. Federal Drug Administration. Decision memoanalysis and recommendations for agency action COX2 selective and nonselective NSAIDS. April 15, 2005 [cited 2006 November 23]; Available from http://www.fda.gov/cder/drug/infopage/cox2/NSAIDdecisionMemo.pdf 29. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase. A systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. Journal of American Medical Association. 2006 October 14;296(13):163345. 30. Clinical Pharmacology (database online). Codeine monograph. Gold standard. November 23, 2006 cited; Available from: http://cpip.gsm.com 31. Miaskowski C, Cleary J, Burney R, Coyne P, Finley R, et al. Cancer Pain Management. Guideline for the Management of Cancer Pain in Adults and Children, APS Clinical Practice Guidelines Reprinted with permission of the American Pain Society. 3rd ed. Glenview, Il.: American Pain Society; 2005. p. 3948. 32 Kunz K, Thiesen JA, Schroeder ME. Severe episodic pain: management with sublingual sufentanil. Journal of Pain and Symptom Management. 1993 May;8(4):18990. 33 Donelly S, Davis MP, Walsh D, Naughton M. Morpine in cancer pain management: a practical guide. Supportive Care in Cancer. 2002;10(1):1335. 34 Harlso M. Palliative care incident pain and incident dyspnea protocol [Online] 2002 Dec 8 [cited 2007 Jan 9] Available from: URL: http://www.palliative.info/incidentpain.htm 35. Pharmacists Letter / Prescribers Letter. Analgesic Options for Patients with Allergic – Type Opioid Reactions. Volume 22 – Number 220201. Feb 2006. www.pharmacistsletter.com 36. Eddy, B., Geddes, V., Lochbaum, J., Nixon. A., Spring, B., Tanner, M., Tuyp, R., Yearwood, L. Pain Management. In: Vancouver Coastal Health Community Palliative Care Clinical Practice Guidelines. 2007. p.68 37, Spring, B. (2007). Vancouver Coastal Health Community Palliative Care Clinical Practice Guidelines, 2627. 38. Harrigan Consulting. Best Practices for the Nursing Care of the Older Adult. Network of Excellence for Geriatric Services. Northern Health – Clinical Practice Guidelines – End of Life Care – April 2007. 39. Harrigan Consulting. Best Practices for the Nursing Care of the Older Adult. Network of Excellence for Geriatric Services. Northern Health – Clinical Practice Guidelines – Assessment and Management of Persistent Pain – October 2005. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 143 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix A Fentanyl Transdermal Principles A. Indications For Fentanyl Transdermal Use · · · · · Noninvasive alternative to oral medications. Poor absorption of oral opioids. Pain that is stable;(1) pain controlled for at least 48 hours. To provide around the clock opioid treatment(1,2) and improve patient compliance.(3,4) To potentially lower opioid adverse side effects of constipation,(5,6) nausea,(5) and histamine release.(7,8) B. Contraindications To Fentanyl Transdermal Use · · · · Opioid naïve.(1,2,9) Previous opioid dose is less than 45 to 134 mg of oral morphine equivalent per 24 hours.(1) Unstable or poorly controlled pain.(4,5) Acute pain management, e.g. postoperative, or acute pain titration.(1,2) C. Precautions · · · · · · · Elevated temperature may increase fentanyl concentrations.(1,2,10) Monitor. Avoid application site exposure to heat sources such as hot tubs, waterbeds, hot water bottles, etc.(1,2) Cachectic patients, may have reduced subcutaneous fat tissue for reliable drug depot release hence fentanyl pharmacokinetics may be altered.(1,2) Do not cut the reservoir membranecontrolled patch delivery system.(1,2) This patch type, if cut, may affect the rate the drug is released, and risk a toxic skin reaction and overdose.(1,2,11) The newest fentanyl patch matrix system (drugin adhesive) has been cut in successful clinical use although no studies have been completed.(12) Therefore, it is not recommended to cut these patches. Used fentanyl patches may contain enough residual drug to cause serious problems for children, opioidnaïve patients and pets.(1) Ensure they are disposed of properly: fold used patches in half then place in needle disposal container, or place in tamperproof container and return to a community pharmacy, to prevent misuse.(13) Caregivers should wear gloves when handling the patch.(14) Flush skin with water only if patch drug reservoir gel accidentally touches skin, do not use soap or alcohol based sanitizer.(1,2) Document1 Page 144 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · Refer to fentanyl transdermal patch product monographs for complete precaution listing. D. Properties · · · · · · Fentanyl blood concentrations level off between 12 to 24 hours.(3) Most commonly, full clinical effects will occur between 24 and 48 hours after patch application (9) but this can vary greatly between patients. Fentanyl is suited for transdermal delivery because of its low molecular weight, lipid solubility and high potency.(3,9) No pharmacologic dose ceiling, but practical available skin coverage limits dose. No known active metabolites, thus useful for patients with renal impairment.(15) Silicone contact adhesive, alcohol and hydroxyethyl cellulose drug reservoir.(1,2,5) Fentanyl Transdermal Equianalgesic Conversion Chart* Morphine PO (mg per day) 60 134 135 224 225 314 315 404 405494 495 584 585674 675 764 765 854 855 944 945 1034 1035 1124 Hydromorphone PO (mg per day) 12 26 27 44 45 62 63 80 8198 99 116 117 134 135 152 153 170 171 188 189206 207224 Oxycodone PO (mg per day) 4089 90149 150209 210269 270329 330389 390449 450509 510569 570629 630689 690749 Fentanyl Patch (mcg per day) 25 50 75 100 125 150 175 200 225 250 275 300 *The conversions between fentanyl and morphine are taken from the 2004 Compendium of Pharmaceuticals and Specialties.(16) The hydromorphone and oxycodone conversion are based on a morphine to hydromorphone ratio of (5:1) and a morphine to oxycodone ratio of (1.5:1) Approximate Breakthrough Doses Recommended for Fentanyl Transdermal Patch Patch Strength Oral Morphine Oral Hydromorphone Oral Oxycodone Immediate Release(17) Immediate Release(17) Immediate Release 12 mcg / hour 5 mg 1 mg 2.5 to 3.75 mg 25 mcg / hour 10 mg 2 mg 5 to 7.5 mg 50 mcg / hour 20 mg 4 mg 10 to 15 mg 75 mcg / hour 30 mg 6 mg 15 to 25 mg 100mcg / hour 40 mg 8 mg 20 to 30 mg Document1 Page 145 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Conversion Guidelines Between Fentanyl Transdermal Patch and Oral and Subcutaneous Opioids Over First 12 Hours(18) 0 Hour Immediate release oral to TD Patch Apply Patch Give one IR Dose Sustained release to TD Patch Apply Patch Give one SR Dose Subcutaneous to TD Patch Apply Patch Give full S.C. Dose CSCI to TD Patch Apply Patch, 2 /3 CSCI dose for 6 hours, then 1 /3 CSCI dose for 6 Hours 4 Hour One IR Dose 8 Hour 12 Hour One IR Dose 2 /3 S.C. dose 1 /3 S.C. dose Stop S.C. Stop CSCI TD Patch to sustained release oral Remove Patch Full SR dose TD Patch to intermittent S.C. Remove Patch 1 /4 S.C. dose ½ S.C. dose Full S.C. dose TD Patch to CSCI Remove Patch 1 /4 CSCI dose ½ CSCI dose Full CSCI dose **NOTE: Provide prn Breakthrough dose throughout Conversions Abbreviations: TD Transdermal, IR Immediate Release, SR Sustained Release, S.C. Subcutaneous, CSCI Continuous Subcutaneous Infusion, p.r.n. as needed E. Converting To Fentanyl Transdermal Patch · · · · Calculate the total daily dose of current opioid. Convert this into oral equivalent for morphine, hydromorphone or oxycodone. Use Fentanyl Transdermal Equianalgesic Conversion Chart to determine the equivalent dose of transdermal fentanyl. Always provide a breakthrough dose selecting the appropriate dose from the Approximate Breakthrough Doses Recommended for Fentanyl Transdermal Patchchart. Provision of breakthrough doses is important, as the conversion chart is conservative,(19) and approximate. Individualize patient treatment, for in clinical trials, 50% of patients required a dose increase after the initial patch strength application.(3) If breakthrough doses are given S.C. give onehalf the oral dosage. F. Initiation Of Fentanyl Transdermal Patch · · Apply patch to a nonhairy skin area on chest, back, flank or upper arm.(1,2) Note or record placement location to ensure removal in 72 hours time, prior to next dose replacement. During the first twelve hours after the patch has been started, utilize appropriate regular dosing during the transition, AS WELL AS p.r.n. dosing; refer to Conversion Guidelines Between Fentanyl Transdermal Patch and Oral and Subcutaneous Opioids Over First 12 Hours chart. Document1 Page 146 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · Consider applying the first patch at bedtime, as lower pain requirements may occur at night,(20,21,22) permitting peak levels to occur during the day. G. Dose Titration With Fentanyl Transdermal Patch · · · · · · Wait a minimum of three days between dose changes.(15) Total amount of breakthrough doses in prior 24 hours to guide incremental dose increase.(19) Consider a 30 to 50% baseline dose increase,(23) while using the available patch strengths. Thus after a patient was successfully initiated on a 12 mcg per hour patch, consider the following progressive steps: 12 » 25 » 37 » 50 » 75 » 100 » 150 » 200 mcg per hour etc. When less than a full patch dose is desired, a successfully used method is to apply an occlusive dressing (such as TEGADERM) onto the skin to block the appropriate surface area portion of the patch exposed to the skin., e.g. half the patch on the dressing and half on the skin.(24) Rarely do patients require patches to be replaced more frequently than every three days. Early wearing off of the patch’s effectiveness (end of dose failure) can indicate underdosing and the need for the patch dose strength to be increased. Provide and appropriately adjust for a new p.r.n. breakthrough dose.(4,9) H. Discontinuation Of Fentanyl Transdermal Patch · · Upon removal of the patch, the depot of medication within the subcutaneous skin tissue and drug elimination will diminish by 50% within seventeen hours of removal.(3) Refer to Conversion Guidelines Between Fentanyl Transdermal Patch and Oral and Subcutaneous Opioids Over First 12 Hours, when discontinuing patch and initiating sustained release oral therapy, intermittent S.C. or CSCI therapy. I. Disposal of Fentanyl Transdermal Patch · Used fentanyl patches may contain enough residual drug to cause serious problems for children, opioidnaïve patients and pets.(1) Ensure they are disposed of properly: fold used patches in half then place in needle disposal container, or place in tamperproof container and return to a community pharmacy, to prevent misuse.(13) References 1) Duragesic product monograph [Online]. May 29 [cited 2006 Nov 23];Available from: URL: http://www.janssenortho . com/JOI/en/ 2) RANFentanyl Transdermal system product monograph 2006 Aug 18 Ranbaxy Pharmaceuticals Canada Inc Mississauga Ontario. 3) Muijsers RBR, Wagstaff AJ. Transdermal Fentanyl an updated review of its pharmacological properties and therapeutic efficacy in chronic cancer pain control. Drugs 2001; 61(15):2289307. Document1 Page 147 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 4) Carver AC, and Foley KM. Palliative care symptom assessment and management. Neurologic Clinics 2001 Nov; 19(4). 5) Grond S, Radbruch L, Lehmann K. Clinical pharmacokinetics of transdermal opioids. 2000 Jan; 38(1):5989. 6) Radbruch L Sabatowski R, Loick G, Kulbe C, Kasper M, Grond S et al. Constipation and the use of laxatives: a comparison between transdermal fentanyl and oral morphine. Palliative Medicine 2000;14:1119. 7) Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H et al. Strategies to manage the adverse effects of oral morphine: a evidencebased report Expert working group of the EAPC. Journal of Clinical Oncology 2001 May1;19(9):254254. 8) Jovey RD, editor. Managing Pain the Canadian Healthcare Professional’s Reference. Toronto Ontario: Rogers Media Publishing; 2002. 9) Davis M, Glare P, Hardy J. Opioids in cancer pain. Oxford (U.K.): Oxford University Press; 2005 p.1623. 10) Ashburn MA, Ogden LL, Zhang J, Love G, Basta SV. The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat. The journal of pain 2003 Aug;4(6)2917. 11) Belanger D. Can you give a patient a partial dose from a transdermal patch? Medication Forum Pharmacy Practice 1998 Sep. 12) Cutting fentanyl matrix patches. Newsletter.[Online] 2005 May/June [cited 2006 Nov 23] Available from: URL: Error! Hyperlink reference not valid. 13) College of Pharmacists of British Columbia Fentanyl/Duragesic patch Alert Bulletin May 2005 [Online] Available from: URL: http://www.bcpharmacists.org/new/pdf/fentanyl_10.pdf [cited 2006 Nov 24] 14) GardnerNix J. Caregiver toxicity from Transdermal Fentanyl Journal of pain and symptom management 2001 Jun;21(6):4478. 15) Dean M. Opioids in renal failure and dialysis patients. Journal of pain and symptom management 2004 Nov;28(5):497504. 16) Compendium of pharmaceuticals and specialties 39th Ed. Toronto Ontario: Canadian Pharmacists Association; 2004. 17) Palliative Care Pain and Symptom Management Guidelines and Protocols. Interior Health; June 2004. 18) Néron A. ed. Pharmacy specialty group on palliative care. Care Beyond Cure A Pharmacotherapeutic Guide to Palliative Care. Montréal (Canada): Canadian Society of Hospital Pharmacists; 2000. p.18. 19) Woodroffe MA, Hays H. Fentanyl transdermal system. Canadian Family Physician 1997;43:26872. 20) Wiffen, PJ; Edwards, JE; Barden, J; McQuay, HJM. Oral morphine for cancer pain [Review] Cochrane database of systemic reviews 2004 Oct 12; 1 21) Mercadante S, Radbruch L, Caraceini A, Cherny N, Kaasa S, Nauck F, Ripamonti C, De Conno F. Episodic (breakthrough) pain consensus conference of an expert working group of the European Association for Palliative Care. Cancer 2002 Feb 1;94(3):8329. 22) Fine PG, and Busch MA. Characterization of breakthrough pain by hospice patients and their caregivers. Journal of Pain and Symptom Management 1998 Sep;16 (3):179–183. 23) Black F, Downing GM. Pain Analgesics. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 189251. 24) Fentanyl transdermal patch safety concern. Drug and therapeutics newsletter. [Online]. 2005 Dec 12(4); [cited 2006 Nov 24] Available from: URL: http://www.vhpharmsci.com/Newsletters/2005NEWS/Dec05_news.pdf Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 148 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix B Methadone Principles A. Characteristics Of all the medications used in Palliative Medicine, methadone should command the greatest respect. Only physicians experienced in methadone use should initiate methadone treatment.(16) Its use is highly individualized, and demands finesse, skill and knowledge for use in carefully supervised settings. Methadone is a potent analgesic utilizing OP3 (mu)(7) and OP1 (delta)(7) opioid receptor agonist with Nmethyldaspartate (NMDA)(2,4) receptor antagonist actions. It is used for neuropathic pain management in clinical practice;(810) controlled studies have yet to confirm its role in neuropathic pain of malignant origins.(11,12) Its prolonged and variable halflife makes titration difficult.(8,1315) Liver metabolism produces no active metabolites,(1,2,4,6,11,14,1620) making it useful in renal impairment and for use in dialysis patients.(2,4,12,16,19) Excretion occurs via feces and urine.(14,16, 21,22) The potency of methadone has been underestimated in the past, and controversy exists over the equianalgesic dose.(21) The higher the dose of the previous opioid, the more powerful methadone appears.(1,4,23) Older equianalgesic tables based equivalency on single dose studies (suggested a 1 mg methadone = 1 mg morphine ratio), and not longterm dosing.