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

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World Health Organization Definition 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.

PHYSICAL SUFFERING PSYCHOSOCIAL EMOTIONAL SPIRITUAL

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

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

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

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

FEATURES OF NEUROPATHIC PAIN COMPONENT DESCRIPTORS EXAMPLES Steady, Dysesthetic Burning, Tingling Constant, Aching Squeezing, Itching Allodynia Hypersthesia Diabetic neuropathy Post-herpetic neuropathy Paroxysmal, Neuralgic Stabbing Shock- like, electric Shooting Lancinating trigeminal neuralgia may be a component of any neuropathic pain

Morphine and Hydromorphone Active Metabolite Accumulation in Renal Failure

Vicious Cycle of Opioid-Induced Neurotoxicity

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

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”

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

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

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

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

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

Communication Issues in Sedation for Delirium at End of Life (e. g 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

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

Dyspnea Management Pharmacological 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

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

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

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

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

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 Anticipating need for non-oral medication routes

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)