Introduction to Management of Common Symptoms: “Death I understand very well, it is suffering that I cannot understand.” Pain and Nausea John A. Mulder, MD -- Isaac C. Singer Vice President, Medical Services Faith Hospice Grand Rapids, MI Medical Director of Palliative Care Services MetroHealth "Not to relieve pain optimally is tantamount to moral and legal malpractice." -- Dr. Edmund D. Pellegrino Barriers to Pain Control Definition of Pain: “Pain is whatever the experiencing person says it is, existing whenever he/she says it does.” -- M. McCaffery, RN, MS, FAAN • • • • • • Inadequate assessment Inadequate pain reporting Reluctance to take opioids Reluctance to prescribe opioids Nurses reluctant to give opioids Excessive regulation 78% 62% 62% 61% 52% 36% Roenn, Ann Intern Med, 1993 1 Pharmacologic Treatment of Pain “No patient should ever wish for death because of a physician’s reluctance to use adequate amounts of effective opioids.” -- Jerome H. Jaffe • Select the appropriate analgesic drug • Prescribe the appropriate dose • Administer the drug by the appropriate route • Schedule the appropriate dosing interval • Prevent persistent pain and relieve breakthrough pain (Goodman and Gilman, 1990) Pharmacologic Treatment of Pain Pharmacologic Treatment of Pain • Titrate the dose of the analgesic aggressively • Cornerstone of cancer pain management • Prevent, anticipate, and manage side effects • Must be individualized • Consider sequential trials of opioid analgesics • Should be as simple and as non-invasive as possible • Use appropriate co-analgesic drugs • Equianalgesic tables must be used • Addiction and tolerance to opioid analgesics are rare WHO Ladder Step 1 Non-Opioid Analgesic Drugs Opioid for moderate to severe pain  Non - opioid  Adjuvant Non - opioid  Adjuvant PAIN • Limited value in advanced pain due to low maximal efficiency • Acetaminophen Opioid for mild to moderate pain + Non - opioid  Adjuvant 3 2 • Non-steroidal anti-inflammatory drugs (NSAIDs) 1 2 Step 2 Opioids for Moderate Pain Step 2 Opioids for Moderate Pain Limited to treatment of mild to moderate pain Analgesic • Dose-limiting side effects Codeine 100 50 Hydrocodone 15 N/A 7.5-10 N/A • Fixed combinations with acetaminophen or aspirin Oxycodone Oral Dose (mg) Parenteral Dose (mg) * Not recommended for routine use: propoxyphene (long half-life, toxic metabolite) Codeine (Tylenol w/Codeine # 2, 3, 4) (Anexia, Hycodan, Lorcet, Norace, Vicodin, Zydone) Dose ceiling: 1.5 mg/kg (90-120 mg) • Dysphoria • Nausea • Constipation Upward dose titration limited by fixed combination with acetaminophen. (Combination products: DEA Schedule III) Oxycodone Hydrocodone (Percocet, Percodan, Tylox) Overlap opioid: Step 2 and Step 3 Fixed combination products • Frequently prescribed for moderate to severe pain • Upward dose titration limited by fixed combination with acetaminophen or aspirin • Combination products: DEA Schedule II • Less toxic than codeine • Upward does titration limited by fixed combination with acetaminophen • Combination products: DEA Schedule III Basic Rules for Narcotic Administration • Use oral formulations if possible • Principle of opioid monotherapy • Start with immediate release formulations in patients with significant pain • Use medications around-the-clock for constant pain (fixed dosing) 3 Basic Rules for Narcotic Administration • Goal: Controlled Pain (4 or fewer rescues) • Dose Escalation: Quickly until controlled pain • Maximum Dose: Does not exist • Side Effects: – Accommodation in 7-10 days – Treat aggressively – Bowel regimen Morphine (MS Contin, MSIR, Roxanol, Avinza, Kadian) • Most commonly used Step 3 opioid • Multiple dosing forms Morphine sulfate in Contin delivery system Step 3 Opioids for Mod. to Severe Pain Analgesic Oral Dose Parenteral Dose (mg) (mg) Morphine 15 5 Oxycodone 10 N/A Hydromorphone