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Pain Management in ESRD Alvin H. Moss, MD Section of Nephrology West Virginia University 1 Pain and ESRD Most common and severe symptom Impairs quality of life Undertreated in 75% of ESRD patients* Lack of knowledge in nephrology community *Davison SN. Pain in hemodialysis patients: Prevalence, cause, severity, and management. Am J Kidney Dis, 42:1239-1247, 2003 2 Objectives Demonstrate the importance of pain management within palliative care Present cases Document efficacy of WHO pain management approach in ESRD study Describe adverse effects of opioids Explain use of pain management principles 3 Association Between Reports of Symptoms and Quality of Life Measures 160 138 140 119 120 94.5 100 80 60 37.6 24.6 23.4 29 40 21.7 18.3 7.56.5 5.3 20 0 MQOL Total MQOL QOL Single SWLS Score Physical Item Index Subscale no symptoms 1 symptom 2+ symptoms Note: All results statistically significant, p values <.01 4 Causes of Pain in Hemodialysis Patients N=103/205* Cause Musculoskeletal Osteoarthritis Skeletal s Dx Osteoporosis RA, Bone Dis, Osteo Related to dialysis Peripheral Neuropathy Periph Vasc Disease Carpal tunnel Other * 19 > one type of pain. # Patients 65 20 19 12 14 14 13 10 2 19 Percent 63 19 19 12 14 14 13 10 2 19 Davison, AJKD 2003;42:1239-1247 5 A Role for Palliative Care The patient is an 87 yr old man with ESRD from hypertension who was admitted from a NH with altered mental status. The patient has been on dialysis for 4 years and is transported by ambulance for his treatments. Other medical problems include inoperable coronary artery disease, CVA with L hemiplegia, dementia, UGI bleeding, COPD, and PVD with gangrene of three toes on his right foot. He and his wife have refused surgery for the PVD. 6 A Role for Palliative Care The patient is unable to walk or transfer himself from chair to stretcher. He complains of severe pain in his right foot. He usually screams during dialysis and seems uncomfortable. The wife does not like him to receive pain medication because he becomes less responsive. What should be done? 7 What’s the problem? A 57 year-old dialysis patient is admitted with severe pain all over her body, especially in her joints. She has nephrogenic fibrosing dermopathy. Her current pain medicine is extended-release morphine 200mg po q8h. Despite this dose, she is still in pain. She also complains of increasingly severe jerking. It is so bad that her body jumps six inches off her chair at times. What’s going on and what should you do? 8 Patients’ Concerns Regarding End-of-Life Care Receiving adequate pain and symptom control Avoiding inappropriate prolongation of dying Achieving a sense of control Relieving burden on loved ones Strengthening relationships with loved ones Singer PA, et al. JAMA 1999; 281:163-168. 9 Top 5 Attributes of a Good Death Freedom from pain At peace with God Presence of family Mental awareness Treatment choices followed Steinhauser, et al. Factors considered important at the end of life by patients, family, physicians, and other health care providers. 10 JAMA 2000:284:2476-2482. Definition Palliative care is comprehensive, interdisciplinary care of patients and families facing a chronic or terminal illness focusing primarily on comfort and support. Billings JA. Palliative Care. Recent Advances. BMJ 2000:321:555-558. 11 Elements of Palliative Care Meticulous pain and symptom control Psychosocial and spiritual support Advance care planning incl goals of care Family-oriented care Delivery of coordinated services Attention to disposition 12 Nociceptive pain . . . Direct stimulation of intact nociceptors Transmission along normal nerves sharp, dull, aching, throbbing – somatic easy to describe, localize – visceral difficult to describe & localize 14 Neuropathic pain . . . Disordered peripheral or central nerves Compression, transection, infiltration, ischemia, metabolic injury Pain may exceed observable injury Described as burning, tingling, shooting, stabbing, electrical 15 Nociceptive = Neuropathic Nociceptive Pain – Activation of pain receptors – Associated with acute or ongoing tissue injury – Sharp, aching, throbbing, dull Neuropathic – Nerve injury – Aberrant processing in CNS or PNS – Burning, pins and needles, shock-like, electrical, numb, stabbing Patients report equal severity for both types of painRequire different medications 16 WHO 3-step Pain Ladder moderate (5-6) severe (7-10) Morphine Hydromorphone Methadone A/Codeine Levorphanol A/Hydrocodone Fentanyl A/Oxycodone Oxycodone ASA A/Dihydrocodeine ± Adjuvants Acetaminophen Tramadol NSAIDs ± Adjuvants mild (1-4) ± Adjuvants 17 Principles of Analgesic Use for the WHO Ladder By the mouth-use the simplest route By the clock-give scheduled doses By the ladder- select level by pain intensity Individualize treatment Monitor response Use adjuvant drugs as needed Prevent and treat side-effects 18 Efficacy of WHO Analgesic Ladder to Treat Pain in ESRD Ahmad S. Barakzoy, MD Alvin H. Moss, MD Section of Nephrology WVU School of Medicine 19 172 Eligible Hemodialysis Patients 29 excluded because they lacked decision-making capacity, had a prior history of drug abuse, or were hospitalized during the study. 