Palliative Care Issues in End Stage Renal Disease

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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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http//palliative.info
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http//virtualhospice.ca
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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.
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PHYSICAL
SUFFERING
PSYCHOSOCIAL
EMOTIONAL
SPIRITUAL
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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

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EVOLVING MODEL OF PALLIATIVE CARE
Active Treatment
Palliative Care
Cure/Life-prolonging Intent
Palliative/ Comfort Intent
Bereavement
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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

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TYPES OF PAIN
NOCICEPTIVE
NEUROPATHIC
Somatic
Visceral
Deafferentation
Sympathetic Maintained
Peripheral
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FEATURES OF NEUROPATHIC PAIN
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Morphine and HydromorphoneActive Metabolite
Accumulation in Renal Failure
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Vicious Cycle of Opioid-Induced Neurotoxicity
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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 lt10 ml/min Administer 50 of dose
• Morphine metabolites will also accumulate

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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

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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

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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

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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

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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

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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

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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

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Dyspnea

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

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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

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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

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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 dont use
  if needs opioids
• Thalidomide effective in gt 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

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Potential Treatments For Uremic Pruritus ctd

• H1 antihistamines ineffective
• Ondansetron recently found to be no more
  effective than placebo in randomized double-blind
  trial

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Withdrawal of Dialysis
Catalano C et al, Withdrawal of renal
replacement therapy in Newcastle upon Tyne
1964-1993. Nephrol Dial Transplant. 1996
Jan11(1)133-9.
n 88 Median survival 8 days
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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

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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 wouldnt let an animal die this way
• Everyone would be better off if Id just die
• How long have I got?
• How will I die? (rarely asked, always worried
  about)