Fentanyl 4 1.5 25 mcg/h q 72 h 25 mcg Oxycodone (OxyContin, OxyFast, OxyIR, Roxicodone) Oxycodone in AcroContin delivery system Should not be cut, crushed, or chewed • No apparent dose ceiling • May be less toxic than morphine Should not be cut, crushed, or chewed Hydromorphone (Dilaudid) • Oral use hampered by lack of controlled-release formulations Transdermal Fentanyl (Duragesic) • Patch Size: 12.5, 25, 50, 75 and 100 mcg • Duration of Action: 72 hours • Advantages: • Easy, convenient use • No need to remember to take meds • Disadvantages: • Difficult when using high dose of narcotics • Thin patients with little subcutaneous tissue 4 Fentanyl Patch Indications • • • • Patients unable to take oral medications Non-compliant patients Question of drug abuse Question of cognition Titration Schema Transmucosal Fentanyl (Fentora, Actiq) • Strengths (Fentora): 100, 200, 300, 400, 600, 800 mcg • Advantages: • Rapid onset • Easy to use • Can be used in patients who cannot swallow Narcotic Equivalence Initial Fixed and Rescue Dose • 10 mg Morphine = 2.5 mg Hydromorphone = 10 mg Hydrocodone = 7.5 mg Oxycodone = Controlled Pain 100 mg Meperidine = 120 mg Codeine Moderate Pain Severe Pain • 1 mg sc/im/iv = 3 mg po • 100 mg/d Morphine = 50 mcg/h Fentanyl/72h No Change 25% Increase 50% Increase Unwarranted / Exaggerated Fears • Respiratory Depression Prescribe the Appropriate Dose • Addiction • Based upon pain intensity and current analgesic therapy • Rapid Tolerance • No one optimal dose • Regulatory Reprisal • No one maximal dose • Appropriate dose: pain relief throughout dosing interval without unmanageable side effects 5 Schedule the Appropriate Dosing Interval • Prevent pain recurrence • Minimize number of daily doses • Depends on opioid and route • End-of-dose failure: • Increase dose • Keep same interval Notable Quotes Famous Vomiting in Literature "One of the best temporary cures for pride and affectation is seasickness; a man who wants to vomit never puts on airs.” Josh Billings 1860 "The act of vomiting deserves your respect. It's an orchestral event of the gut.” Mary Roach, Packing for Mars: The Curious Science of Life in the Void "Oh, my God! I'm gagging and vomiting at the same time. I'm... I'm gavomiting!" Dr. Cox, Scrubs Famous Vomiting in Politics "As a dog returneth to his vomit, so doth a fool return to his folly." Proverbs Famous Vomiting in Sports 6 Historical Remedies Vomiting in Pop Culture Bloodletting Ginger Mint Frankincense Etiology of Nausea 1) Chemoreceptor Trigger Zone 2) Vestibular 3) Cortex 4) GI/peripheral pathways Identify Potential Reversible Causes * Drugs (chemo, opioids, abx, NSAIDS, SSRIs) * Constipation * Gastroparesis * GERD * Uremia * Pain * Infection * Dehydration * Electrolyte imbalance (high Ca) * Endocrine dysfunction * Increased ICP * Anxiety Assessment Onset Frequency Relationship to eating Relationship to meds Current anti-emetics Chronic vs. Progressing Alleviating factors Severity (scale: 1-10) Goal Other Causes * Pregnancy * Cyclic Vomiting Syndrome * Hepatic disease * Migraine headaches * Following surgery * Myocardial infarction * Violent coughing * Hangover * Meniere's disease 7 • Most patients have multi-factorial causes Non Pharmacologic Treatment Non-pharmacologic Treatment * Correct dehydration, electrolyte disturbances * Reassurance/relaxation • * Constipation regimen • * Decompress Non-pharmacologic Treatment * Oral hygiene * Decrease portions, use cold food * Decrease or cease tube feedings Non-pharmacologic Treatment * Avoid odors 8 Matching Etiology with Mechanism Matching Medication to Mechanism D2 Antagonists: Haldol, Reglan, Compazine, Thorazine 1) Chemoreceptor Trigger Zone 2) Vestibular 3) Cortex 4) GI/peripheral pathways 1) D2 and 5HT3 antagonists 2) Antihistamines and Anti-muscarinics 3) Antihistamines and Anxiolytics 4) D2 and 5HT3 antagonists 