Palliative Care Issues in

End Stage Renal Disease

Mike Harlos MD, CCFP, FCFPMedical Director, WRHA Palliative CareMedical Director, St. Boniface Hospital Palliative Care

http://palliative.info

http://virtualhospice.ca

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.

SUFFERINGEMOTIONALPSYCHOSOCIAL

PHYSICAL

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

Cure/Life-prolongingCure/Life-prolongingIntentIntent

Palliative/Palliative/Comfort IntentComfort Intent

Bereavement

Bereavement

DEATH

“Active Treatment”

PalliativePalliativeCareCare

DEATH

EVOLVING MODEL OF PALLIATIVE CARE

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

TYPES OF PAIN

NEUROPATHICNOCICEPTIVE

Somatic Visceral

Deafferentation Sympathetic Maintained

Peripheral

COMPONENT DESCRIPTORS EXAMPLESSteady,

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

FEATURES OF NEUROPATHIC PAIN

Morphine and HydromorphoneActive 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

• Phenothiazine neuroleptic• Dopamine antagonist, with histamine and muscarinic

receptor antagonism as well (effective general antinauseant)

• Oral, sublingual, subcutaneous routes

Nozinan (methotrimeprazine)

• benzodiazepine• Subcutaneous route; about 1/3 as potent as IV route• Can mix with methotrimeprazine in same syringe

Versed (midazolam)

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

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.

0

10

20

30

40

50

60

< 3 3 - 10 > 10

Survival Time Following Discontinuation of Dialysis (Days)

# P

atie

nts

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

Communication Anticipating need for non-oral medication routes Communication

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)