Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Management of Pain in Cancer Patient Dr. Khaled Abulkhair, PhD Medical Oncology SCE, Royal College, UK Ass. Professor of Clinical Oncology Mansoura University, Egypt Purpose • Review • • basic principles of pain management and analgesic therapy in cancer patients. Case study illustrating common pain problems and suggested management. Self evaluation Pain in Cancer Patients What is pain? • An unpleasant feeling occurring as a result of injury or • • disease, usually localized in some part of the body. Bodily suffering characterized by such feelings. Mental or emotional suffering; distress. Incidence: • 30-40% of patients at time of diagnosis or during • disease -modifying treatment. 70- 90% in those with advanced disease. Pain is unpleasant sensation! Yet protective 4 Unlike other types of pain! Severe, sharp and short In healthy people Severe, Sharp, chronic in unhealthy patient 5 Pain in Cancer Patients Aetiology • Direct tumour involvement: 62-78% • As a result of diagnostic or therapeutic interventions 19-25% – Post- radiation ( enteritis; nerve injury; osteonecrosis) – Post-chemotherapy ( e.g. mucositis; peripheral neuropathy) – Post- operative pain- acute and chronic • Cancer induced syndromes <10% – Constipation, pressure sores, shingles • Pain unrelated to malignancy or treatment 3-10% Direct Invasion by Cancer 7 Large Lytic Metastases 8 Bed Sores 9 Types of Pain • Acute: e.g. procedural pain; pathological fracture; bowel/ureteric obstruction • Chronic • Acute on Chronic (Breakthrough pain) • Malignant; Non-Malignant Types of Pain • Nociceptive: Direct response to tissue injury Includes musculoskeletal (somatic) and visceral pain • Neuropathic: Pain associated with damage to the nervous system • Mixed pain syndromes Untreated Pain….. Patients and caregivers need to understand that pain is important. There is an urgency. If pain is not controlled, their lives are out of control. Impact on • Function • Sleep • Impaired cognitive function • Quality of life Outcomes • Depression • Decreased socialization • Increased health care utilization • Increased costs 12 “Pain is a more terrible lord of mankind than even death itself ” Albert Schweitzer 13 Outcome of cancer Pain Management There’s more to cancer care than simply helping patients survive. There's more to cancer treatment than simple survival. - > 80% will achieve good control - 15% will have fair control - < 5% will have poor or no control Principles of Cancer Pain Management • Start early…… • The most important step in treating pain is the • • • assessment. Oral route is preferred when available. Although the ratio of oral to parenteral morphine is commonly noted to be 6:1, clinical observation of chronic cases indicates that this ratio is closer to 3:1. Choose the analgesic drug and dose to match the degree of pain suffered by the patient. Before adding or changing to another drug, maximize the dose and schedule of the current analgesic drug. 15 • For persistent severe pain, use a product with a long • • • • duration of action. Pain medications should always be administered on a scheduled basis or around the clock. It is always easier to prevent pain from recurring than to treat it once it has recurred. As-needed dosing should be used for breakthrough pain. If more than two as-needed doses are required for breakthrough pain in a 24-hour period, consider modifying the regimen. Provide medications to prevent adverse events such as constipation and itching. Use appropriate adjuvant analgesics and nondrug measures to maximize pain control. 16 Abdou • 83 year old widower: Lives alone • Ca Prostate with Bony metastases; Hx OA/ IHD/ Depression • Brought in by daughter: Won’t leave the house • Increased pain in his shoulder and lower back for 2 weeks • Constipated 17 Pain Assessment Tools • Listen carefully: What are the words used? May deny pain but will admit to having “discomfort”, “aching” or “soreness” Do you hurt anywhere? Are you uncomfortable? How does it affect you? • Because pain is subjective, it is best evaluated by the • patient (i.e., not a caregiver and not the health professional). Believe the patient “pain is what the patient says hurts….the best judge of a patient’s pain is the patient” Bonica. 