(3,14,16,21,24) Pain control conversions have occurred where the dose of methadone has been as little as 1/240th of the previous high dose of morphine.(17) Methadone’s effect on the NMDA receptor may be part of the reason why the conversion ratio changes in chronic use.(8) Antagonism of NMDA may produce a reversal of tolerance,(1,8,13,21) reduce the tolerance of morphine, and improve pain control.(8) A low incidence of dose escalation has been shown in chronic treatment.(2,11,20) Side Effects: The side effects of nausea,(12,16) constipation,(3,4,6,12,16,25) and confusion(6,16)are often less than for other opioids. Additional side effects include sedation, dizziness, pruritus, sweating, vomiting, risk of urinary retention, dry mouth, and insomnia.(2,3,12,14,22) Several reports have been published of prolonged QTc (corrected QT interval), torsades de pointes (TdP) (a type of paroxysmal ventricular tachycardia) and syncope in patients taking high doses of methadone, greater than 200 mg per 24 hours.(6,22,2628) Prolonged QT interval is associated with TdP, ventricular fibrillation and sudden cardiac death.(1,9,22,2931) Palliative care patients are at risk in the presence of heart disease,(22,29) abnormal liver function, low potassium and calcium, and while using selected drugs.(7,29,32,33) Refer to Table 2 for a list of drugs associated with prolonged QT interval and TdP. Document1 Page 149 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Suppositories can be pharmaceutically compounded for rectal route use.(3,5,14,23) Commercially, methadone is available in oral formulations of tablets of 1 mg, 5 mg. 10 mg, 25 mg and standard strengths of liquid 1 mg per mL and 10 mg per mL. Its bitter taste can be made more palatable by adding to liquids such as fruit juice(55) or chocolate milk.(5) Applesauce or a candy taken after a dose may alleviate the bitterness.(14) Methadone has been used intravenously(7,8) subcutaneously,(35,36) and intramuscularly,(14) although obtaining this form of the drug requires importation via Health Canada’s Special Access Program ( http://www.hcsc.gc.ca/dhpmps/acces/drugsdrogues/index_e.ht mL). B. Properties · · · · · · · · · · · · · OP3 (Mu)(2,7,37) agonist, OP1 (delta)(7,37) and OP2 (kappa)(7,37) agonist and NMDA receptor(2,4) antagonist. Serotonin and norephinephrine uptake inhibitor.(2,25) High bioavailablity 80% orally,(14,8,12,16,23) 34% when liquid given sublingually.(25,38) Rapid onset of pain relief due to good absorption within 30 minutes,(5,14,2123) peak levels occur 2 to 4 hours after ingestion.(14) Large initial volume of distribution.(8,16,23) Has a 2 to 3 hour initial phase,(4,18,21) then a 15 to 60 hour elimination phase.(2,18,39) Long half life varies from 15 to 60 hours,(25) up to 120 hours in cancer patients.(21,22) Dosing frequency of q6h, q8h or q12h(13) does not necessarily reflect half life. Metabolized in liver, mainly by CYP3A4 and to a lesser extent by CYP1A2 and CYP2D6.(2,16,21) Other minor enzymes involved are CYP2B6, CYP2C9, CYP2C19 and(25) Inexpensive(3,4,12,16,18,20,24) and easily manufactured synthetic opioid.(34) Effects can be reversed with use of naloxone.(4,7,10,14,56) The relative analgesic potency ratio of oral to parenteral methadone is 2:1.(7,16,25) The relative conversion from oral to rectal is 1:1,(16,25) although some clinical experience suggests that 50 % greater rectal doses may be required when switching from oral dosing.(40) C. Indications · · · · · Opioid neurotoxicity.(4,11,14,16,17) Opioid tolerance.(2,11,14,16) Uncontrolled neuropathic pain.(1,4,17,21) True morphine allergy. Treatment of cancer pain in patients on chronic methadone maintenance therapy.(13) Document1 Page 150 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition D. Disadvantages (Challenges) · · · · · · · · · · · · · · · Wide, unpredictable variable interpatient pharmacokinetics.(1,3,4,10,14,16,18,21,2325) Poorly defined equinanalgesic potency.(1,9,12,23) Potency ratio changes with higher doses.(1,4,23) Deposition in tissues can occur as a result of the dissociation between halflife and analgesic duration and poses the risk of delayed toxicity.(5,6,23,41) Risk of respiratory depression, greatest at the start of therapy.(3,13,25) Rotation best done as an inpatient, particularly when rapid opioid rotation desired.(3,4,15,23,42) Successful titration in the community has been done with daily health care contact (phone call) and frequent and regular assessment by the family until titration is complete.(23) Time to steady state is 48 to 240 hours,(6) and requires ongoing monitoring for up to 10 days after dose change to follow for drowsiness, risk of respiratory depression. Several drug interactions.(4,18) (see Table 1) Autoinduction of metabolism by CYP3A4 increases clearance in chronic dosing.(2,16) Requires a special license to prescribe for pain.(2,3,5,15,43) Requires skilled prescriber.(41) No randomized controlled trials to support its role in cancer(15,34) and noncancer (44) pain management. No comparative studies regarding the effectiveness of the different methadone switching methods.(1,4,5,9,11,34) No comparative studies to provide an optimum titration strategy.(34,45,46) Choice of breakthrough (rescue) drug not established in literature and clinical practice.(14) Requires safeguards for use by patient only, to avoid accidental ingestion, as a 10 mg dose can be fatal for a child, or 40 mg for a nontolerant adult.(14) Store in a childproof container within a locked box.(14,15) E. Contraindications · · · · · Methadone allergy.(16) Concurrent monoamine oxidase inhibitor therapy.(16) Concurrent pentazocine, nalbuphine, butorphanol – may precipitate withdrawal symptoms.(14) A setting of respiratory depression.(16,22) Relative Contraindication: prolonged QTc defined as greater than 450 milliseconds for males and greater than 470 milliseconds for females.(47) Particular risk occurs with an uncorrected QT greater than 500 milliseconds.(47) F. Practice · Consultation with the Hospice Palliative Consultation Team/Physician/Pharmacist is recommended because of the complexities of methadone use. Document1 Page 151 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · For a physician to obtain the necessary prescribing or inpatient reordering authority, contact the College of Physicians and Surgeons 6047337758 extension 2246 or 18004613008.(5) QTc should be measured before embarking on methadone treatment and when the dose approaches 200 mg per 24 hours.(6,15,47) Risk of torsades de pointes grows as QTc increases, particularly greater than 500 milliseconds.(47) Whenever a drug increases the QTc by 30 to 60 milliseconds in an individual, this should raise a concern.(30,33,47) When possible, electrocardiograms should be performed during peak drug concentration. G. Dosages Various methods are used to initiate methadone in patients. Suggested methods follow: 1. Opioid Naïve Patients: (Twycross)(48) “start low go slow” · · · · · · · · Start with 5 mg q4h p.r.n. On day 4 summate doses and calculate q8h. 10% Total Daily Dose (TDD) for rescue. Alternate Regimen: (palliativedrugs.com newsletter Feb 2001).(49) Start methadone 5 mg q12h and 5 mg q3h p.r.n. If pain control inadequate increase to 10 mg q12h after 1 to 2 days; preference is not to change regular dose for 1 week. Can titrate up by 1/3 to 1/2 once a week. With higher regular doses increase the rescue dose to 1/8. 2. Dosing Guide For Opioid Tolerant Patients Daily oral Conversion ratio Morphine equivalents(1) Morphine to Methadone(1) <100 mg 101 – 300 mg 301 – 600 mg 601 – 800 mg 801 – 1000 mg >1000 mg 3:1 5:1 10:1 12:1 15:1 20:1 Due to incomplete crosstolerance reduce initial calculated dose by 50% Document1 Page 152 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 3. Schedule (modified after Bruera, E and Newman C)(50) Calculate methadone total daily dose equivalent according to the table above. Day 1: reduce original analgesic by 1/3 add 1/3 as calculated methadone dose use original analgesic for rescue Day 2: reduce original analgesic by 2/3 add 2/3 as calculated methadone dose use original analgesic for rescue Day 3: give total dose as methadone use methadone for rescue – 10% TDD q3h p.r.n. · · · · · Use of methadone for breakthrough dosing may be preferred as patients on methadone may be at least partially refractory to the effects of other opioids. Some clinicians recommend only starting methadone for breakthrough doses once a regular methadone dose is established.(3) Patients 65 years and older may have a decreased clearance of methadone.(1) In patients with stable chronic liver disease, no dosage adjustments appear to be necessary.(21,25) Methadone’s halflife may be prolonged in patients with severe cirrhosis.(51) Dosing frequency is normally q8h.(5,52) Intervals of 12 hours may be attempted when patients are stable at q8h dosing.(7) A dosing frequency of every 6 to 12 hours is recommended for pain control in patients previously on once daily methadone maintenance for heroin addiction.(13) Should a patient need to be rotated off methadone, the residual methadone analgesia may directly interfere with the new opioid for days after methadone’s discontinuation due to its long half life.(13) 4. Monitoring · · Monitor for sedation, lethargy, confusion and respiratory depression q6h for 3 to 6 days after initiation or dose change, then daily until at least day 10. Respiratory depression risk reported greatest from day 4 to day 6.(52) Pulse may slow and blood pressure lower in overdoses.(5) Individualized patient dosing and evaluation is the best way to ensure the safe use of methadone.(5,23) H. Drug Interactions: For drug interactions known to occur with methadone, see below. Consult current sources for further and recent drug listings. Document1 Page 153 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1 – Methadone Drug Interactions(14,16,22,53) Drug Effect on Mechanism If Interaction Comments Methadone Level Abacavir Decrease Enzyme Induction Enzyme Early, additive CNS depressant effect Inductionchronic use Common enzyme May increase or decrease pathway Alcohol Decrease Alfentanil Unpredictable Amiodarone Increase Amitriptyline Increase Ammonium Chloride Amprenavir Decrease Ascorbic Acid Decrease Decreased renal reabsorption Antacids Decrease Reduced absorption Barbiturates Decrease Enzyme Induction CYP3A4 & CYP2D6 Reduced clearance Decrease Benzodiazepines Additive euphoria Methadone may also decrease amprenavir Additive toxicity Buprenorphine In high doses that acidify urine Risk of Respiratory depression, sedation Contraindicated, opioid withdrawal risk Bosentan Decrease CYP3A4 Butorphanol Decrease Cannabis Unpredictable Receptor Contraindicated, opioid antagonist withdrawal risk Common enzyme May increase or decrease pathway Carbamazepine Decrease Enzyme Induction Risk of methadone of CYP3A4 withdrawal Chloral Hydrate Report of single fatal additive effects with methadone Cimetidine Increase Ciprofloxacin Increase Document1 CYP1A2& CYP2D6 CYP1A2 & CYP3A4 Page 154 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Clarithromycin Increase CYP3A4 Cocaine Decrease Delavirdine Increase Methadone elimination accelerated CYP2D6 Desipramine Unpredictable Dexamethasone Decrease Dextromethorphan Diazepam Possible increased TCA toxicity, uncertain effect on methadone CYP450 induction CYP450 induction Increase Dihydroergotamine Increase May increase levels of Dextromethorphan CYP3A4 Diltiazem Increase Enzyme inhibition, CYP3A4 CYP3A4 Efavirenz Decrease CYP3A4 Erythromycin Increase CYP3A4 Ethanol (acute use) Increase Fentanyl Unpredictable CYP450 competition or inhibition Common CYP450 pathway Fluconazole Increase CYP3A4 Fluoxetine Increase Fluvoxamine Increase Fusidic acid Decrease Grapefruit Juice Increase CYP2D6 & CYP3A4 CYP1A2 & CYP3A4 Enzyme Induction CYP3A4 CYP3A4 Heroin Decrease Possible additive effects Methadone free fraction lessened Imipramine Possible increased TCA toxicity, uncertain effect on methadone Isoniazid Increase CYP 1A2 Itraconazole Increase CYP3A4 Ketoconazole Increase CYP3A4 Meclizine Unpredictable Increased sedative effects if abused Meperidine Unpredictable Possible opioid additive effects Document1 Page 155 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Methylphenidate Unpredictable Possible CYP450 enzyme inhibition Increase CYP3A4 Proposed in literature, but unverified Metronidazole Increase Moclobemide Increase CYP2D6, CYP1A2 Nalbuphine Decrease Naloxone Decrease Receptor Contraindicated, opioid displacement withdrawal risk Enzyme Induction Naltrexone Decrease Receptor displacement Nifedipine Contraindicated, opioid withdrawal risk Nifedipine increase proposed Nelfinavir Decrease CYP3A4 Enzyme Induction Nevirapine Decrease CYP450 Enzyme Induction Methadone withdrawal cases Octreotide Decrease Omeprazole Increase Methadone absorption Occurred in animal studies Paroxetine Increase CYP2D6 Pentazocine Decrease Can cause opioid withdrawal Pentobarbital Decrease Receptor antagonist CYP340 enzyme induction Phenobarbital Decrease CYP340 enzyme induction Can cause sharp decrease in methadone Phenytoin Decrease Primidone Decrease Enzyme Induction, CYP3A4,CYP2B6 Enzyme Induction Promethazine Unpredictable Propafenone Increase CYP2D6 Propoxyphene Increase CYP3A4 Quinidine Increase CYP2D6 Rifampin Risperidone Decrease Decrease Enzyme Induction Cases of severe withdrawal reported Mechanism unclear Ritonavir Decrease CYP3A4 Sertraline Increase CYP2D6 enzyme Document1 Possible increased sedation or methadone effects Page 156 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition inhibition Sodium Bicarbonate Increase Decreased urinary excretion of methadone Spironolactone Decrease Enzyme Induction, CYP3A4 Stavudine Unpredictable St. John’s Wort Tramadol Decrease Trimipramine Unpredictable Verapamil Increase CYP3A4 Zafirlukast Increase CYP3A4 Zidovudine Unpredictable Zidovudine concentration increase Zopiclone Unpredictable Potential interaction, additive CNS depression CYP3A4 Decreased stavudine concentration Can cause significant decrease Potential withdrawal risk. Avoid concurrent use with methadone Possible increased TCA toxicity, uncertain effect on methadone Table 2 – Drugs that may predispose to QT interval prolongation or torsades de pointes (29,30,33,54) adenosoine amantadine amiodarone amitriptyline azithromycin bupropion cetirizine chloral hydrate chloroquine chlorpheniramine chlorpromazine ciprofloxacin citalopram clarithromycin clemastine clindamycin clomipramine clozapine cocaine cotrimoxazole cyproheptadine desipramine diltiazem dimenhyDRINATE diphenhydrAMINE Document1 domperidone doxepin droperidol enflurane erythromycin famotidine fentanyl fexofenadine flecainide fluconazole fluoxetine foscarnet fosphenytoin gatifloxacin glyburide granisetron haloperidol halothane hydroxyzine ibutilide imipramine indapamide isoflurane isoproterenol ketamine lithium losartan maprotiline mefloquine meperidine methadone mexiletine moxifloxacin naratriptan nicardipine nortriptyline octreotide ofloxacin olanzepine ondansetron paroxetine pentamidine pentobarbital imozide probucol procainamide prochlorperazine promethazine propafenone propofol quinine risperidone rizatriptan salbutamol salmeterol sertraline sevoflurane sildenafil sotalol spiramycin sufentanil sumatriptan tacrolimus tamoxifen telithromycin terfenadine thiopental thioridazine tizanidine trazodone triamterene trifluoperazine vasopressin venlafaxine verapamil Page 157 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition disopyramide dolasetron ketoconazole levofloxacin quetiapine quinidine voriconazole zolmitriptan The potential each of these drugs has to predispose to QT prolongation and torsades de pointes varies, but the extent is specific to the drug. Concomitant drug use in susceptible patients should be evaluated alongside other medical risk factors. Consult current sources for further and recent drug listings. References 1) Gazelle G, Fine PG. Fast fact and concept #075 Methadone for Pain. EndofLife physician resource center [Online]. Sep 2002 [cited 2005 Nov 12]; Available from: URL: http://www.eperc.mcw.edu 2) Lister D. The case for methadone an alternative to other opioids in the management of severe pain. Pharmacy Practice 2002 Sep;18(9):5964. 