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

6. 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.

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. EVOLVING MODEL OF PALLIATIVE CAREH
“Active
Treatment”
Palliative
Care
Cure/Life-prolonging
Intent D E A T H
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. Sympathetic Maintained
TYPES OF PAIN
NOCICEPTIVE
NEUROPATHIC
Somatic
Visceral
Deafferentation
Sympathetic Maintained
Peripheral

13. 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

14. Morphine and Hydromorphone Active 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 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
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 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

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:
Nephrol Dial Transplant 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
Anticipating need for non-oral medication routes

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)