18 OPQRSTUV O NSET: When did it start? P ATTERN: How often; When; How long? Q UALITY: Describe it: sharp, dull...Colic R ELIEVING/AGGRAVATING FACTORS S EVERITY: Scale of 1- 10 T REATMENTS: What helps; For how long U NDERSTANDING: What do you think is causing it?. How does it affect you? V ALUES: Goals Of Care; expectations 19 Tools Please rate your pain by circling the one number that best describes your pain _____________________________________________________________ 0 1 2 3 4 5 6 7 8 9 10 What is your Pain at it’s Best / Worst/ Present/ Average No Pain Pain as bad as you can imagine In the past 24 hours, how much RELIEF have pain treatments or medications provided? Please circle the one percentage that most shows how much. _____________________________________________________________ 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% 20 Pain History: Abdou • O(nset): Several months/ 2 weeks • P(attern): R shoulder/lower back pain. Constant. • • • • • Increased with movement (what would be named?). Q(uality): Steady aching pain R(elief): Medication helps for about 2-3 hrs S(everity): 6/10. 10/10 with movement T(reatments): T#3 helps for about 2-3 hours. Takes about 12-15 T#3 a day U(nderstanding): Not going on any Morphine. I’m not dead yet. 21 Examination • No evidence of fractures but clearly limited ROM in the shoulder due to pain • No vertebral tenderness and no neurological signs • Bowel and bladder function normal…yet constipated • X-rays show bony mets. in shoulder and lumber spine 22 Abdou– approach to treatment Develop a problem list to resolve Somatic / bone pain Acetaminophen dosing too high (~4 Gm) Constipation contributing to pain intensity Compliance issues 23 • Do not under-estimate the patient’s condition based on his denial. 24 25 How would you better manage Abdou’s pain? DRUGS 26 Pain Management is not only drugs Educate patient and family: - Myth: “Save it for ..when it gets worse” • FACT: Treating early prevents pain • FACT: No ceiling effect of strong opioids - Myth: “I’ll become addicted” • FACT: Addiction is rare. Boston study- 0.03% • FACT: Tolerance is rare in Palliative Patients/PO route. - Myth: Treatment worse than pain • FACT: Side effects can be managed/treated 27 Education Constant pain requires regular dosing Avoid peaks of pain as with prn dosing Smoother blood levels can provide more consistent pain control More convenient Less analgesia over time Maintain uninterrupted sleep 28 Morphine WHO 3-step Ladder Hydromorphone Methadone Fentanyl Oxycodone ± Adjuvants Codeine Oxycodone ± Adjuvants Acetaminophen NSAIDs ± Adjuvants 29 Drugs for Pain Management Acetaminophen NSAIDS Opioids Adjuvants/ Co analgesics A. Bisphosphonates/Calcitonin B. Antidepressants C. Anti-convulsants D. Disease specific therapies: Radiation/Chemotherapy/Surgery E. Steroids 30 Analgesics • Step 1: Mild pain: – Acetaminophen: Max 2.4 gm/day Can be very effective for mild-moderate pain if given regularly…caution with Hepatic patients. – NSAIDs: Issues re GI and renal toxicity Concerns in the elderly... Non-specific: Use with GI protection COX 2 agents safer re GI morbidity and antiplatelet effects 31 NSAIDS • Both peripheral and central effects • Inhibit cyclo-oxygenase (COX) enzyme -> Decreased prostaglandin production • Specific COX 2 inhibitors: Celecoxib, rofecoxib. Less GI effects • Less effect on platelet function “Non-Selective” COX 2 inhibitors: Diclofenac Nonacetylated salicylates: Diflunisal 32 NSAIDs • Ibuprofen Q4-6h, Max 2400 mg/day • Diclofenac Potassium, Cataflam, Q 8-12h, Max 150 • • • • • • mg/day…first day 200 mg. Diclofenac Sodium, Voltaren, Q 8-12h, 150 mg/day. Indomethacin Q8-12h, Max 200 / day Naproxyn Q 12h, max1650 mg/day Meloxicam Q24h, Max 15mg/day