3) Taube AW. Methadone: what is its role in cancer pain control? The Canadian Journal of CME 2003 Sep;909 4) Bruera E, Sweeney C. Methadone use in cancer patients with pain: a review. Journal of Palliative Medicine 2002; 5(1):12738. 5) College of Physicians and Surgeons of BC. Recommendations for the use of methadone for pain; 2005 March. 6) Black F, Downing GM. Pain – Analgesics. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 189251. 7) Methadone Clinical Pharmacology [Online]. 2006 Gold Standard [cited 2006 June 30];Available from: URL:http://www.clinicalpharmacology.com/Default.asp 8) Fitzgibbon D, Ready LB. Intravenous highdose methadone administered by patient controlled analgesia and continuous infusion for the treatment of cancer pain refractory to highdose morphine. Pain 1997;(73): 25961. 9) Gan B, Almahrezi A, Schreier G. Methadone in the treatment of neuropathic pain. Pain Research and Management 2003; 8(3):14954. 10) Oneschuk D, Bruera E. Respiratory depression during methadone rotation in a patient with advanced cancer. Journal of Palliative Care 2000;16(2):504. 11) Moryl N, SantiagoPalma J, Kornick C, Derby S, Fischer D, Payne R et al. Pitfalls of opioid rotation: substituting another opioid for methadone in patients with cancer pain. Pain 2002;96:3258. 12) Mercadante S, Casuccio A, Fulfaro F, Groff L, Boffi R, Villari P et al. Switching from morphine to methadone to improve analgesia and tolerability in cancer patients: a prospective study. Journal of Clinical Oncology 2001;19(11):2898904. 13) Manfredi PL, Gonzales GR, Cheville AL, Kornick C, Payne R. Methadone analgesia in cancer patients on chronic methadone maintenance therapy. Journal of Pain and Symptom Management 2001 Feb;21(2):16974. 14) Brands, J Janecek E. Methadone maintenance: a pharmacist’s guide to treatment. Centre for Addiction and Mental Health, Toronto Ontario;2000. 15) College of Physicians and Surgeons of Ontario. Methadone for pain guidelines 2004 Nov [cited 2005 Dec 17] Available from: URL: http://www. cpso.on.ca/publications/publications.htm 16) Davis MP, Walsh C. Methadone for relief of cancer pain: a review of pharmacokinetics, pharmacodynamics, drug interactions and protocols for administration. Supportive Care in Cancer 2001;9:7383. 17) Downing, MP. Opioid rotation, neurotoxicity and paradoxical pain. Victoria Hospice Society palliative care medical intensive course November 2004 p. 16. 18) von Gunten CF. Fast fact and concept #086:Methadone:starting dose information 2003 Mar [cited 2005 Jan 3]; Available from:URL: http://eperc.mcw.edu/fastFactff_86.htm 19) Dean, M. Opioids in renal failure and dialysis patients. Journal of Pain and Symptom Management 2004 Nov; 28(5):497504. 20) Ripamonti C, Bianchi M, Bruera E. Methadone: an orphan drug? Letter to the editor. Journal of Palliative Medicine 2004;7(1):734. 21) LaysonWolf C, Goode JV, Small RE. Clinical Use of Methadone. Journal of Pain and Palliative care Pharmacology 2002;16(1);2959. 22) Methadone monograph [Online]. 2005 [cited 2005 Jan 3]; Available from URL: http://www.clinicalpharmacology.com/ Default.asp 23) Hagen NA, Wasylenki E. Methadone:outpatient titration and monitoring strategies in cancer patients. Journal of Pain and Symptom Management 1999;18(5):36975. 24) Lawlor P, Turner K, Hanson J, Bruera E. Dose ratio between morphine and methadone in patients with cancer pain. Cancer 1998;82(6):116773. Document1 Page 158 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 25) Davis M. Methadone In: Davis M, Glare P, Hardy J. editors. Opioids in cancer pain. Oxford (U.K.): Oxford University Press; 2005 p.173198. 26) Walker PW, Klein D, Kasza L. High dose methadone and ventricular arrhythmias: a report of three cases. Pain 2003;103:3214. 27) Krantz MJ, Kutinsky IB, Robertson AD, Mehler PS. Dose related effects of methadone on QT prolongation in a series of patients with torsades de pointes. Pharmacotherapy 2003 June;23(6):8025. 28) Krantz MJ, Lewkowiez L, Hays H, Woodroffe MA, Robertson AD, Mehler PS. Torsades de pointes associated with very high dose methadone. Annals of Internal Medicine 2002 Sep;137(6):5014. 29) Appendix 3:prolongation of the QT interval in palliative care. [Online]. 2003 May [cited 2005 Nov 3]; Available from: URL: http://www.palliativedrugs.com/book.php?Appendix3 30) Leavitt, SB, Krantz MJ. Cardiac considerations during methadone maintenance treatment. Addiction Treatment Forum. Clinico Communications Inc. Jan 2004 [cited 2005 Mar 15] Available from: URL:http://www.atforum.com/SiteRoot/pages/ rxmethadone/cardiacmmt.sht mL 31) Gil M, Sala M, Anguera I, Chapinal O, Cervantes M, Guma JR, Segura F. QT Prolongation and torsades de pointes in patients infected with human immunodeficiency virus and treated with methadone. American journal of cardiology 2003 June;92(8):9957. 32) Walker G, Wilcock A, Carey AM, Manderson C, Weller R, Crosby V. Prolongation of the QT interval in palliative care patients. Journal of Pain and Symptom Management 2003 Sep;26(3):8559. 33) De Ponti F, Poluzzi E, Cavalli A, Recanatini M, Montanaro N. Safety of Nonantiarrhythmic drugs that prolong the QT interval or induce torsades de pointes. Drug Safety 2002; 24(4):26386. 34) Bruera E, Palmer JL, Bosnjak S, Rico MA, Moyano J, Sweeney C et al. Methadone versus morphine as a first line strong opioid for cancer pain : a randomized, doubleblind study. Journal of Clinical Oncology 2004 Jan 1; 22(1):18592. 35) Mathew P, Storey P. Subcutaneous methadone in terminally ill patients:manageable local toxicity. Journal of Pain and Symptom Management 1999 July;18(1):4952. 36) Centeno C, Vara F. Intermittent subcutaneous methadone administration in the management of cancer pain. Journal of Pain and Palliative Care Pharmacotherapy 2005;19(2):712. 37) Dhawan BN, Cesselin F, Raghubir R, Reisine T, Bradley PB, Portoghese PS, et al. Pharmacological Reviews. International Union of Pharmacology. XII. Classification of opioid receptors. 1196;48:56792. 38) Weinberg, DS, Inturrisi, CE, Reidenberg, B, Moulin, DE, Nip, TJ, Wallenstein, S, Houde, RW, Foley, KM. Sublingual absorption of selected opioid analgesics. Clinical Pharmacology & Therapeutics Sep 1988;44:35542. 39) Manfredi PL, Borsook D, Chandler SW, Payne R. Intravenous methadone for cancer pain unrelieved by morphine and hydromorphone: clinical observations. Pain 1997;70:99101. 40) Bruera, E, Pereira J, Watanabe S, Belzile M, Kuehn N, Hanson J. Opioid rotation in patients with cancer. Cancer 1996 Aug 15;78(4):8527. 41) Dart RC, Woody GE, Kleber HD. Prescribing methadone as an analgesic. Annals of Internal Medicine 2005 Oct;143(8):620. 42) Ripamonti C, Zecca E, Bruera E. An update on the clinical use of methadone for cancer pain. Pain 1993;70:109 115. 43) Tips for methadone pain management. ReadLinks Newsletter College of Pharmacists of British Columbia 2005 Jan/ Feb;30(1):9 44) Sandoval JA, Furlan AD, MailisGagnon A. Oral methadone for chronic noncancer pain. Systematic literature review of reasons for administration, prescription patterns, effectiveness, and side effects. Clinical Journal of Pain 2005;21:50312. 45) Mercadante S. Switching to methadone: “ad libitum” or fixed dose ratio? Letter to the editor. Palliative Medicine 2004;18:71. 46) Tse DMW, Sham MMK, Ng DKH, Ma HM. A reply to Dr. Mercadante Letters to the editor. Palliative Medicine 2004;18:723. 47) Anonymous (1996) Points to consider: the assessment of the potential for QT interval prolongation by non cardiovascular medicinal products. European Agency for the Evaluation of Medicinal Products: Committee for Proprietary Medicinal Products (EMEA); Committee for Proprietary Medicinal Products:CPMP/986/96 48) Twycross R. Switching to methadone. American Journal of Hospice Palliative Care 2001;5:359. 49) Anon. Newsletter [Online]. 2001 Feb [cited 2005 Nov 3]; Available from: URL:http://www.palliativedrugs.com 50) Bruera E, Newman C. Role of methadone in the management of pain in cancer patients. Oncology 1999;13(9) 127582; discussion 12858,1291. 51) Micromedex methadone monograph [Online]. [cited 2006 June 30]; Available from: URL: http://www.thomhc.com 52) Lipman AG Editor. Methadone:effective analgesia, confusion, and risk Editorial. Journal of Pain and Palliative Care Pharmacotherapy 2005;19(2);35. 53) Leavitt, SB MethadoneDrug* Interactions 3rd edition (* medications, illicit drugs, and other substances). Addiction Treatment Forum [cited 2006 Nov 28]; Available from: URL: www.atforum/SiteRoot/pages/rxmethadone/rxmethadone.sht mL Document1 Page 159 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 54) Woosley, RL. Drugs that prolong the QT interval and/or induce torsades de pointes. 2004 Dec 17 [cited 2005 Nov 3]; University of Arizona for Education and Research on Therapeutics Available at: URL: http://www.QTDrugs.org 55) Rheaume C, Aubin N, Gagnon B. Using methadone for pain control Information for you and your family. 2002 McGill University Health Centre Brochure. 56) Watanabe S. Methadone:the renaissance. Journal of Palliative Care 2001;17(2):11720. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 160 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix C Tramadol An Overview Tramadol briefly: · · · · · Is a synthetic opioid with analgesia provided via a weak OP3 (mu) receptor effect, and via inhibition of serotonin and noradrenaline reuptake.(4) Appears to provide neuropathic pain benefit.(1,4,9,10) Has a low incidence of constipation, nausea and dizziness compared to other opioids.(3) It has no major cardiovascular or blood pressure effects(3,4) and a low risk of respiratory depression.(1,5,16) May cause seizures; use cautiously in patients with epilepsy, head trauma, brain metastases, metabolic disorders, alcohol or drug withdrawal, CNS infections and with concurrent interacting drugs, e.g. SSRI’s, TCA’s, other opioids.(3,5,7,8) Tramadol is used for moderate pain, and is considered a step 2 analgesic on the World Health Organization 3 step ladder,(3,8,13,16) with a ceiling effect due to increasing seizure risk when dose exceeds 400 mg daily.(4,7,8,16) While tramadol is used in 8% of European palliative care units,(2) it’s role in Canada remains to be established. Not available in Canada as a single entity product, until December 2006, as a once daily extended release tablet in 150, 200, 300 and 400 mg strengths.(7) Tramadol is also available in combination with acetaminophen, each tablet contains 37.5 mg tramadol with 325 mg acetaminophen, and is licensed for pain treatment of five days or less. Dose 1 to 2 tablets q6h to a maximum of 8 tablets daily.(6) Tramadol more in depth: History · Developed in 1962, first used in 1977 (West Germany), introduced into Poland in 1992, USA in 1995 and the U.K in 1997.(1) · Worldwide over 50 million patients have received tramadol, as estimated by Bamigbade and Langford in 1998.(8) Market Size · US market size for tramadol estimated to be $US11.3 billion in June 2002 by the Canadian company Biovail.(12) So roughly, the Canadian market could be 1/10 th the amount, or approximately $C1.4 billion. Potency · Tramadol is twice as potent as codeine orally according to palliativedrugs.com.(5) But another review reference states potency as 1:1.(1) Document1 Page 161 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · Oral potency ratio of tramadol to morphine shown to be 1:4(8) but in a larger study involving cancer patients it was 1:10(16) CYP2D6 genotypes in patients might explain variation in equianalagesia in studies.(16) Tramadol 75 mg with 650 mg acetaminophen is equivalent to 400 mg ibuprofen for postoperative pain.(16) A single tablet of 100 mg oral tramadol is equivalent to 1000 mg acetaminophen for postoperative pain.(17) Sustained release morphine was shown to be more effective in severe cancer pain.(8) In Combination · · May be safely combined with NSAIDS.(8) Tramadol has no effect on prostaglandin synthesis and hence no ability to induce GI bleeding or reduced platelet activity.(13) Does not cause a withdrawal reaction when given to patients receiving morphine or methadone, yet similarly it does not prevent a withdrawal when substituted for potent opioids.(16) Metabolism and Excretion and Absorption · · · · · · · Mainly excreted by the kidneys (90%).(4,8,16) Following multiple oral administration of tramadol 100 mg four times daily, Cmax is 16% higher and AUC 36% higher than after a single 100 mg dose, indicating that oral bioavailablity increases to approximately 90100% on multiple administration, possibly due to saturated firstpass hepatic administration.(4) Has a total of 23 metabolites, all metabolites are almost completely excreted via the kidneys.(4) 7% of the population are poor metabolizers (due to the lack of the CYP2D6 enzyme) hence tramadol has little or no analgesic effect in these patients.(5) It was suggested that tramadol may have some efficacy in patients in which codeine is not effective and are CYP2D6 deficient,(13) although this has not been studied and is unknown. Africans (Nigerian’s studied) with the CYP2D6 #17 gene or Orientals with the CYP2D6 #10 gene may have altered tramadol metabolism, and reduce it’s ability to act as an analgesic.(16) Tramadol has not been well studied in renal and hepatic impairment, although some dosing suggestions appear.(16) It is contraindicated in severe hepatic failure and or severe renal failure (creatinine clearance less than 30 mL per minute).(7,14) High fat breakfast results in a 17% higher Cmax and 10% higher AUC.(4) Normal half life of 5 to 7 hours, is extended with age. The maximum dose in patients 75 years or older with good renal and hepatic function is 300 mg daily.(16) Document1 Page 162 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Adverse Effects · · · · · · · · 15% of patients have side effects. Dizziness 5%, nausea 5%, dry mouth 3%, sedation 2%, vomiting 1%.(16) Start with low doses to improve tolerance to side effects.(16) Nausea and vomiting respond to metoclopramide, phenothiazines and dexamethasone.(16) Anaphylactic reactions estimated incidence is 1 in 700,000(8) with an estimated fatality of one in 3.5 million.(8) Does not cause histamine release, so has a lower risk of pruritus.(13,16 Provides more acceptable side effects than tricyclic antidepressants or antiepileptics.(10) Dependency has occurred (range of 1 in 6000 to 1 in 100,000).(13) Most tramadol abuse is associated with polysubstance use and only 4.3% of the abuse is due to tramadol as a single agent.(16) Screen for previous history of substance abuse, as clinical commentary is to prescribe it cautiously in patients with a history of abuse or addiction.(11) Low abuse potential has been suggested(1,8) and is reflected in the drug scheduling worldwide and not subject to the same prescribing formalities as morphine.(8) Tramacet drug schedule permits a verbal prescription in Canada. Similarly, Zytram XL, is a prescription product, permitting prescribing as a verbal prescription. Potential interactions with ondansetron, (lowered tramadol efficacy) antipsychotics (including atypical), flecainide, quinidine, dextromethorphan.