Mercy Hospital and Medical Center Management Guidelines for Adult Patients with Sickle Cell Pain Crisis 2011 (Adapted from the University of Chicago and Mercy Hospitals Sickle Cell Protocols) I. General Principles1: All patients need to be screened for complications of sickle cell disease at the time of admission. These include but are not limited to:  Acute chest syndrome (chest pain, new infiltrate on chest Xray, hypoxia)  Aplastic crisis  Multiorgan failure  Cerebrovascular events  Leg ulcers  Infections (bacteremia, pneumonia, etc.)  Priapism  Hepatic sequestration Assess the patient for possible causes of sickle cell pain crisis:  Dehydration  Hypoxia  Infection  Psychosocial stressors Laboratory Evaluation can not confirm or exclude the diagnosis of pain crisis, but is important to exclude life-threatening complications of the disease and/or identify reversible causes of a pain crisis (i.e. hypoxia, pneumonia, etc.) DVT Prophylaxis: No data currently exists as to whether sickle cell disease in and of itself increases the risk for venous thromboembolism (VTE) during hospitalization. However, increasing evidence suggests sickle cell disease is a prothrombotic condition. All patients should receive a risk assessment according to established guidelines in table below. All patients with risk factors should receive enoxaparin 40 mg subcutaneously daily or heparin 5000 unit subcutaneously Q 8hours in the absence of contraindications. Consider sequential compression devices (SCDs) in patients admitted with sickle cell disease without additional known risk factors for VTE. Major Risk Factors for VTE [Any one at admission warrants prophylaxis] Acute respiratory failure Heart Failure as admit diagnosis Age >70 years Malignancy/chemotherapy Acute stroke or myocardial infarction Major surgery in the past 30 days Critically ill Prior venous thromboembolism Known thrombophilia Central venous catheter (including peripherally inserted) Moderate RF for VTE [2 or more warrant prophylaxis] Obesity (>120 kg) Infectious disease as admit diagnosis Estrogen/oral contraceptive Chronic heart failure Age 40-70 years Nephrotic syndrome Acute inflammatory bowel disease as admit diagnosis Acute rheumatic disease as admit diagnosis Varicose veins Chronic lung disease Family history venous thromboembolism II. Inpatient Sickle Cell Pain Management A. Monitoring a. Chest X-ray: Order for any patient with cardiopulmonary complaints, hypoxia, know chronic lung disease, fever, tachycardia, or tachypnea. b. Complete blood count q24 hours c. c. Comprehensive metabolic panel, magnesium, phosphorous q48 hours  Keep magnesium level > 2 mg/dL: o Magnesium < 1.8 mg/dL, replace with IV magnesium rider  May need to follow with daily oral supplementation o Magnesium > 1.8 mg/dL, replace with oral product Lactic dehydrogenase (LDH) q72 hours B. Intravenous (IV) Fluid Management a. 0.45% NS IV b. Assess for dehydration. Replete, as needed. C. Incentive Spirometer D. Hydroxyurea: a. If patient is maintained on hydroxyurea at home, continue during hospital stay. b. In patient with evidence of significant or overwhelming infection, multiorgan failure or severe acute chest syndrome, hold hydroxyurea. E. Pain Management Principles a. Sickle cell pain is severe and incurable; treat using the same principles as for cancer pain. b. When using IV opioids, it is critical to REASSESS and ADJUST frequently. c. Scheduled IV Narcotic Dosing -- Opiate Naive Patients o Morphine sulfate: 0.1 mg/kg, usually 5 - 10mg, IV scheduled every 3-4 hours. (Patient may refuse dose, if not needed.) o Hydromorphone: 0.015 mg/kg, usually 0.75 - 2mg, IV scheduled every 3-4 hours. (Patient may refuse dose, if not needed.) o Monitor patient’s vital signs and pain level, using the pain scale, before and after every dose of pain medication administered. i. Mild: pain scale 1-3 ii. Moderate: pain scale 4-6 iii. Severe: pain scale 7-10 o Doses should be based on level of tolerance to opioids. Most adult patients with sickle cell disease have some opioid tolerance. Ask them what dose they usually require to relieve their pain or call the sickle cell care team. o IV bolus opioids will reach maximum analgesic effect within 10-15 minutes and will usually last 2-3 hours. Consider ordering around-the –clock (ATC) (patient may refuse) to ensure the patient is offered the medication consistently at the preferred interval. d. Scheduled IV Narcotic Dosing -- Opiate Tolerant patients o Convert the patients usual oral dose to IV: o MORPHINE IV/PO ratio: 1:3 o HYDROMORPHONE IV/PO ratio: 1:5 o EXAMPLE: Patient is taking morphine SR 60mg PO q12h and is now in pain crisis, requiring an additional 10mg PO q4 hours. 