143 Patients (83%) Participated in the Study 65 Reported No Pain 78 (54%) Reported Pain 16 Already Being Treated for Pain 17 Refused to Take Pain Medications 45 (58%) Completed the pre-andpost-treatment evaluation Demographics n = 45 Mean Age Gender Race Diabetics 65 ± 12.5 years 53% Male 47% Female 38 Caucasian (84%) 7 African American (16%) 49% Mean Initial Pain Score by Demographic 10 9 8.0 7.9 7.6 7.5 8 7.8 7.4 7 6 5 4 3 2 1 Men Women P=0.13 Under 65 65 and Over P=0.544 White P=0.406 Black Comparison of Initial and Post Treatment Mean Pain Scores n = 45 10 7.8 9 8 7 6 5 4 1.6 3 2 1 Initial P < 0.001 Post Treatment Type of Pain Reported by Patients 50% 40% 45% 40% 31% 29% 35% 30% 25% 20% 15% 10% 5% 0% Neuropathic Nociceptive Type of Pain Both Qualitative Description of Pain 60% 55% Percent of Patients 50% 40% 27% 30% 21% 20% 10% 9% 10% 4% 4% Cramping Gnawing 0% Burning Aching Sharp Stabbing Throbbing Comparison of Initial and Post-Treatment Pain Scores 10 9 8.1 7.4 8 7 6 Initial Pain Score P=0.110 Post Treatment Pain Score 5 P=0.524 4 3 1.5 1.8 2 1 0 Neuropathic Pain Nociceptive Pain Type of Pain Oxycodone and Hydrocodone Initial and Post Treatment Comparison 8.9 10 9 7.4 8 Initial Pain Score P=0.001 7 Post Pain Score P=0.801 6 5 4 3 1.4 1.5 2 1 Oxycodone Hydrocodone Comparison of Initial and Post Treatment Pain Scores by Age 10 9 7.9 7.6 8 7 6 5 Initial Pain Score P=0.544 Post Treatment Pain Score 4 P=0.003 2.1 3 0.94 2 1 0 Under 65 65 and Over Reduction of Total McGill Pain Questionaire Score 17.3 18 16 14 12 10 8 4.3 6 4 2 0 Initial P<0.001 Post Treatment Percentage of Patients Who Were Prescribed Drug *Percentages do not add up to 100% due to 24% of patients receiving a combination of drugs 40 38% 35 27% 30 24% Percent 25 20% 16% 20 15 10 2% 5 0 gabapentin hydrocodone tramadol oxycodone nortriptyline propoxyphene Studies included in review CC=cancer center; PCU=palliative care unit; IMH=internal medicine hospital; GH=general hospital; PRU=pain relief unit Jadad et al. The WHO Analgesic Ladder for Cancer Pain Management. 31 JAMA 1995;274:1870-1873 Efficacy of WHO 3-Step Analgesic Ladder Approach 100% 2005 WV Palliative Care Network N=218 100% WVU Dialysis Patients N=45 96% 85% 60% 40% 20% 80% % Adequate Analgesia % Adequate Analgesia 80% 60% 40% 20% 27% 0% 0% 0% T0 T48 Hours T0 T4 Weeks 32 QOL Outcomes from Pain Management Improved function – “I am able to walk to my mailbox, something I could not do before because of hip and leg pain.” Better ability to tolerate dialysis – “I am able to tolerate 4 hours of dialysis without the severe back pain.” More restful sleep – “I have more energy because I am resting better at night.” 33 Pain Medications in ESRD Safe and Effective Use with Caution Fentanyl Methadone Hydromorphone Oxycodone Do Not Use Codeine Meperidine Morphine Propoxyphene Expanded from Dean M: Opioids in Renal Failure and Dialysis Patients. 34 J Pain Symptom Manage 28:497-504. 2004. Opioid Dose Adjustment Dose escalation until development of adequate analgesia or unacceptable side effects. Rate of escalation depends on severity of pain. Increase daily dose by 25 -50 % for mild to moderate pain, 50-100% for severe pain. Increase rescue dose as baseline dose is increased-10% of total daily dose Add adjuvant medications to improve analgesia Prevent and treat side-effects 35 Indications for Opioid Rotation Intolerance to side-effects of drug Pain not satisfactorily controlled Loss of oral route (emesis,dsyphagia) Cost issues Convenience/compliance issues Drug abuse concerns 36 Incomplete Cross-Tolerance Subtle differences in the molecular structure of each opioid and the way they interact with receptors Helps explain variance between patient’s effective ratio and equianalgesic ratio calculations Approach to deal with this phenomenon: 1) if pain well controlled --> start with 5075% of calculated dose, and titrate up 2) if pain poorly controlled, use 90-100% calculated dose 37 Transdermal Fentanyl Good choice for patients with stable level of pain Good choice for dysphagic patients Do not use in the opioid-naïve 38 Transdermal Fentanyl Steady state between patch, subdermal