(13) Tramadol can cause additive CNS depression and respiratory depression when used with other agents that are CNS depressants e.g. alcohol, other opioids. (14) Tramadol may affect other drugs, causing increased digoxin and warfarin levels, or reduced carbamazepine levels.(14) Seizure Risk · · · · · Higher incidence of serotonin syndrome and convulsions when tramadol combined with interacting drugs. These include SSRI’s, TCA’S, MAO inhibitors, reversible inhibitors of monoadmine oxidase, other opioids, buspirone, LSD, cocaine, ecstasy, amphetamines, cyclobenzaprine, St. John’s wort, olanzapine, risperidone.(13,14,16) Activity of tramadol only partially reversed with naloxone (about 30%).(3) In tramadol overdose, naloxone administration may increase the risk of seizure.(7,14) Treatment of seizure in Zytram XL product monograph suggests the use of diazepam.(7) However in conversation with Ruth Hsu at Purdue medical information Jan 2, 2007, she stated that diazepam was considered representative as a class effect drug and that lorazepam would be a better choice, as has been suggested.(15) Seizure risk is much higher than other opioids. Occurs in one of 7000 patients,(16) median onset of 2 days.(13) Deaths – 12 in the USA associated with convulsions and tramadol use. In two, tramadol was used solely.(13) Document1 Page 163 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Additional Dosing Information · · · · · · Has been studied in 40 opioid naïve patients successfully.(1) Best to withdraw drug slowly and not stop abruptly.(14) There is a risk of withdrawal symptoms, anxiety, sweating, nausea, tremors, diarrhea, upper respiratory symptoms, piloerection, panic attacks, severe anxiety, paresthesias, and hallucinations (rarely).(14) Possibly problematic in palliative patients, no longer able to swallow. Not recommended in Canada in patients under age 18.(6,7) Tolerance appears to develop to a lesser extent in chronic use compared with other opioids.(13) B.C. Pharmacare palliative care nonbenefit drug (Zytram XL and Tramacet). Don’t confuse TRAMADOL with TORADOL (ketorolac). References: 1) Leppert W, Luczak J. The role of tramadol in cancer pain treatment – a review. Supportive Care Cancer 2005;13:5 17. 2) Klepstad P, Kaasa S, Cherny N, Hanks G, de Conno F. Pain and pain treatments in European palliative care units A cross sectional survey from the European Association for Palliative CareResearch Network. Palliative Medicine 2005;19:47784. 3) Shipton EA. Tramadol – present and future. Anaesthesia and Intensive Care 2000;28:35374. 4) Grond S, Sablotski A. Clinical pharmacology of tramadol. Clinical Pharmacokinetics 2004;43(13):879923. 5) Tramadol monograph Palliativedrugs.com[Online] [cited 2005 November 13] Available from: URL: http://www.palliativedrugs.com/pdi.ht mL 6) Tramacet product monograph [Online] July 14 2005 [cited 2005 November 13] Available from: URL: http://www.janssenortho.com/JOI/en/ 7) Zytram XL product monograph [Online] October 10 2006 [cited 2006 December 29] Available from: URL: http://www.purdue.ca/products/products.asp 8) Bamigbade TA, Langford. The clinical use of tramadol hydrochloride. Pain Reviews 1998;5:15582. 9) Arbaiza D, Vidal O. Tramadol in the treatment of neuropathic cancer pain: a doubleblind placebocontrolled study. Clinical Drug Investigation 2007;1:7583. 10) Duhmke RM, Cornblath DD, Hollingshead JRF. Tramadol for neuropathic pain [Review]. The Cochrane Database of Systematic Reviews 2005 Aug 24;4:129. 11) McDiarmid T, Mackler L, Schneider DM. Clinical inquiries. What is the addiction risk with Tramadol? Journal of Family Practice 2005 Jan;54(1):723. 12) Adis International Ltd. TramadolBiovail Corporation Drugs in R&D 2004;5(3):1823. 13) Close B. Tramadol:does it have a role in emergency medicine? Emergency Medicine Australasia 2005;17:7383. 14) Tramadol monograph. Clinical pharmacology 2006 [Online]. [cited 2005 November 8] Available from: URL: http://cpip.gsm.com 15) Lang ES, Andruchow JE. What is the preferred first line therapy for status epilepticus? Annals of Emergency Medicine 2006; 58:98100. 16) Tramadol David MP In: Davis MP, Glare P, Hardy J editors. Opioids in cancer pain Toronto: Oxford University Press; 2005. p. 6982. 17) Bandolier [Online] July 1999 Oral tramadol in postoperative pain. [cited 2006 Nov 13] Available from: URL: http://www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/AP003.ht mL Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 164 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Appendix D INCIDENT PAIN GENERAL PRINCIPLES SUFENTANIL GUIDELINES · Incident pain can be defined as a new or transiently worsening pain as a result of an action or activity. · Examples of clinical situations: · planned turns, transfers or ambulation · bathing · changing clothes · dressing changes or debridement · disimpaction · The management of incident pain can be difficult due to its rapid onset, intensity and transient nature. · Oral analgesics often do not have a rapid enough onset to be effective · Morphine or Hydromorphone oral solution would be an appropriate first choice in these patients, given 1 hour preincident. If not successful, try SC for rapid effect (1520 minutes) and ensure all other adjuvants have been tried. · In situations with severe incident pain and above not effective, Sufentanil can be considered Sufentanil · · · Sufentanil is a very potent synthetic opioid agonist that is rapidly absorbed sublingually and has a very short halflife. Sufentanil should NOT be used in opioid naïve patients If Sufentanil is initiated in the home, initial doses should be given under a monitored situation, i.e. RN in the home. R · · · · · Sufentanil is approximately 10x more potent than fentanyl (Sublimaze ) so proper labeling is crucial to prevent any confusion between these agents, especially in hospital. Sufentanil is available in 50mcg/ mL amps (1 mL). The onset of analgesic action may be as short as 35 minutes but wait 1015 min for full effect can last for 40 minutes. Each dose should be administered under the tongue approximately 10 minutes prior to the activity. The patient should be instructed not to swallow for up to 2 minutes. If the initial dose appears to be insufficient, the same dose may be repeated up to 2 additional times every 1015 minutes – see table below. Document1 Page 165 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · If a given dose is sufficient, the patient may appear drowsy for 1015 minutes. Increasing to the next step is undertaken if the maximum number of doses (3) is required to achieve comfort, or is insufficient to achieve comfort with activity. If a maximum of 3 doses at one level is required to achieve comfort, increase in a stepwise fashion as outlined below (no more frequently than hourly) Once dosage determined for each patient, repeat same dose for each incident (i.e. no need for incremental titration each time) Step Medication # micrograms SL (50mcg/ mL) 1 sufentanil 12.5mcg (0.25 mL) Q15min x 3 – if not effective go to step 2 2 sufentanil 25mcg (0.5 mL) Q15 min x 3 –if not effective go to step 3 3 sufentanil 50mcg (1 mL) Q15 min x 3 –if not effective go to step 4 4 sufentanil 100mcg (2 mL) Reference: http://palliative.info/IncidentPain.htm Monitoring · Monitor pain level (pain scores), sedation level and respiratory rate at baseline · At 5 minutes, 10 minutes and 15 minutes post dose(s), monitor for first episode of pain: pain level, sedation level and respiratory rate. Respiration: · If respiratory rate falls below 8/min and pain is still uncontrolled, discontinue protocol. Sedation: · If sedation level is 3 and pain is still uncontrolled, discontinue protocol. Sedation Level Assessment* 0 None : awake and alert 1 Mild: occasionally drowsy, easy to rouse 2 Moderate: frequently drowsy, easy to rouse 3 Severe: somnolent, difficult to rouse Adapted from http://www.bccancer.bc.ca/HPI/ChemotherapyProtocols/SupportiveCare/SCPAINSU.htm Document1 Page 166 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition RESPIRATORY SECRETIONS / CONGESTION Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Respiratory secretions and congestion are common in the terminal phase – 23 to 95%. Respiratory secretions (Type I in particular) are a strong predictor of death – 48% within 24 hours and 76% within 48 hours of onset. They are not usually distressing to patients in the terminal phase but, in contrast, may dominate the experience and memory of loved ones at the bedside.(114) Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptom of respiratory secretions and/or congestion. This guideline does not address disease specific approaches in the management of respiratory secretions and/or congestion. Definition of Terms Airway secretion refers to mucus secreted by the submucosal glands and goblet cells. The airway secretion can accumulate due to increased production, decreased mucociliary clearance and ineffective cough reflex.(1) Congestion Type I: Salivary Secretions accumulating when swallowing reflexes are inhibited.(15) Congestion Type II: Bronchial secretions which cannot be coughed up or swallowed.(15) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Assessment of Respiratory Secretions / Congestion Ongoing comprehensive assessment is the foundation of effective management of congestion and its related secretions, including interview, physical assessment, medication review, medical and surgical review, psychosocial and physical environment Document1 Page 167 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition review and appropriate diagnostics (see Table 1). Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family.(1, 3, 12) Patients with terminal secretions are often not responsive enough to be interviewed. The following questions are important to guide observation and may be asked to family members. Table 1: Respiratory Secretions/Congestion Assessment using Acronym O,P,Q,R,S,T,U and V (8, 12) * O P Onset Provoking / When did it begin? Can the secretions be cleared by coughing or swallowing? How often do they occur? What brings it on? What makes it better? What makes it worse? Is it positional? Palliating Q R What does it sound like? Quality Region / Where are the secretions? Throat? Chest? Radiation S T U Severity Treatment Understanding/ What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What does the person / family believe is causing this congestion? How is this symptom affecting the family? Is the person distressed? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Document1 Page 168 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 2 Diagnosis Identifying the underlying etiology of the secretions and congestion is essential in determining the interventions required.(3, 5, 12, 16) Type of Congestion Factors Contributing Increased fluid in airway • Oropharyngeal secretions (saliva) – Type I, accumulate near death • Tracheobronchial secretions (normal mucous production) – Type II, accumulate over several days as patients deteriorate and cough weakens • Nonrespiratory secretions (aspiration, blood, exudates, tumour debris) Decreased airway diameter • Increased resistance and turbulence • Edema • Smooth muscle hypertrophy • Intrinsic or extrinsic compression Ventilatory rate Recommendation 3 • Tachypnea • Altered, rapid breathing patterns Education The importance of education regarding treatment of respiratory secretions is to support the family at the bedside. Drowning and suffocation are not accurate descriptions of what is going on. “Death rattle” is a term to avoid, instead use the term congestion. Prepare the family by reviewing changes they can expect in the patient condition as death approaches.(2, 3, 7, 9, 1113) Recommendation 4 · · · · Treatment: Nonpharmacological Prevent aspiration with positioning.(2) Repositioning (move the patient from supine to lateral recumbent with head slightly raised) – to encourage drainage, maintain airway and decrease pooling of secretions.(1, 2, 4, 5, 712) Suction: o While it may seem to the family that suction should help, most secretions are usually below the larynx and inaccessible to suction.(3, 5, 14) o Routine use of suctioning in the hospital setting needs to be discouraged.(1, 2, 5, 8, 14) o The exception to this is fulminant pulmonary edema (copious “frothing”) or thick inspissated mucous, blood or other fluid in the throat or mouth – suctioning may be of value.(2, 3, 9, 12) Provide good mouth care.(3) Avoid over hydration if fluid built up in upper airways(5, 6, 9, 13, 14) especially in lung cancer patients.(10) Document1 Page 169 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Recommendation 5 Treatment: Pharmacological Anticholinergics are effective in reducing both saliva and mucus production. They should be used at the first sign of congestion as anticholinergics do not dry up secretions that are already present.(35, 9, 13, 16) There is no evidence to support a first choice anticholinergic for the treatment of terminal secretions and congestion. · Anticholinergics: o Atropine 0.4 to 0.8 mg S.C. q4h and q1h p.r.n.(35, 7, 14) o Atropine 1% eyedrops 1 to 2 drops q1 to 2h p.r.n. sublingual (3, 14) or buccal route.(7) (Anecdotal evidence as an alternative route to S.C. in the home) o Scopolamine (hyoscine hydrobromide) 0.3 to 0.6 mg S.C. q4 to 6h regularly and/or p.r.n.(3, 4, 7, 9, 12, 13) o Scopolamine transdermal patch 1.5 mg q72h; slow onset thus not indicated in terminal phase unless augmented with subcutaneous route for 8 to 12 hours.(35, 8, 14) o Glycopyrrolate 0.1 to 0.2 mg S.C. q6 to 8h regularly and/or p.r.n.; does not cross the blood brain barrier thus should be considered in nonobtunded patients.(1, 35, 12, 14) May be given orally(3) and sublingually.(3) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using respiratory / terminal secretions / congestions terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Chan KS, Sham M, M. K., Tse DMW, Thorsen AB. Palliative medicine in malignant respiratory diseases. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 587 618. 2. Leach R. Palliative medicine and nonmalignant, endstage respiratory disease. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. New York, New York: Oxford University Press Inc., New York; 2005. p. 895 916. 3. Jones C. Respiratory Congestion. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 381 9. 4. Rousseau P. Nonpain Symptom Management in the Dying Patient. Hospital Physician. 2002 Hospital Physician;38(2):51 6. 5. Beach P. Clinical Q&A. Treatment of Respiratory Congestion in Patients with Endstage Disease. Clinical Journal of Oncology Nursing 2003 JulAug; 7(4): 4535. 2003. 6. Lawrey H. Hyoscine vs glycopyrronium for drying respiratory secretions in dying patients. British Journal of Community Nursing 2005 Sep;.10(9):4214. 7. Sorenson HM. Managing Secretions in Dying Patients. Respiratory Care. 2000 November 2000;45(11):1363 4. 8. Fairbrother CA, Paice JA. Life’s Final Journey: The Oncology Nurse’s Role. Clincal Journal of Oncology Nursing. October 2005;9(5):575 9. 9. Morita T, Tsunoda J, Inoue S, Chihara S. Risk factors for death rattle in terminally ill cancer patients: A prospective exploratory study. Palliative Medicine. January 2000;14(1):19 23. 10. Morita T, Hyodo I, Yoshimi T, Ikenaga M, Tamura Y, Yoshizawa A, et al. Association between hydration volume and symptoms in terminally ill cancer patients with abdominal malignancies. Annals of Oncology. 2005 Apr;16(4):640 7. Document1 Page 170 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 11. Wee BL, Coleman PG, Hillier R, Holgate SH. The sound of death rattle II: How do relatives interpret the sound? Palliative Medicine. April 2006;20(3):177 81. 