Tenoxicam, Epicotel, Q24h, max 20 mg Celecoxib Q12h, Max 400mg/day 33 Step 2 + 3 Opioid Use Opioids help relieve moderate to severe pain ( and dyspnea in terminal patients). Opioid receptors have been targeted for the treatment of pain and related disorders for thousands of years. they produce analgesia primarily by inhibiting nociceptive transmission in the central nervous system Episodic pain - Prescribe as needed Constant pain = Regular dosing PLUS a “breakthrough” PRN dose Right drug at the Right dose 34 Step 2: Moderate pain Tramadol…PO, IV … • variable responses… • Max…400 mg/day • Constipation and mode changes • Myths 35 Codeine…..Co Weak Opioid About 10% of population lack enzyme to convert to Morphine Ceiling effect: > 600 mg/day Very constipating Combination product or alone Helpful for persistent pathological cough. 1:10 ( Morphine : Codeine) Sustained release preparation : Codeine Contin 50,100,150, 200 mg 36 Oxycodone: Moderate ->Strong Opioid • • • • • • • • • Active at the mu and kappa receptors Safe with decreased renal function Potency Oxycodone 1.5 - 2 :1 Morphine Less constipating than Codeine Lasts ~ 4-5 hours No ceiling effect/help Neuropathic pain Alone or with ASA/Acetaminophen OxyContin 10, 20, 40, 80 mg Start slow stop slow 37 Strong Opioids • Morphine still is the gold standard – Concerns re: metabolites in renal failure; elderly….Liver impairment. –Extensive first pass metabolism • Hydromorphone: – More soluble. – Few metabolites – 5x more potent than Morphine. Opioid Pharmacology • Cmax = 60 mins (after PO dose) • • 45 mins (after SC dose) 30 mins (after IM dose) 6 mins (after IV dose) t1/2 = 3-4 hours Duration = 20-24 hrs (immediate-release) 48-72 hrs (sustained-release) 39 Strong Opioids • Fentanyl: Not at mu receptor. More lipophilic – 100x more potent than Morphine. – Less constipation and nausea. – Less histamine release – Useful in true opioid allergy 40 Fentanyl • Transdermal Patch: different strengths in mcg/hour: 25 ~ 100 mg Morphine/day (45 -134) 50 ~ 200 mg (135-224), 75 (225-314), 100 ~ 400 mg (315-404 mg M/day) Takes ~17 hours to reach steady state Patch lasts 72 hours in 90% of patients • Sublingual, intranasal, subcutaneous, IV routes 41 Methadone • Semisynthetic used in maintenance treatment for opioid• • • • • dependent individuals as well as in patients taking opioids long term for moderate to severe pain Has activity not only at the opioid receptors, but also at the NMDA (N-methyl-d-aspartate) receptor Complex pharmacokinetics with extended half-life, which creates difficulties in dosing and transitioning from one opioid to another Associated with QT prolongation and/or torsades de pointes Effective long-acting agent; used for neuropathic pain Start low and titrate slowly. 42 Opioid Equi-analgesic Doses http://agencymeddirectors.wa.gov/mobile.html • 10 mg PO morphine =5 mg SQ/IV morphine (half the oral dose) = 100 mg PO codeine (1/10) = 2 mg PO Hydromorphone (1mg SQ) (5x more potent) = 5 - 7.5 mg PO Oxycodone ( 1.5x) = 0.5- 1 mg PO/pr methadone ( not Q4H) ( ~~10 x more potent) 43 Steps for converting between opioids • Calculate total mg dose taken in past 24-hours. • Determine equi-analgesic dose. • If pain is controlled on current opioid, reduce the • • • • new opioid daily dose by 25-50% to account for cross-tolerance, dosing ratio variation, and interpatient variability. If pain is uncontrolled on the current opioid, increase opioid daily dose by up to 100-125%. Titrate liberally and rapidly to analgesic effect during first 24 hours. Monitor for adverse events and effectiveness. Reassess the analgesic effect every 2-3 days. 44 Abdou Proposed Management Strategy? 