pool, and circulation Patch size: mcg/hr: 25,50,75,100 $$$ Change q 3 days ( 20% q 2 days) Fever, heat increase drug effect Assure good contact with skin Cover with ATC opioids for first 15-20 hours Requires short-acting opioid for rescue 39 Barriers to Effective Pain Management in ESRD Lack of recognition of the problem Complicated pharmacokinetics Until our study treatment algorithms for cancer patients had not been validated for ESRD patients Uremic symptoms may mimic opioid toxicity 40 Safe Pain Management 41 Distinguish Opioid State Opioid-naïve patients – “Start low, go slow” – e.g., hydromorphone 0.2 mg IV bolus or 1 mg po Opioid-tolerant – Use equianalgesic table – Adjust for incomplete cross-tolerance – CNS depression precedes respiratory 42 Equianalgesic Doses of Opioid Analgesics Oral/rectal Dose (mg) Drug Parenteral dose (mg) 30 Morphine 10 10-15 Oxycodone - 150 Meperidine 50 7.5 Hydromorphone 1.5 2 Levorphanol 15 Hydrocodone 1 43 Incomplete Cross-Tolerance Subtle differences in the molecular structure of each opioid and the way they interact with receptors Helps explain variance between patient’s effective ratio and equianalgesic ratio calculations Approach to deal with this phenomenon: 1) if pain well controlled --> start with 5060% of calculated dose, and titrate up 2) if pain poorly controlled, use 90-100% calculated dose 44 Opioid adverse effects Common Uncommon Constipation Bad dreams / hallucinations Dry mouth Dysphoria / delirium Nausea / vomiting Myoclonus / seizures Sedation Pruritus / urticaria Sweats Respiratory depression Urinary retention When should methadone be considered? Inadequate analgesia from other opioids – neuropathic component to pain Opioid intolerance due to other sideeffects Neurotoxicity with other opioids Cost is a primary factor 46 A Role for Palliative Care The patient is an 87 yr old man with ESRD from hypertension who was admitted from a NH with altered mental status. The patient has been on dialysis for 4 years and is transported by ambulance for his treatments. Other medical problems include inoperable coronary artery disease, CVA with L hemiplegia, dementia, UGI bleeding, COPD, and PVD with gangrene of three toes on his right foot. 47 A Role for Palliative Care The patient is unable to walk or transfer himself from chair to stretcher. He complains of severe pain in his right foot. He usually screams during dialysis and seems uncomfortable. The wife does not like him to receive pain medication because he becomes less responsive. What should be done? 48 What did we do? Start low, go slow with oxycodone Added acetaminophen as adjuvant RTC Educated wife about pain management 49 What’s the problem? A 57 year-old dialysis patient is admitted with severe pain all over her body, especially in her joints. She has nephrogenic fibrosing dermopathy. Her current pain medicine is extended-release morphine 200mg po q8h. Despite this dose, she is still in pain. She also complains of increasingly severe jerking. It is so bad that her body jumps six inches off her chair at times. What’s going on and what should you do? 50 What did we do? Diagnosed opioid neurotoxicity – Morphine metabolites accumulate in CKD Need to distinguish from uremic encephalopathy from underdialysis – Myoclonus in both – Asterixis in both – Somnolence in both – Hallucinations in both 51 Opioid Neurotoxicity Myoclonus-uncontrollable twitching and jerking of muscles or muscle groups, usually occurs in the extremities. Hyperalgesia-increased sensitivity to noxious stimuli or even light touch Delirium with hallucinations Grand mal seizures-late 52 How to Treat Opioid Neurotoxicity Stop opioid or reduce dose if pain allows Start new opioid Treat jerking with benzodiazepines – clonazepam 0.5mg BID or TID po – lorazepam 1-2 mg po q8h 53 Conclusions Use of the WHO 3-step analgesic ladder results in adequate pain relief in most ESRD patients. Opioids have significant adverse effects which can be anticipated and treated. 54 Kidney End-of-Life Coalition www.kidneyeol.org American Association of Kidney Patients American Kidney Fund American Nephrology Nurses’ Association Center for Medicare & Medicaid Services DaVita Dialysis Clinics, Inc. Forum of ESRD Networks Fresenius Medical Care National Hospice and Palliative Care Organization National Kidney Foundation National Renal Administrators Association Renal Advantage, Inc. Renal Physicians Association West Virginia University 55 Take-Home Messages Assess pain systematically Choose drugs that are safe in CKD Start pain meds according to severity and nature of pain and titrate Anticipate adverse effects and warn patient Start stimulant laxative at same time as opioid 56