5HT3 Antagonists: Zofran, Emend, Remeron Anti-histamines: Benadryl, Phenergan, Antivert, Cyclizine Anti-cholinergics/anti-muscarinics : Hyoscyamine, Scopolamine Pro-motility: Reglan, Propulsid Others: Decadron, Ativan Opioid-Induced Chemotherapy-Induced • Primarily hits CTZ Consider opioid-rotation Think D2 Antagonist: Reglan, Haldol, Compazine, Thorazine Malignant Bowel Obstruction Primarily from stimulation of CTZ • Primarily from 5HT3 stimulating gut/peripheral pathways Think 5HT3 antagonists: Zofran, Emend, Remeron Motion-Induced Primarily from stimulation of vestibular system Think D2-antagonist: Reglan, Haldol Think anti-muscarinics: Scopolamine, Hyoscyamine Don't forget to decompress Think anti-histamines: Antivert, Phenergan Remember Decadron 9 Increased ICP Most patients have multi-factorial causes Directly stimulates the Vomiting Center Steroids act to decrease pressure Think anti-histamines Dosing Intractable Vomiting • "Go hard or go home" Appropriate doses... scheduled around-the-clock Poly-Drug Regimens and Routes of Delivery ABHR (Ativan, Benadryl, Haldol, Reglan) General guidelines: Can be given topically, orally or rectally * Avoid use of more than one drug from each class * Consider less traditional medications: Decadron, Ativan But does it work? * May need to consider alternate routes: topical, rectal, SQ * Be alert for drug interactions 10 Continuous Infusions • Have the potential to provide very quick and effective relief of intractable nausea Acupuncture / Acupressure In nausea, stimulation of point MH6 (forearm) is believed to offer relief. Benadryl/Ativan/Decadron (BAD drip): (0.2-2.0 ml/hr) (50 cc D5W, 200 mg Benadryl, 8 mg Ativan, 20 mg Decadron) Reglan/Benadryl/Decadron (RBD drip): (0.5-1.5 ml/hr) (50 cc NS, 80 mg Reglan, 100 mg Benadryl, 8 mg Decadron) Could consider Haldol/Ativan/Decadron, or Reglan/Ativan/Decadron Non-traditional Meds Marijuana Bendectin (pyridoxine/doxylamine) Anti-histamine, sedating NO evidence of causing birth defects Propulsid (cisapride) 5HT4 Agonist Prolonged QT Available only for "compassionate use" • Active ingredient: Nine-delta-tetrahydrocannabinol (THC) Demonstrated effectiveness in: Amelioration of nausea and vomiting Inducement of hunger in settings of chemotherapy and AIDS Analgesia Lowering intra-occular pressure ? Multiple Sclerosis ? Depression Ginger lollipops Legal Issues: • Michigan Law vs. FDA On Dec.4, 2008, the Michigan Medical Marihuana Act was enacted into law allowing patients with debilitating medical conditions such as HIV, cancer, and Hepatitis C to legally possess and use marijuana.[69]The patient can have up to two and a half ounces of usable marijuana and twelve plants that are kept in an enclosed and locked facility.[70] Tetrahydrocannabinol Dronabinol (Marinol) - a Schedule III drug Nabilone (Casemet) - a Schedule II drug available in Canada Sativex (THC + canabidiol) mouth spray for M.S. patients Cannabis is classified as a Schedule I drug under the federal Controlled Substances Act of 1970 and is deemed to have a high potential for abuse and no legitimate medical uses 11 Random Thoughts Successful Strategies * Reglan (metoclpramide) 1st drug of choice: has GI effects and CTZ effects Attempt to identify the most likely etiology and mechanism involved * Haldol is a great anti-emetic Choose the medication based on that mechanism * Steroids too Dose appropriately and on a scheduled basis * NG tube may be necessary * Combination drugs of different mechanisms may be helpful * Anticipatory dosing most beneficial * Use of 5-HT3 antagonists of questionable benefit in non-chemotherapy-induce N/V If ineffective, consider multi-drug regimens Consider continuous infusions (RBD, BAD) Consider less traditional interventions/medications John Mulder, MD 616-293-3615 [email protected] http://palliativematters.blogspot.com 12