45 Abdou • 12-15 T#3 = 350/30 mg not controlled – 3900- 4875 mg Acetaminophen plus – 360- 450 mg Codeine ~ 36- 45 mg PO Morphine TDD (total daily dose) ~ 7- 9 mg PO Hydromorphone ~ 25- 30 mg PO Oxycodone ~Patch? • Concerns re Acetaminophen dose/ Approaching ceiling Codeine 46 Abdou • Rotation to strong opioid: • Which one? • Dose: ? Equi-analgesic - ? Increase dose - BT (Break Through) 47 Opioid Adverse Effects • Constipation: “ The hand that writes the opioid prescription should start the laxative” ٠ Stimulant (+/- softener) (+/- osmotic) ٠ Nausea: ٠Approximately 50% will have some nausea in first week; 30% after that ٠In those prone to nausea consider anti-emetic (metoclopramide) 48 Abdou: 2 days later Morphine SR 30 mg BID = 60 mg PLUS 6 BT of 5 mg = 30mg 90mg • Increase to morphine SR 45 mg BID • BT: 10% of TDD or 1/2 of Q4H dose 49 Bone Pain What role would the following play? Radiotherapy NSAIDs steroids Bisphosphonates calcitonin What else might you do? Spiritual 50 Breakthrough Pain • End of dose pain: Usually requires dose increase regular medication • Paroxysmal/Idiopathic: Titrate to only 1-3 BT’s /day BTD should be 10% of TDD/1/2 of Q4H • Incident Pain Precipitant. Peaks early. Short duration 65% last 30 minutes or less 51 Ideal Analgesic Easily administered Rapid onset Short-duration of action In patient’s control Before the event 52 In Reality….Good and Bad Side Effects Expensive In-availability Tolerance Toxicity 53 Abdou: 3 months later • Confused , drowsy • Not eating • Pain on any weight bearing, despite recent • • RXT, radiating into his Left leg Some myoclonus LAB: Normal Calcium, Creatinine 2mg/dl 54 Abdou Current medication: ٠ morphine SR 100 mg PO BID ٠ Also taking about 5 BT of 20 mg/day. ٠ 200 mg plus 100 mg = 300 mg morphine TDD What do you recommend re his pain management? 55 Abdou …Problem list? Bone Pain with Incident Pain? Opioid toxicity? Neuropathic Pain? New mets to brain or liver? Constipation? 56 Opioid Toxicity….augmented by renal impairment Sedation Constipation Urine retention Nausea / vomiting Hyperalgesia Agitated delirium Myoclonus Respiratory depression 57 Opiate conversion: Knowing he was taking Morphine 300 mg /day. What dosage would you initiate the following with? – Hydromorphone? X 5 – Oxycodone? X 1.5 -2 58 Key learning - Give medication orally whenever possible. - less invasive, effective, convenient, cost effective analgesia. - rapid onset of action with oral formulations can be achieved with: IR opioids, certain controlled-release opioids (e.g. CR oxycodone or CR codeine) 59 REMS: Risk Evaluation and Mitigation Strategy for Extended-Release/LongActing Opioid Analgesics On June 9, 2012, the FDA announced it would require manufacturers of extendedrelease and long-acting opioid analgesics to provide training for health care professionals who prescribe these agents. 60 Adjuvant analgesics Drugs whose primary indication is other than pain; they are used to manage specific pain syndromes. Most often, adjuvant analgesics are used in addition to, rather than instead of, opioids. • Antidepressants • Transdermal lidocaine • Corticosteroids • Benzodiazepines • NSAIDs • Bisphosphanates 61 Bisphosphonates • Family of drugs that prevents bone • • • • resorption by inhibiting osteoclasts. Helpful in bone pains due to metastases. Best in use is zoledronic acid (zometa), given as 4 mg I.VI every 4 – 6 weeks. Renal impairment is an issue. Oral forms are available. Issues regarding GIT upsets and nephrotoxicity. 62 Radiation Therapy • Effective in palliating pain • • • • from bone mets, soft tissue masses. 60-70% Response rates. Different machines, energies and techniques. Can be re-challenged. Refer to a colleague 63 Neuropathic Pain • Pain that arises from injury, disease or dysfunction in the peripheral or central nervous system. • Incidence in Cancer : 30-50% • Usually described as burning, numbness, stitching or crushing. • Caused by (eg, trauma, ischemia, infections) or from ongoing metabolic or toxic diseases, infections, or structural disorders (eg, diabetes mellitus, amyloidosis, HIV infection, nerve entrapment, etc) which produce afferent impulses and signal damage to the nerve structures. 