Palliative Care Issues in End Stage Renal Disease

1. Palliative Care Issues in End Stage Renal Disease Mike Harlos MD, CCFP, FCFP Medical Director, WRHA Palliative Care Medical Director, St. Boniface Hospital Palliative Care

4. http://palliative.info

5. http://virtualhospice.ca

6. PALLIATIVE CARE: World Health Organization Definition Palliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual.

7. PHYSICAL SUFFERING PSYCHOSOCIAL EMOTIONAL SPIRITUAL

8. Specific Issues • Where does RRT fit in Palliative Care? • Where does Palliative Care fit in RRT? • What are some of the unique symptom control challenges in ESRD • Communication issues

9. D E A T H D E A T H EVOLVING MODEL OF PALLIATIVE CARE “Active Treatment” Palliative Care Cure/Life-prolonging Intent Palliative/ Comfort Intent Bereavement

11. Pain Control • Variety of pain etiologies in ESRD • Neuropathic (diabetic neuropathy) • Ischemic (causes nociceptive, visceral, and neuropathic pains) • Renal insufficiency has significant implications for opioid choice – morphine and hydromorphone have active metabolites which accumulate

12. TYPES OF PAIN NOCICEPTIVE NEUROPATHIC Somatic Visceral Deafferentation Sympathetic Maintained Peripheral

13. FEATURES OF NEUROPATHIC PAIN

14. Morphine and HydromorphoneActive Metabolite Accumulation in Renal Failure

15. Vicious Cycle of Opioid-Induced Neurotoxicity

16. Codeine • Metabolized to C-6-G, norcodeine, and morphine • Guay et al 1987 – found accumulation of codeine in hemodialysis patients (t1/2 19 hrs) relative to healthy volunteers (t1/2 4 hrs) • Dose reduction suggested in renal failure: • Clcr 10-50 ml/min: Administer 75% of dose • Clcr <10 ml/min: Administer 50% of dose • Morphine metabolites will also accumulate

17. Methadone • NMDA receptor antagonist – unique role in neuropathic pain, preventing tolerance and neurotoxicity • Becoming a preferred opioid in renal insufficiency • Inactive metabolites • Approx. 20% excreted unchanged in urine, the remainder of the parent drug and metabolites excreted through feces • As renal function deteriorates, there is increased elimination through feces without increased plasma concentrations • Nonetheless, “start low and go slow”

18. Fentanyl • Inactive metabolites • No dosage modification needed when administered as a bolus, but accumulation occurs with chronic dosing • Koehntop DE, Rodman JH. Fentanyl pharmacokinetics in patients undergoing renal transplantation. Pharmacotherapy 1997 • Marked decreases in fentanyl clearance, related to degree of azotemia • Chronic dosing empirically titrated to effect

19. Oxycodone • Kirvela et al, The Pharmacokinetics of Oxycodone in Uremic Patients Undergoing Renal Transplantation, J Clin Anesth 1996 • Mean elimination half-life was prolonged in uremic patients due to increased volume of distribution and reduced clearance. • Conclusions: Elimination of oxycodone is impaired in end-stage renal failure • “start low and go slow” approach, with empirical titration to effect

20. Meperidine (Demerol®) • Neurotoxic metabolite normeperidine, which accumulates in renal insuff. • May cause seizures, death • Should not be used in chronic dosing, regardless of renal function

21. Delirium at End of Life • Common: 80 – 90% in last few weeks • Almost always multifactorial; illness, medications • May rapidly worsen, with paranoia and agitation • Very distressing for all involved • Not likely to be reversible in last few days of life, such as after D/C dialysis • Main intervention is effective sedation

22. Common Medications for Sedation in Terminal Delirium Nozinan (methotrimeprazine) • Phenothiazine neuroleptic • Dopamine antagonist, with histamine and muscarinic receptor antagonism as well (effective general antinauseant) • Oral, sublingual, subcutaneous routes Versed (midazolam) • benzodiazepine • Subcutaneous route; about 1/3 as potent as IV route • Can mix with methotrimeprazine in same syringe

23. Communication Issues in Sedation for Delirium at End of Life (e.g. Dialysis Withdrawal) • Delirium not reversible; ongoing physiologic decline • Once effectively sedated, will not likely awaken again • Medications not hastening process, but ensuring comfort • Encourage ongoing communication by family, including private time alone with patient • Be cautious in presenting “non-choices” as choices… there no other realistic options but aggressive sedation in trying to settle a restless, agitated, delirious person who is imminently dying

24. Dyspnea • In prospective studies approaches 80% in final days • Effectively controlled in < 50% in studies • Multifactorial • Pneumonia is a common final event • Treatment requires urgency: • often rapid progression • severe distress • often only hours before dying

25. Dyspnea Management • Non-Pharmacological • Calm reassurance • Fan • Open window • Sitting upright • Pharmacological • Oxygen • Opioids – may need aggressive titration with IV boluses q10 min with escalating dose • Sedatives – Neuroleptics (methotrimeprazine) or Benzodiazepines • Antisecretory agents – scopolamine, glycopyrrolate

26. Pruritus • Common in ESRD; prevalence 50 – 90 % • Various etiologies suggested - e.g.: • inadequate dialysis • secondary hyperparathyroidism • dry skin • divalent ion accumulation and precipitation in skin • mast cell dysregulation • abnormal cutaneous innervation • aluminum toxicity • elevated serum histamine • elevated serum serotonin • substance P • altered immune function • others

27. Potential Treatments For Uremic Pruritus • optimizing dialysate concentrations of magnesium and other divalent ions • emollients and moisturizers • ultraviolet B light • Naltrexone (opioid antagonist) – conflicting results in randomized crossover trials; don’t use if needs opioids • Thalidomide – effective in > 50% of patients; Note: fetal malformations… use appropriate caution in women • Capsaicin cream may help in localized itch • Mirtazapine – antidepressant – H1 , 5HT2 , and 5HT3 receptor blocker

29. Potential Treatments For Uremic Pruritus ctd • H1 antihistamines ineffective • Ondansetron – recently found to be no more effective than placebo in randomized double-blind trial

30. Withdrawal of Dialysis Catalano C et al, Withdrawal of renal replacement therapy in Newcastle upon Tyne: 1964-1993. Nephrol Dial Transplant. 1996 Jan;11(1):133-9. n = 88 Median survival = 8 days

31. Withdrawal of Dialysis – Palliative Issues in Ensuring Comfort • Communication • Anticipating symptoms, aggressive response • Pain (generally only if a pre-existing problem) • Nausea • Restlessness, confusion • Dyspnea – fluid balance, pneumonia • Pruritus • Myoclonus, twitching • Communication • Anticipating need for non-oral medication routes • Communication

32. Common Communication Issues • Treatment decisions - “Would you prefer the rock, or the hard place?” • Food and fluids • Withdrawing or withholding treatment seen as euthanasia • Sedation is seen as euthanasia • “You wouldn’t let an animal die this way” • Everyone would be better off if I’d just die • How long have I got? • How will I die? (rarely asked, always worried about)