10mg X 6 = 60 mg + (60 mg x 2) = 180 mg PO morphine/day. Convert PO to IV: 180mg PO / 3 = 60mg IV over 24h = 10mg IV q4h o Start with 50-75% of the calculated equianalgesic dose if changing / converting to a different opioid to allow for incomplete cross-tolerance between opioids. o Use PRN doses to cover for break-through pain. e. PRN dosing should be ordered for q 1 or q 2 hours, to ensure patient’s pain is well controlled. f. Dose adjustment for pain o For mild-moderate pain: increase dose by 25 – 50 % o For moderate –severe pain: increase dose by 50 -100% g. Dose adjustment for taper o Decrease dose by 25% per day once the patient’s pain is under control for 24 hours h. Patient Controlled Analgesia (PCA) Principles—Used in the setting where scheduled IVP dosing is not controlling the patient’s pain. There is no “PCA protocol.” o General guidelines with specific suggestions for patients with sickle cell disease. i. Basal rates (i.e. continuous opioid infusion) should not be used in opioid naive patients until you have assessed their needs over a given period of time (i.e. after 12 hrs of demand/bolus doses) ii. Safety of the PCA lies in the fact that if the patient develops sedation, they will fall asleep and not continue pushing the demand button. Using a basal infusion rate in an opioid naive patient bypasses this safety mechanism. Only use a basal infusion rate in patients with a known opioid requirement. iii. In patients who are not opioid naive (those patients taking daily opioids), calculate an equianalgesic dose of currently used opioids over past 24 hrs and then convert to an equianalgesic basal rate (use the opioid conversion chart below). iv. Example: Patient taking 120 mg extended release morphine Q 12 hrs now in crisis taking an additional 15 mg immediate release morphine q 4 hrs. 15 mg X 6 = 90 mg + (120 mg X 2)= 330 mg PO morphine/day. Convert to IV equivalent 330/3= 110 mg IV morphine/24 hrs = 4-5 mg/hr. v. If changing/converting to a different opioid, start with 50-75% of the calculated equianalgesic dose to allow for incomplete cross-tolerance between opioids. vi. Example: To place patient above on hydromorphone PCA: 330 mg PO morphine/day = X mg IV hydromorphone/day 30 mg PO morphine______ 1.5 mg IV hydromorphone X = 16.5 mg IV hydromorphone/day / 24h = 0.7mg/h continuous infusion Start with 75% of calculated dose to adjust for incomplete cross-tolerance between opioids: 0.7(0.75) = 0.5 mg/hr continuous infusion. o o o PCA Bolus/Rescue/Demand Doses: i. Many recommend a PCA bolus dose of 50-150% of the basal infusion rate. ii. If the patient is not receiving a basal infusion, calculate your initial demand dose by considering the total amount of IVP medication it took to get their pain controlled in the first hour. iii. Example: Pt required a total of hydromorphone 6 mg IV to bring pain from severe to moderate in the first hour of presentation. Now receiving 6 mg IV Q2 hrs. Start with hydromorphone PCA with 2 mg demand dose available every 10 minutes. Goal is that the patient should not need to hit the button more than 1-2X’s/hour to achieve adequate relief. iv. IV breakthrough/bolus dose will reach peak effect within 10-15 minutes. Therefore, breakthrough/bolus doses on the PCA may be made available every 10-15 minutes. Titration of Opioids: i. Basal rate: In general, basal infusions will take at least 8 hours to reach steady state. Do not titrate the basal rate more frequently than every 8 hours. Use the number of bolus doses as a rough guide, but never increase basal rate by more than 100% at any one time. Demand Doses: Adjust demand dose size every 30-60 minutes to quickly reach adequate analgesia. i. For mild-moderate pain increase dose by 25-50%. ii. For moderate-severe pain increase dose by 50-100%. F. Converting to Oral Pain Management a. Once the IV dose has been tapered to 50% of the initial dose, start oral morphine or hydromorphone: o MORPHINE: Add total daily dose of IV morphine received; multiply by 2-3 to determine total daily dose. Immediate release formulations should be administered on a scheduled