12. Bennett M, Lucas V, Brennan M, Hughes A, O’Donnell V, Wee B. Using antimuscarinic drugs in the management of death rattle: evidencebased guidelines for palliative care. Palliative Medicine. September 2002;16(5):369 74. 13. Kass RM, Ellershaw J. Respiratory Tract Secretions in the Dying Patient: A Retrospective Study. Journal of Pain and Symptom Management. October 2003;26(04):897 902. 14. Bickel K, Arnold B. Fast Fact and Concept #109: Death rattle and oral secretions. March 2004; Available from: http://www.eperc.mcw.edu/fastFact/ff_109.htm 15. Spruyt O, Kausae A. Antibiotic use for infective terminal respiratory secretions. Journal of Pain and Symptom Management.1998;15(2):2634. 16. Whiting N. Cough. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 171 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition PALLIATIVE SEDATION ***This section is currently under development*** See http://iportal.northernhealth.ca > clinical resources > Palliative Care > Documents > Victoria Hospice Palliative Sedation Guidelines Document1 Page 172 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition PSYCHOSOCIAL CARE ***This section is currently under development*** Document1 Page 173 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition SPINAL CORD COMPRESSION Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) with advanced life threatening illness and experiencing the symptom of spinal cord compression. This guideline does not address disease specific approaches in the management of spinal cord compression. The vertebral column is the most common site of skeletal metastasis.(1) Seventy percent of patients dying from cancer have spinal metastases at autopsy.(1) Cord compression occurs in 5% to 10% of all patients with malignancy (18) but account for 25% of all central nervous system tumours.(3) Definition of Terms Spinal Cord Compression develops when the spinal cord is compressed by a tumour, abscess or other lesion. It is regarded as a medical emergency independent of its cause, and requires swift diagnosis and treatment to prevent longterm disability due to irreversible spinal cord injury.(9, 10) Standard of Care 1. Assessment 2. Diagnosis 4. Prognosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Assessment of Spinal Cord Compression Ongoing comprehensive assessment is the foundation of effective management of spinal cord compression, including interview, physical assessment, medication review, medical and surgical review, psychosocial review, review of physical environment and appropriate diagnostics (see Table 1). Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family. Document1 Page 174 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1: Spinal Cord Compression Assessment using Acronym O,P,Q,R,S,T,U and V * O P Onset Provoking / When did it begin? How long have you had the pain, constipation, weakness? Have you had this before? What brings the pain on? What makes it better? Does cough, sneeze or pressure make it worse? Palliating Q R What does it feel like? Can you describe it? Is it a bandlike pain? Quality Region / Where is it? Does it spread anywhere? Radiation S T U Severity Treatment What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? Understanding/ How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Symptoms: · · Pain is the presenting symptom in 90 to 95% of patients(1, 11) Two types of pain:(1) Local back pain (midline/paravertebral) nearly always present.(1) o Usually constant, close to site of lesion.(1) o Relieved by sitting or standing up (as opposed to disc disease which is relieved by laying down). (1, 8) o Exacerbated by any increase in intrathoracic pressure (sneeze, cough, Valsalva maneuver, straining at stool).(1, 4) Document1 Page 175 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Above historic points may be only clue to impending spinal cord compression.(1) Radicular pain from spinal root compression occurs in 66% of patients.(1) o More common with lumbosacral (90%) and cervical (79%) metastases than with thoracic metastases (55% of cases).(1) o Patients complain of a band or girdle of pain/tightness radiating from back to front; in extremities, radicular pain usually unilateral.(1) o Exacerbated by recumbency, movement, cough, sneeze, Valsalva maneuver.(1, 3, 12) o Worse at night.(1, 3, 8, 12) o Improved by sitting or standing.(1, 8) o Radiates in a dermatomal pattern.(1) o May produce numbness and tingling (cervical, thoracic or lumbar root).(1) When progresses numbness usually precedes weakness. o May resemble pain from intervertebral disc disease, pleurisy, cholecystitis or pancreatitis.(1) o Distinguish from brachial or lumbosacral plexus involvement.(1) o Localizes the lesion within one or two vertebral segments.(1) Weakness in legs is the next symptom if left untreated (76% of patients).(1) o Experienced as stiffness, dragging of a limb or unsteadiness.(1, 12) Sensory disturbances may accompany or be preceded by (in 51% of patients).(1) o Numbness usually begins in the toes, gradually ascends to level of cord compression (usually without paresthesias).(1, 12) o Sensation of coldness.(1, 12) o Upper limit of sensory level often one to two vertebral bodies below site of compression.(1) o Sensory loss progresses to ataxia (3% of patients).(1) Autonomic dysfunction (57% of patients).(1) o Early signs: loss of bladder control, hesitancy, urgency. o Late signs: urinary retention, overflow incontinence.(1, 12) o Constipation.(1) o Loss of perspiration below level of the lesion.(1) o Sexual difficulties.(12) Signs and symptoms probably not due solely to compression of cord; ischemia secondary to vascular involvement may also be a factor (especially when cord compression develops suddenly over a few hours).(1, 8) o · · · · · Distribution:(1, 3, 5, 12) · Thoracic spine – 70% (8,13) which has a smaller ratio of spinal canal to cord diameter than the other two spinal segments.(8) · Multiple contiguous levels – 10% to 38%.(7) · Lumbosacral spine – 20%. · Cervical spine – 10%. Document1 Page 176 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Incidence In Malignancy:(1) · Lung – 16% · Breast – 12% · Unknown primary – 11% · Lymphoma – 11% · Myeloma – 9% Recommendation 2 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. The most significant intervention in the management of spinal cord compression is identifying underlying cause(s) and treating as appropriate. While underlying cause(s) may be evident, treatment may not be indicated, depending on the stage of the disease. Whether or not the underlying cause(s) can be relieved or treated, all patients will benefit from management of the symptom using education, specialist intervention or medications. Identifying the underlying etiology of the spinal cord compression is essential in determining the interventions required. The importance of early diagnosis cannot be overemphasized; symptoms are usually present for some weeks before neurological emergency occurs.(3, 4) In rural communities where treatment may require travel the importance of early diagnosis is even more crucial. · Extent of diagnostic workup indicated in any given case depends on overall condition of patient. In patients expected to live more than 1 to 2 months and who are not already paraplegic the following tests are indicated:(1) o Evidence of epidural metastases may be seen on plain xrays in approximately 85% of patients(1) but only predicts the level of compression in 19%.(3) o Urgent referral for CT scans and MRI improves early detection. MRI scans are more sensitive than CT Scans and are the standard for diagnosis.(3, 6, 7) Whole spine MRI is more sensitive in detecting small CNS metastases that can be missed with other imaging methods. (6,11) Myelography has a place where CT scan and MRI are not available.(4) Recommendation 3 · · Prognosis The degree of neurologic function at diagnosis and the start of treatment is the most significant factor in determining the recovery of function.(1, 14) Rapid onset (less than 48 hours) and progression of symptoms are poor prognostic indicators.(2) Patients who are not mobile at presentation do not Document1 Page 177 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · generally regain the ability to walk.(6) Of patients who are paraplegic pre treatment, only 10% will regain ambulation after treatment.(13) If the patient has been paralyzed for more than 48 hours, the chance of neurological recovery is very poor.(3) “Emergency” treatment at this point may not be indicated but palliative radiation for pain management may be beneficial (per British Columbia Cancer Agency).(15) Start I.V. corticosteroids to reduce edema and improve neurological function while completing diagnostic workup when history and physical examination suggest spinal cord compression.(1, 3, 16) · Spinal cord compression is an emergency necessitating immediate assessment and treatment(2, 3, 6, 14) requiring urgent consultation of the radiation oncologist and neurosurgeon at the closest available site.(10) A Radiation Oncologist will treat with radiotherapy on weekends.(13) Recommendation 4 · · Patients at risk should be identified and taught the signs and symptoms of spinal cord compression and the urgency of reporting promptly.(1) Explain procedures and details of ongoing investigations with patients and family.(6) Recommendation 5 · · · Education Treatment: Nonpharmacological Malignant spinal cord compression should be individualized and should take into consideration pretreatment ambulatory status, previous treatment, comorbidities, technical surgical factors, the presence of bony compression and spinal instability, potential surgical complication, potential radiotherapy reactions and patient preferences.(17) Management requires a combined effort from the family physician, radiation oncologist and spinal surgeon.(14) Radiation therapy should be started immediately after diagnosis.(1, 6, 13) o Radiation therapy provides definitive treatment in most patients.(2, 3, 5, 8, 14, 16) Indications for radiation therapy include known radiosensitive tumour and no spinal instability(1, 5, 7, 11, 17) and for palliative therapy in patients who present with paraplegia.(7) o Radiation therapy alone gives equivalent results to laminectomy plus adjuvant radiation therapy(1, 4) and is effective in over 85% of cases of spinal cord compression.(6) o Patients who are ambulatory at the time of the diagnosis have a higher probability of obtaining good response to treatment and a longer survival.(3) o Patients who experience progressive neurological deficits despite receiving radiotherapy should be considered candidates for urgent surgical decompression and/or stabilization.(7) Document1 Page 178 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · Surgery may be considered if the patient is ambulatory and otherwise stable with good performance status.(13) o Surgery is the first choice where the site of the primary tumour is unknown, where there is relapse after radiation treatment, and in cases of spinal instability or vertebral displacement.(8, 11) It should also be considered when neurological symptoms progress during radiotherapy, in plegia of rapid onset, or where tumours are not radiosensitive. (4, 12, 14) Rehabilitation must commence on diagnosis and must encompass the skills of various professionals. Ensure that goals are short term and attainable so as to achieve the best possible quality of life.(6, 8) o If patient immobile, treat as if they have an unstable spine during repositioning.(6) o Apply antiembolic stockings if patient has impaired mobility.(6) o Ensure emotional and psychosocial support for patient and family.(6) Recommendation 6 Treatment: Pharmacological Dexamethasone 10 to 100 mg I.V. STAT(3, 4, 11) then 16 to 96 mg PO daily, then taper over 10 to 14 days after improvement or irreversibility.(1, 5, 11) · · · Shown to improve neurologic function and relieve pain, reduce edema and have a direct oncolytic effect.(1) Dexamethasone may also temporarily prevent the onset of cord ischemia.(2) In patients with short prognosis or poor performance status, corticosteroids may be the only treatment feasible.(1, 2) Consider the use of prophylactic heparin if the patient has impaired mobility.(6) Severe pain will usually require rapid titration of an opioid drug to achieve analgesia.(1) References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using spinal cord compression terms in conjunction with palliative/hospice/end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Waller A, Caroline NL. Spinal Cord Compression. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA; 2000. p. 3018. 2. Dean M, Harris JD, Regnard C, Hockley J. Emergencies. Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 20119. 3. Downing GM. Neurological Spinal Cord Compression. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 4702. 4. Caraceni A, Martini C, Simonetti F. Neurological problems in advanced cancer. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 70326. Document1 Page 179 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 5. Klimo P, Kestle JRW, Schmidt MH. Treatment of metastatic spinal epidural disease: A review of the literature. Neurosurgery Focus. 2003 November;15(5):19. 6. Crawford B. Spinal cord compression management. In: Dougherty L, Lister S, editors. The Royal Marsden Hospital Manual of Clinical Nursing Procedures. 6th ed. Oxford: Blackwell Publishing; 2004 p67786 7. Ryken TC, et al. Evidencebased review of the surgical management of vertebral column metastatic disease. Neurosurgery Focus. 2003 November;15(5):110. 8. Guo Y, Shin KY. Rehabilitation Needs of Cancer Patients. Critical Reviews in Physical and Rehabilitation Medicine. 2005;17(2):8399. 9.Wikipedia.Spinalcordcompressiondefinition.2005;Availablefrom: http://en.wikipedia.org/wiki/Spinal_cord_compression. 10.BCCancerAgency.SpinalTumours.CancerManagementGuidelines2004;Available from: http://www.bccancer.bc.ca /HPI/CancerManagementGuidelines/NeuroOncology/ManagementPolicies/SpinalTumours.htm 11. Loblaw DA, Perry J, Chambers A, Laperriere NJ. Systematic Review of the Diagnosis and Management of Malignant Extradural Spinal Cord Compression: The Cancer Care Ontario Practice Guidelines Initiative’s Neuro Oncology Disease Site Group. J Clin Oncol. March 20, 2005;23(9):202837. 12. WredeSeaman LD. Management of Emergent Conditions in Palliative Care. Primary Care: Clinics in Office Practice. June 2001;28(2):317 28. 13. British Columbia Cancer Agency Professional Practice Nursing. Alert Guidelines: Spinal Cord Compression. Available from: http://www.bccancer.bc.ca /NR/rdonlyres/5FF39B8B04B9469882F8D622689EDDED/7592/SpinalCordCompression.pdf 14.BritishColumbiaCancerAgency.SpinalTumours.February2004;Guideline.Available from: http://www.bccancer.bc.ca /HPI/CancerManagementGuidelines/NeuroOncology/ManagementPolicies/SpinalTumours.htm 15. BC Cancer Agency. Metastatic Disease. Cancer Management Guidelines 2006 cited; Available from: http://www.bccancer.bc.ca/HPI/CancerManagementGuidelines/Lung/6ManagementPolicies/641NonSmallCellLungCa ncer/14PalliativeRadiotherapyforMetastaticDiseaseTAnyNAnyM1.htm 16. Ciezki JP, Komurcu S, Macklis RM. Palliative Radiotherapy. Seminars in Oncology. 2000 February;27(1):903. 17. Chow E, Wu J, Loblaw A, Perez CA. Radiotherapeutic approaches to metastatic disease. World Journal of Urology.2003;21:22942. Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 180 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition SPIRITUAL CARE ***This section is currently under development*** Document1 Page 181 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition SUPERIOR VENA CAVA OBSTRUCTION ***This section is currently under development*** Causes · Compression or invasion by a mediastinal tumour Clinical features · General o Dyspnea, cyanosis, neck vein distension, edema of the face, neck and upper extremities · A mediastinal tumour may cause cough, dysphagia, hoarseness or chest pain. · Neurologic symptoms include blurred vision, dizziness, syncope and headache. Diagnosis · Clinical presentation, CXR, CT scan Treatment · General – Fluid and salt restriction with diuretic (furosemide), oxygen, elevation of the head of the bed. · Dexamethasone 1624mg PO/SC/IV daily · Treatment of tumour o radiotherapy or chemotherapy for sensitive tumours o Further treatment will depend on stage of disease and prognosis The above information provided from the first edition of the NH Palliative Care Guidelines and Protocols, December 2004. Document1 Page 182 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition TWITCHING / MYOCLONUS / SEIZURES Rationale This guideline is adapted for interprofessional primary care providers working in various settings in Northern Health, British Columbia and any other clinical practice setting in which a user may see the guidelines as applicable. Scope This guideline provides recommendations for the assessment and symptom management of adult patients (age 19 years and older) living with advanced life threatening illness and experiencing the symptoms of myoclonus, twitching or seizures. This guideline does not address disease specific approaches in the management of myoclonus, twitching or seizures. Seizures may be the first indication of a brain tumour. They occur in up to 50% of palliative patients with a primary brain tumour(1) in 20% to 45% of patients with brain metastases,(2,3) while up to 70% of patients with HIV infection can have seizures as a complication.(2) It is more difficult to control seizures in patients with primary brain tumours.(3) Definition of Terms Twitching refers to an involuntary muscle contraction; it tends to be repetitive, unwanted, lacking obvious cause, and is not considered part of the normal operation of the body.(4) Myoclonus is defined as involuntary single or irregularly repetitive movements of one part of the body associated with either muscle contraction (positive myoclonus) or brief loss of muscle tone (negative myoclonus).(5) Simple partial seizures exhibit a normal level of consciousness; only a selective area of the cortex participates in the seizure (affecting partial motor, sensory, autonomic and affective functions). If these precede a generalized partial complex seizure they are called an “aura”. Generalized tonicclonic seizures start with a sudden loss of consciousness, followed by diffuse muscle rigidity and cyanosis. After one minute myoclonus and muscle fasciculations occur for one to two minutes, followed by the postictal phase. Partial complex seizures combine focal symptoms with an altered state of consciousness. These are the most common type of seizures seen in palliative care adults. These can last on average three minutes and are followed by a postictal phase.(2) Document1 Page 183 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Status epilepticus is a seizure lasting 5 minutes or repeated seizures one after another without regaining consciousness.(5, 6) Standard of Care 1. Assessment 2. Diagnosis 3. Education 4. Treatment: Nonpharmacological 5. Treatment: Pharmacological Recommendation 1 Assessment of Twitching / Myoclonus / Seizures Ongoing comprehensive assessment is the foundation of effective management of twitching/myoclonus/seizures, including interview, physical assessment, medication review, medical and surgical review, psychosocial review, review of physical environment and appropriate diagnostics (see Table 1). Assessment must determine the cause, effectiveness and impact on quality of life for the patient and their family. Document1 Page 184 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Table 1: Twitching / Myoclonus / Seizures Assessment using Acronym O,P,Q,R, S,T, U and V * O P When did it begin? How long does it last? How often does it occur? Onset Provoking / What brings it on? What makes it better? What makes it worse? Palliating Q R What does it feel like? Can you describe it? How do you feel afterwards? Quality Region / What happens when you experience twitching or myoclonus or seizure? Radiation S T U Severity Treatment Understanding/ What is the intensity of this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Right now? At best? At worst? On average? How bothered are you by this symptom? Are there any other symptom(s) that accompany this symptom? What medications and treatments are you currently using? How effective are these? Do you have any side effects from the medications and treatments? What medications and treatments have you used in the past? What do you believe is causing this symptom? How is this symptom affecting you and / or your family? Impact on You V Values What is your goal for this symptom? What is your comfort goal or acceptable level for this symptom (On a scale of 0 to 10 with 0 being none and 10 being worst possible)? Are there any other views or feelings about this symptom that are important to you or your family? * also include a Physical Assessment (as appropriate for symptom) Recommendation 2 Diagnosis Management should include treating reversible causes where possible and desirable according to the goals of care. The most significant intervention in the management of twitching/myoclonus/seizure is identifying underlying cause(s) and treating as appropriate. While underlying cause(s) may be evident, treatment may not be indicated, depending on the stage of disease. Document1 Page 185 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Whether or not the underlying cause(s) can be relieved or treated, all patients will benefit from management of the symptom using education or medication. Determine if the patient is experiencing twitching, myoclonus or seizure and the underlying etiology to determine the interventions required.(7) · · Causes can be multifactorial.(5) Common causes include: o Brain tumours – primary or metastatic.(13, 5, 6, 810) o Metabolic causes (hypoglycemia, hyponatremia, renal or hepatic failure, and hypercalcemia).(2, 3, 511) Hypoglycemia is the most common metabolic cause of seizure activity. Hypoglycemia can be caused by prolonged seizure activity.(1) o Drug toxicity – opioid induced neurotoxicity.(13, 57, 10) Myoclonus or seizures caused by opioid toxicity are a late phase adverse effect.(9) Other causes are: o Alzheimer’s Disease.(10) o Cerebral irritability of predeath restlessness. o CreutzfeldtJacob disease. o Drug withdrawal (alcohol, barbiturates, benzodiazepines, opioids).(2, 6, 8, 10) o Encephalopathy.(6) o Hypoxia.(6, 8) o Infection(3, 6) – HIV toxoplasmosis, cryptococcus, tuberculosis, JC virus (progressive multifocal leukoencephalopathy)(2, 3, 8, 10, 11) or CNS infection.(3, 10) o o o o o o o Intracerebral hemorrhage.(3, 5, 6) Organic Brain Syndrome.(10) Preexisting epilepsy or seizure disorder.(58, 10) Radiationinduced edema/necrosis.(3) Stroke or transient ischemic attack.(7, 8, 10) Trauma.(5, 11) Twitching can be caused by; pinched nerve or nerve injury, stimulant abuse, Parkinson’s disease, epilepsy, amyotrophic lateral sclerosis and benign fasciculation syndrome. Recommendation 3 Education Myoclonus may disrupt sleep, make coordinated movements difficult and be bothersome to patients or families.(7) Patients and families should be educated about improving sleep hygiene. Information about normal sleep and sleep hygiene can be found on the Canadian Sleep Society website at: http://www.css.to/sleep/normal_sleep.pdf Advice to family for seizure at home:(3, 8) · Try to make sure that the patient does not fall or bump into any sharp objects. · Do not attempt to restrain the patient. · Do not try to force anything into the patient’s mouth. · When the seizure stops, turn the patient onto his/her side. Document1 Page 186 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · The patient will be sleepy for a while after the seizure. If the seizure does not stop by itself in about 5 to 10 minutes or if another seizure occurs soon after the first, call for medical assistance. Do not shout or expect verbal commands to be obeyed.(3) Seizures are frightening to the patient and family. Take time afterward to explore concerns of the patient and family and offer honest reassurance.(1, 3) Address questions such as:(8) · Will the patient swallow his/her tongue or choke to death during a seizure? · Will there be permanent brain damage from a seizure? · Will seizures hasten death? Recommendation 4 Treatment: Nonpharmacological · Clear the area of hard or sharp objects to prevent injury during the seizure.(3, 8) · Maintain airway by lifting up the patient’s chin.(8) · When seizure is over, place in stable side position (recovery position) until he/she is alert.(8, 11) · Draw blood test for laboratory investigation(8) (if the patient in hospital and thought to be necessary). · Administer oxygen for patients with status epilepticus.(8) Recommendation 5 Treatment: Pharmacological Twitching/Myoclonus: · All opioid analgesics can produce myoclonus. Mild and infrequent myoclonus is common. If the dose cannot be reduced due to persistent pain, consider opioid rotation or symptomatic treatment.(7, 9, 12, 13) Hydration should be considered(14) (See Northern Health Hospice Palliative Care Symptom Guideline for Dehydration). · When myoclonus is severe or there is concern that generalized seizures can occur there is limited evidence to support the use of baclofen, diazepam, clonazepam, midazolam, valproic acid or dantrolene sodium.(9) Consider opioid rotation ie) morphine to hydromorphone or fentanyl.(2,14) · Benzodiazepines are the primary symptomatic treatment.(7) Lorazepam is often used as it can be given orally, SL or S.C.. Clonazepam and valproic acid also have been used for the treatment of myclonus.(3) · Midazolam can be used for terminal restlessness and myoclonus (especially due to opioid toxicity).(8) Use: · Clonazepam starting dose 0.5 to 1 mg PO at bedtime or b.i.d. if necessary. · Lorazepam 0.5 to 2 mg SL or S.C. q4h or p.r.n. · Diazepam 2.5 to 5 mg PO or rectally q12h p.r.n. Document1 Page 187 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition Seizure: · If a seizure has occurred and recurrence is likely, then treatment is warranted.(5) · Prophylactic anticonvulsant therapy in patients with brain tumours or metastases is controversial. It has not been shown to provide an advantage in seizure control.(13) · Seizure prophylaxis should be instituted after the first seizure.(8) · Clonazepam can be used for the temporary treatment of seizures not controlled by ongoing therapy.(2) Start with clonazepam 0.5 mg PO t.i.d., and then increase by 0.5 mg every 3 days until symptoms are controlled. Abrupt withdrawal of clonazepam after longterm use may precipitate status epilepticus taper dosage instead.(8) · Although diazepam has been the benzodiazepine of choice for status epilepticus, recent evidence indicates that lorazepam may be more beneficial because it provides longer control of seizures and produces less cardiorespiratory depression.(16) · Gabapentin can be used for adjuvant therapy of partial seizure and tonicclonic seizures.(1) Starting dose is 300 mg t.i.d. to q.i.d PO with maintenance dose of 900 to 3600 mg per day PO.(1) · Midazolam can be given I.V. or S.C. or PO, with the quickest onset by I.V. route. I.M. route is not recommended. Use lower dose in older adults (1 to 2 mg).(2) · Phenobarbital is effective in both partial and generalized tonicclonic seizures.(2) · Phenothiazines should be avoided in patients in whom cerebral irritation is a potential problem.(15) · Consider starting or increasing dexamethasone PO or S.C. in seizures from brain tumour or metastasis.(5) Dexamethasone should not be the only drug used, even if only one seizure has occurred.(5) · Response to pharmacological therapy is individualized and highly variable. The dose should be titrated to clinical response rather than to a specific serum level.(1) For Simple Partial Seizure use: · Lorazepam 1 to 2 mg SL or S.C. STAT then 1 to 2 mg q4h to q6h. · Phenytoin SR capsules 300 mg PO daily(1) or (100 mg t.i.d. if using liquid). Titrate dose to achieve therapeutic serum levels.(5) For Generalized Tonic/Clonic Seizures use: Initial management with: · Lorazepam 4 to 8 mg I.V. or S.C. or SL STAT(3, 5) then 2 to 4 mg q4h to q6h. · Diazepam 10 mg STAT,(3) repeated q15min (maximum 30 mg in 8 hours) until settled. · Phenobarbital 80 to 120 mg S.C. q15min until settled. · Phenytoin 10 to 15 mg per kg I.V. STAT, at 25 to 50 mg per minute.(3) Do not mix with other IV medications or D5W. Then start on: Document1 Page 188 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · Phenobarbital 80 to 240 mg S.C. q12h with 120 mg q1h S.C. p.r.n. OR as a continuous S.C. infusion at 1200 mg per 24h (end stage care).(3, 15) Midazolam 5 mg S.C. STAT then 1 to 4 mg per hour by continuous S.C. infusion to manage the seizures. Phenytoin 300 mg daily PO at bedtime.(8) Valproic Acid 20 mg per kg loading dose followed by 3 to 5 mg per kg per min infusion(5) or liquid rectally. Injectable available through Health Canada special access program. Status Epilepticus: · · · Status epilepticus should be controlled, even in the unconscious patient near death, because of the distress that continuous seizures cause to the patient’s family.(8) Lorazepam is the drug of choice for status epilepticus.(2, 5) Preferred routes are I.V. or rectally, I.M. is not recommended.(2) Do not infuse faster than 2 mg per minute.(2) Phenytoin should be used in benzodiazepine refractory status epilepticus by I.V. infusion. In older adults use a lower dose (15 mg per kg).(2) Check serum phenytoin level after 10 to 14 days of therapy and again if seizures occur.(8) Use: (5) First line: · Lorazepam 2 to 8 mg I.V. or S.C. or SL STAT then q10 to 20 min until controlled OR Midazolam 5 to 10 mg S.C. OR Diazepam 10 to 20 mg I.V. or rectally (if available). · Phenytoin 2550 mg per min I.V. until seizure stops or maximum loading dose of 20mg per kg. Do not mix with other IV medications or D5W. · Valproic acid loading dose 20 mg per kg then 3 to 5 mg per kg per min infusion. Injectable available through Health Canada special access program. Failing control: · Phenobarbital 120 mg S.C. or I.V. and titrating to control. References Information was compiled using the CINAHL, Medline (1996 to April 2006) and Cochrane DSR, ACP Journal Club, DARE and CCTR databases, limiting to reviews/systematic reviews, clinical trials, case studies and guidelines/protocols using twitching/myoclonus/seizure terms in conjunction with palliative/hospice/ end of life/dying. Palliative care textbooks mentioned in generated articles were hand searched. Articles not written in English were excluded. 1. Capital Health Regional Palliative Care Program. Chronic Seizure Guideline for Pharmacological Management in PalliativeCare Patients. March 20, 2003. Available from: http://www.palliative.org /pc/clinicalinfo/Clinical%20Practice%20Guidelines/PDF%20files/Chronic%20Seizure%20Pharmacological%20Manag ement%20in%20Palliative%20Care.pdf Document1 Page 189 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition 2. Caraceni A, Martini C, Simonetti F. Neurological problems in advanced cancer. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 70326. 3. Krouwer HGJ, Pallagi JL, Graves NM. Management of Seizures in Brain Tumour Patients at the End of Life. Journal of Palliative Medicine. 2000;3(4):46575. 