64 Herpes Reactivation 65 Treatment of Neuropathic Pain • Treat early as central mechanisms can cause persistence of pain • Adjuvant medications are essential • Titrate one medication at a time • Push dose until pain relief or intolerable side effects seen 66 Opioids in Neuropathic Pain Should always be tried Individual variation Methadone may be the most useful opioid in neuropathic pain Some evidence for oxycodone also being more useful 67 Antidepressants in Neuropathic Pain • Tricyclic antidepressants still the best Effective in 50-65% of cases • • • • • Nortriptyline = amitriptyline as first line Desipramine for those who don’t tolerate Starting dose 10 –25 mg Usual therapeutic dose is 50 –150mg Analgesic effect seen 4-7 days after reaching therapeutic dose • SSRI ..Escitalopram # Omeprazole 68 Anticonvulsants in Neuropathic Pain • Gabapentin … Try first • Gabapentin has good evidence for efficacy • Most respond to 2100 – 3600mg/day • Push dose to 6000mg/day 80%of patient can tolerate. • Pregabalin (Lyrica): • 75 -300 mg BID • Max 600 mg/day • Others: Carbamazepine; Clonazepam; Phenytoin 69 Miscellaneous Medications • Corticosteroids useful with associated swelling • • • • • and inflammation Baclofen if associated with muscle spasm Calcitonin 100-200 units/day helpful with phantom limb pain and sympathetically maintained pain ketamine Clonidine Mexiletine, flecanide, lidocaine 70 Self Evaluation Questions 71 1- A 75-year-old man has metastatic prostate cancer. The main sites of metastatic disease are regional lymph nodes and bone (several hip lesions). He experiences aching pain with occasional shooting pains. The latter are thought to be the result of nerve compression by enlarged lymph nodes. He has been taking oxycodone- APAP 5 mg 2 tablets every 4 hours and ibuprofen 400 mg every 8 hours. His current pain rating is 8/10, and he states that his pain cannot be controlled. Which is the best recommendation to manage his pain at this time? 72 A. Increase oxycodone-APAP to 7.5 mg/325 mg, 2 tablets every 4 hours. B. Increase oxycodone-APAP to 10 mg/325 mg, 2 tablets every 4 hours. C. Discontinue oxycodone-APAP, discontinue ibuprofen, and add morphine sustained release every 12 hours. D. Discontinue oxycodone-APAP, and add morphine sustained release every 12 hours. 73 2-Which is the most appropriate adjunctive medication for this patient’s pain? A. Naproxen. B. Single-agent (single ingredient) APAP. C. Gabapentin. D. Baclofen. 74 3- A 60-year-old man has head and neck cancer with extensive involvement of facial nerves. His pain medications include transdermal fentanyl 100 mcg/ hour every 72 hours and oral morphine solution 40 mg every 4 hours as needed. He is still having problems with neuropathic pain. Which treatment is best to recommend? A. Begin gabapentin and decrease the dose of fentanyl. B. Increase the doses of fentanyl and morphine. C. Begin diazepam and increase the dose of fentanyl. D. Begin gabapentin and continue fentanyl and morphine. 75 Summary: • • • • • • • • Comprehensive assessment is paramount. Avoid unnecessary delay in treating pain. Educate patient, family & caregivers. It is not a one man show. Use multi-disciplinary approach. Call your colleagues! Choose medications based on stepped approach, as well as side effect profile Tailor medication regimens to meet individual needs. Remember interactions and dose reductions in organ failures. Consider non-pharmacological options 76 77 References • Bruera E, Sweeney C. Methadone use in cancer patients • • • • • • with pain: a review. J of PM 5(1): 127-138, 2002 Bruera et al. A prospective open study of oral methadone in treatment of cancer pain. 9th World Congress on Pain, 2000 Lawlor PG, Turner KS, Hanson J, Bruera E. Dose ratio between morphine and methadone in patient with cancer pain - a retrospective study. Cancer 82(6): 1167-73, 1998 Ripamonti C. J Clinical Oncology, 1998 C Gannon. The Use of Methadone in the Care of the Dying, EJPC, 1997 R Fainsinger, T Schoeller, E Bruera. Methadone in the Management of Cancer Pain: A Review. Pain 52: 137-147, 1993 Bruera et al. Opioid Rotation in Patients with Cancer Pain. Cancer78(4): 852-857,1996 78