basis, every 4 hours. Sustained release formulations should be administered every 12 hours. Order the immediate release formulation every 4 hours PRN for breakthrough pain. The dose of immediate release morphine should be 25% of the 12-hour dose of MS Contin. o HYDROMORPHONE: Hydromorphone is not available as a sustained release formulation. i. Conversion of IV hydromorphone to oral: calculate the total daily dose received; multiply by 2-3 to determine the total daily oral dose. ii. The dose should be administered every 4 hours ATC. o OXYCODONE: include? i. Avoid acetaminophen-containing products, due to risk of acetaminophen toxicity. ii. Convert morphine or hydromorphone to an equianalgesic dose of oxycodone iii. Example: Convert morphine 10mg IVP q4h to oxycodone 30 mg PO q6h. May need to add additional oxycodone immediate release or change to sustained release formulation. b. Morphine is the preferred agent in treatment of sickle cell pain. True allergies to morphine are rare and include bronchospasm, angioedema and rash. G. Opioid Table H. Adjunct therapies a. Bowel regimen: All patients on opioids must also be on a bowel regimen of stool softener and a cathartic. b. May administer hydrOXYzine 25-50 mg PO with each narcotic dose. c. Itching: o In patients with history of itching, diphenhydramine 50mg IV/PO can be given with the initial dose of morphine and PRN for itching instead of hydrOXYzine. o Diphenhydramine may be given in conjunction with opiates for additive effect. d. Nausea: administer prochlorperazine 10mg PO PRN nausea. I. 4,5,6,7 Transfusion Principles a. Patients with SCD constitute the largest users of the national Rare Donor Registry in the US. Alloimmunization occurs in up to 30% of patients who receive frequent transfusions, likely because of ethnic differences between patients and blood donors. b. Iron overload is a significant problem in patients receiving multiple transfusions. Transfusions are indicated for specific clinical scenarios (see table below). c. Avoid blood transfusion for uncomplicated acute sickle cell pain crisis. With simple blood transfusion, the post-transfusion Hb level should not exceed 10-11 mg/dL to avoid hyperviscosity. d. Table--Clinical Indications for Transfusion: (Adapted from Lottenberg, R. Hematology 2005) Methods Conventional Indications Simple Transfusion Chronic Simple Transfusion Exchange Transfusion Symptomatic anemia Prevention of recurrent Stroke Recurrent acute chest syndrome or multi-organ failure Symptomatic anemia with Renal failure unresponsive to Epoetin Pulmonary hypertension or chronic hypoxia Acute neurologic event Recurrent debilitating pain Events Non-healing leg ulcers Acute priapism Acute chest syndrome Acute multi-organ failure Prep for major surgery Controversial Indications Acute splenic or hepatic Sequestration Prior to contrast media Severe ophthalmological complications Severe acute chest syndrome Preparation for major surgery Chronic use to avoid or reduce iron loading Recurrent priapism Selection of Blood Products: (Adapted from Lottenberg, R. Hematology 2005)  Sickle cell trait negative (for exchange)  Leukocyte reduced  Limited phenotype matching for all patients: ABO, C, D, E, and Kell antigens  Extended phenotype matching for patients with alloantibodies References: 1 Platt, A. Treating Sickle Cell Pain: An Update from the Georgia Comprehensive Sickle Cell Center. Journal of Emergency Nursing; 2002; 28(4): 297-303. 2 Pendleton, R. Venous Thromboembolism Prevention in the Acutely Ill Medical Patient: A Review of the Literature and Focus on Special Patient Populations. American Journal of Hematology; 2005; 79:229-237. 3 Telen, M. Principles and Problems of Transfusion in Sickle Cell Disease. Seminars in Hematology; 2001; 38(4): 315-323. 4 Lottenberg, R. An Evidence-Based Approach to the Treatment of Adults with Sickle Cell Disease. Hematology; 2005:58-65 5 Panchal, SJ. Cancer pain, National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology, version 1, 2004. http://www.nccn.org. 6 Ryan, M. As-Needed Morphine: Yes, but at What Dose and at What Interval? Journal of Clinical Oncology; 2005; 23(16) 3849-3852. 7 Emanuel LL, von Gunten CF, Ferris FD, ed. The Education for Physicians on End-of-life Care (EPEC) Curriculum. The Robert Wood Johnson Foundation, 1999. Fast Facts, National Residency End-of-Life Curriculum Project. www.eperc.mcw.edu.