4. Twitching definition. [cited August 31st, 2006]; Available from: http://en.wikipedia.org/wiki/Twitching 5. Downing GM. Seizures. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed. Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 46975. 6. Capital Health Regional Palliative Care Program. Acute Seizure (Status Epilepticus) Protocol for Pharmacological Management in Palliative Care Patients. March 20, 2003. Available from: http://www.palliative.org /pc/clinicalinfo/Clinical%20Practice%20Guidelines/PDF%20files/Acute%20Seizure%20Pharmacological%20Manage ment%20in%20Palliative%20Patients.pdf 7. DeMonaco N, Arnold R. Myoclonus. May 2004; [cited 2006 August]; Available from: http://www.aahpm.org/cgi bin/wkcgi/view?status=A%20&search=462&id=530&offset=0&limit=25 8. Waller A, Caroline NL. Seizures. Handbook of Palliative Care in Cancer. 2nd ed. Boston, MA: Butterworth Heinemann;2000. p. 2957. 9. Watanabe S, Tarumi Y. Neurological effects: opioids. In: MacDonald N, Oneschuk D, Hagen N, Doyle D, editors. Palliative Medicine A case based manual 2nd ed. New York: Oxford University Press Inc.; 2005. 10. Baldwin K, Miller L, Scott JB. Proactive identification of seizure risk improves terminal care. American Journal of Hospice and Palliative Care. August 2002;19(4):2518. 11. Dean M, Harris JD, Regnard C, Hockley J. Emergencies. Symptom Relief in Palliative Care. Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 20119. 12. Hanks G, Cherny NI, Fallon M. Opioid analgesic therapy. In: Doyle D, Hanks G, Cherny NI, Calman K, editors. Oxford Textbook of Palliative Medicine. 3rd ed. Oxford, England: Oxford University Press; 2004, paperback 2005. p. 335. 13. Dean M, Harris JD, Regnard C, Hockley J. Managing the adverse effects of analgesics. Symptom Relief in Palliative Care.Oxford, United Kingdom: Radcliffe Publishing; 2006. p. 5360. 14. Black F, Downing GM. Pain Analgesics. In: Downing GM, Wainwright W, editors. Medical Care of the Dying. 4th ed.Victoria, B.C. Canada: Victoria Hospice Society Learning Centre for Palliative Care; 2006. p. 187251. 15. Stirling LC, Kurowska A, Tookman A. The Use of Phenobarbitone in the Management of Agitation and Seizures at the End of Life. Journal of Pain & Symptom Management. May 1999;17(5):3638. 16. Diazepam monograph 2006 Gold Standard Multimedia [cited 2005 Dec 1]; Available from: URL:http://cpip.gsm.com/ Approved by: Northern Health Hospice Palliative Care Consult Team, October 2008 Document1 Page 190 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition INDEX · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · A Accupuncture / Accupressure............................................................. Page 67,108 Acetaminophen............................................................................ Page 18,138,139 Addiction.................................................................................................. Page 125 Adenose Triphosphate ............................................................................ Page 117 Adjuvant analgesics................................................................... Page 125,139140 Advance Care Planning............................................................................. Page 16 Agitation .................................................................................................... Page 48 Albumin ................................................................................................ Page 81,93 Allergy .............................................................................................. Page 126,150 ALS................................................................. (see Amyotrophic Lateral Sclerosis) Amantadine ............................................................................................. Page 141 Amitriptyline ....................................................................... Page 17,19,62,141,154 Amyotrophic Lateral Sclerosis ......................................................... Page 13,38,66 Analgesic Ladder............................................................... (see W.H.O. principles) Anemia ............................................................................................ Page 66,81,83 Anorexia ................................................................................. Page 43,83,101,113 Anticholinergics .................................................................................. Page 17,169 Anticonvulsants .................................................................................. Page 58,141 Antidepressants....................................................................................Page 6062 Antiemetics......................................................................... Page 103,108,109,112 Antitussives ............................................................................................... page 39 Anxiety....................................................................................................... Page 66 Aprepitant ................................................................................................ Page 109 ASA ......................................................................................................... Page 138 Ascites........................................................................................................ Page21 Asthenia ............................................................................................. (see fatigue) Ativan ........................................................................................... (see lorazepam) Atropine ....................................................................................... Page 17,109,169 Autonomic dysfunction ............................................................................ Page 176 B B&O Suppository ..................................................................................... Page 141 Back pain................................................................................................. Page 175 Baclofen ....................................................................................... P age 19,90,141 Benzodiazepines ............................................................... Page 54,58,69,141,187 Bisphosphonates................................................................................ Page 95,140 Bladder Spasm ........................................................................................ Page 141 Bleed ..................................................................................... (see exsanguination) Bone pain/metastases ........................................................................ Page 92,140 Botulinum Toxin......................................................................................... Page 17 Bowel Obstruction ............................................. (see malignant bowel obstruction) Bowel Protocol........................................................................................... Page 35 Document1 Page 191 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Brain cancer/metastases .................................................................... Page 57,183 Breakthrough dose ...................................................... Page 124,126,134,136,145 Breathlessness .................................................................................(see dyspnea) Buccal...................................................................................................... Page 133 Bupivacaine ............................................................................................... Page 40 Buproprion................................................................................................. Page 61 Buscopan..................................................................................... page 17,103,141 C Cachexia........................................................................................ Page 81,83,113 Calcitonin............................................................................................ Page 96,140 Calcium,corrected...................................................................................... Page 93 Cannabis ................................................................................................. Page 154 Capsaicin................................................................................................. Page 141 Carbamazepine ........................................................................... Page 90,141,154 CHF ................................................................................................. Page 23,38,66 Chlorpromazine ...................................................................... Page 54,90,109,141 Cirrhosis .................................................................................................... Page 23 Citalopram ................................................................................................. Page 60 Clodronate.......................................................................................... Page 96,140 Clonazepam .................................................................................... Page 141,187 Coanalgesics ..................................................................(see adjuvant analgesics) Codeine ......................................................................................... Page 33,39,138 Confusion ........................................................................................ (see delerium) Constipation.......................................................................... Page 26,101,115,133 COPD .............................................................................................. Page 38,64,66 Corticosteroids................. Page 39,54,58,68,83,96,103,109,117,140,179,182,188 Cough................................................................................................. Page 36,182 Cyproheptadine ....................................................................................... Page 117 D Death Rattle............................................................................................. Page 168 Decadron..............................................................................(see dexamethasone) Dehydration .................................................................................... (see hydration) Delerium ................................................................................. Page 44,48,115,133 Dependence ............................................................................................ Page 125 Depression .................................................................................... Page 19,56,115 Desipramine ................................................................................ Page 62,141,155 Dexamethasone ..................................................................... (see corticosteroids) Dextroamphetamine .................................................................................. Page 61 Dextromethorphan.............................................................................. Page 39,141 Diarrhea......................................................................................... Page 26,43,101 Diazepam ......................................................................................... Page 155,187 Dilantin ...........................................................................................(see phenytoin) Dimenhydrinate ....................................................................................... Page 109 Diuretics................................................................................................ Page 24,84 Document1 Page 192 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Docusate .............................................................................................. Page 31,32 Domperidone ........................................................................................... Page 109 Doxepin ..................................................................................................... Page 62 Dronabinol ........................................................................................ Page 109,117 Dry Mouth .....................................................................................(see xerostomia) Duragesic patch.................................................................................(see fentanyl) Dyesthetic pain ........................................................................................ Page 122 Dysphagia............................................................................ Page 16,115,116, 182 Dyspnea ....................................................................................... Page 17, 64,182 E ECOG ........................................................................................................ Page 88 Edema ........................................................................................... Page 44,98,182 Effusions............................................................................................... Page 38,66 EMLA............................................................................................... (see lidocaine) Enteral Feeding ........................................................................... Page 16,115,116 Epidural ............................................................................................ Page 133,142 Equianalgesia .............................................................. Page 129130,145,152,161 Exsanguination .......................................................................................... Page 75 F Fatigue .......................................................................................... Page 66,79,101 Fentanyl.............................................................................. Page 131,135,144,155 Fluoxetine........................................................................................... Page 60,155 Furosemide.......................................................................................(see diuretics) G Gabapentin.................................................................................. Page 90,141,188 Glycopyrrolate .................................................................................... Page 17,169 Granisetron.............................................................................................. Page 109 Guafenesin ........................................................................................... Page 18,39 H Hallucinations ............................................................................................ Page 50 Haloperidol ......................................................................................... Page 54,109 Hemmorhage.........................................................................(see Exsanguination) Hemoptysis................................................................................................ Page 76 Heparin.................................................................................................... Page 179 Hiccups...................................................................................................... Page 89 Home Oxygen Application ......................................................................... Page 72 Hydration ............................................................... Page 4146,53,94,102,168,187 Hydroxyzine............................................................................................... Page 18 Hyoscine Butylbromide.................................................................. (see Buscopan) Hyoscine Hydrobromide ........................................................... (see Scopolamine) Hypercalcemia...................................................................................... Page 43,91 Hypodermoclysis ................................................................................ Page 45,116 I Document1 Page 193 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Imipramine.......................................................................................... Page 62,155 Incident Pain..................................................................................... Page 131,164 Itching................................................................................................. (see pruritis) J K L Ketamine ................................................................................................. Page 141 Lactulose ......................................................................................... (see laxatives) Lancinating pain ...................................................................................... Page 122 Laxatives .........................................................................................Page 3132,35 Lidocaine ............................................................................................ Page 40,141 Loperamide................................................................................................ Page 33 Lorazepam..................................................................... Page 54,109,187,188,189 Lou Gehrig’s disease..................................... ( see Amyotrophic Lateral Sclerosis) Lymphoedema........................................................................................... Page 98 Lyrica............................................................................................ (see pregabalin) M Malignant Bowel Obstruction ......................................................... Page 43,99,115 Massage ......................................................................... Page 60,67,83,89,98,137 Maxeran ...............................................................................(see metoclopramide) Megestrol acetate .................................................................................... Page 117 Melatonin................................................................................................. Page 117 Meperidine........................................................................................ Page 126,155 Methadone............................................................................ Page 39,131,141,149 Methotrimeprazine.................................................................. Page 54,68,109,141 Methylphenidate ................................................................................. Page 61,155 Metoclopramide ............................................................... Page 32,90,103,108,116 Metoprolol.................................................................................................. Page 18 Metronidazole ..................................................................................... Page 33,155 Mexelitine ................................................................................................ Page 141 Midazolam .......................................................................................... Page 90,187 Mirtazapine ................................................................................................ Page 61 Motilium .................................................................................... (see domperidone) Mouth Care.................................................................................. Page 43,102,168 Multiple Myeloma....................................................................................... Page 94 Muscle Spasm ......................................................................................... Page 141 Music Therapy.................................................................................... Page 67,137 Myoclonus ....................................................................................... (see twitching) Myopathy ................................................................................................... Page 81 N Nabilone .................................................................................................. Page 109 Nausea and Vomiting Chart..................................................................... Page 112 Nausea and Vomitting ................................................... Page 43,105,112,115,133 Nerve Blocks ........................................................................................... Page 142 Nerve Compression................................................................................. Page 141 Document1 Page 194 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Nerve Injury ............................................................................................. Page 141 Neuropathic Pain ....................................................................... Page 122,141,150 Nitrous Oxide........................................................................................... Page 141 NMDA receptor................................................................................. Page 141,149 Nociceptive Pain ..................................................................................... Page 122 Nortriptyline ........................................................................................ Page 62,141 Nozinan ............................................................................(see methotrimeprazine) NSAIDs................................................................................. Page 18,117,138,140 Nutrition ................................................................................................... Page 113 O Octreotide................................................................. Page 25,33,103,108,109,155 Olanzapine .............................................................................................. Page 109 Omega 3 fatty acids................................................................................. Page 117 Ondansetron............................................................................................ Page 109 Opioid Neurotoxicity .......................................... Page 44,54,134,136,150,186187 Opioid Rotation.......................................................................... Page 136,145,152 Opioid Titration ................................................................................. Page 134,147 Opioid Withdrawal ................................................................................... Page 136 Opioids ...................................... Page 31,39,54,68,124,126,129,132136,141,179 Opioids, nebulized ..................................................................................... Page 68 Opioids, long acting ................................................................................. Page 135 Oxygen ................................................................................ Page 18,69,72,74,187 P Pain Assessment..................................................................................... Page 119 Pain Management ................................................................................... Page 124 Palliative Sedation .............................................................................. Page 55,171 Pamidronate ....................................................................................... Page 95,140 Paracentesis.................................................................................... Page 22,24,66 Paroxetine ................................................................................................. Page 60 Phenobarbital ................................................................................... Page 188,189 Phenytoin............................................................................ Page 141,188,189,155 Physiotherapy.................................................................... Page 19,67,98,108,137 PostHerpetic Neuralgia pain................................................................... Page 141 PostMastectomy pain ............................................................................. Page 141 PPS ........................................................................................................... Page 85 Pregabalin ............................................................................................... Page 141 Prochlorperazine ..................................................................................... Page 109 Promethazine .......................................................................................... Page 109 Propranolol ........................................................................................... Page 18,58 Pruritis ..................................................................................................... Page 133 Psychosocial Care........... Page 16,5253,5860,67,108,115,119,122,127,173,179 Q R Radiation ......................................................................page 101,107,142,178,182 Document1 Page 195 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · · Radicular Pain ......................................................................................... Page 176 Raised Intracranial Pressure ................................................................... Page 141 Rectal Spasm .......................................................................................... Page 141 Respiratory Congestion ............................................... (see respiratory secretions) Respiratory Depression .................................................................... Page 134,153 Respiratory Distress .................................................................................. Page 69 Respiratory Secretions ....................................................................... Page 44,166 Restlessness ...................................................................................... Page 48,133 Riluzole...................................................................................................... Page 14 S Scopolamine................................................................................ Page 17,109,169 Sedation ........................................................................................... Page 133,171 Seizure ............................................................................................. Page 162,183 Sennosides...................................................................................... (see laxatives) Sensory Disturbances ...................................................................... Page 122,176 Sertraline ............................................................................................ Page 60,155 Shortness of Breath Patient Handout ...................................................Page 7374 Shortness of Breath......................................................................... (see Dyspnea) Sialorrhea .................................................................................................. Page 17 Sleep hygiene.......................................................................................... Page 186 Sodium Cromoglycate ............................................................................... Page 40 Somatic Pain ........................................................................................... Page 122 Spinal Cord Compression................................................................... Page 81,174 Spiritual Care........................................................................ Page 16,108,119,181 Spirololactone...................................................................................(see diuretics) Steady State ............................................................................................ Page 124 Stemetil ...............................................................................(see prochlorperazine) Sufentanil.......................................................................................... Page 131,164 Sundowning effect............................................................................... Page 53,54 Superior Vena Cava Obstruction ................................................... Page 38,66,182 SVC ............................................................(see Superior Vena Cava Obstruction) Syncope .................................................................................................. Page 134 T TCA .................................................................................................... Page 62,141 Tenesmoid pain ......................................................................... (see rectal spasm) Terminal Secretions..................................................... (see respiratory secretions) Therapeutic touch................................................................................. Page 60,67 Tizanidine .................................................................................................. Page 19 Topical.............................................................................................. Page 133,141 Torsades de Pointes......................................................................... Page 149,157 Total Pain ........................................................................................... Page 14,119 TPN (Total Parenteral Nutrition) ....................................................... Page 102,116 Tramadol ................................................................................... Page 131,155,160 Transderm V.............................................................................. (see scopolamine) Document1 Page 196 of 197 nd Hospice Palliative Care Symptom Guidelines 2 Edition · · · · · · · · · · · · · · Trazadone ................................................................................................. Page 61 Tremors ..................................................................................................... Page 50 Twitching .......................................................................................... Page 134,183 U V W X Y Z Urinary Retention........................................................................... Page 33,52,176 ValproicAcid............................................................................... Page 141,187,189 Venlafaxine................................................................................................ Page 61 VisceralPain............................................................................................. Page 122 W.H.O principles...................................................................................... Page 128 Weakness.................................................................................... Page 79,101,176 Xerostomia ....................................................................................... Page 115,134 Zofran ........................................................................................ (see ondansetron) Zoledronic Acid................................................................................... Page 96,140 Zometa .................................................................................. (see zoledronic acid) Zostrix............................................................................................. (see capsaicin) Document1 Page 197 of 197
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