ESRD

Question 1

Epidemiology of ESRD

Answer 1

• Increasing acceptance of dialysis, particularly in the elderly population
• Increased survival on dialysis

Question 2

Prognosis on dialysis

Answer 2

• Life expectancy is poor
• Overall 1 year survival 23%, 5 year survival 60%
• Mortality of patients over the age of 75 with comorbidities approaches 50% within 6 months!
• Increased age, low serum albumin, poor functional status, and comorbidities are poor prognostic factors

Question 3

Conservative management for ESRD

Answer 3

• Active disease management (anemia, metabolic bone disease, electrolyte abnormalities) and aggressive palliative care
• Appropriate for any patient who decides risks/burdens of dialysis outweigh benefits
• May remain stable for long periods of time rather than imminent death (contrast with high rates of decline or death before and after initiating dialysis)
• Some patients may have improved quality of life and a survival advantage as compared to on dialysis

Question 4

Pain and ESRD

Answer 4

• Common in ESRD patients (50%) whether on chronic dialysis or being treated conservatively
• Typically multifactorial and progressive
• MSK pain is most common (renal bone disease, osteoarthritis, etc.)

Question 5

Causes of pain in ESRD

Answer 5

1. Primary renal disease
   - PCKD
   - MM
2. ESRD related
   - Renal bone disease (soft tissue/periarticular calcification)
   - Dialysis-related amyloidosis (soft tissue/periarticular calcification - dialysis does not filter out amyloid)
   - Peripheral neuropathy
   - Calciphylaxis (disruption in phos/Ca+ metabolism, resulting in tissue ischemia and necrosis from calcific uremic arteriolopathy)
   - Nephrogenic systemic fibrosis
3. Dialysis complications
   - Ischemic neuropathy from AV fistulas
   - Osteomyelitis or discitis (central lines)
   - Abdominal wall distention, lower back strain from peritoneal dialysis
   - Recurrent cramps, HA, symptomatic hypotension, abdo pain, N/V during dialysis
4. Comorbidities
   - Diabetic neuropathy
   - PAD
   - OA

Question 6

Analgesics in ESRD

Answer 6

Non-opioids

• Acetaminophen generally considered safe
• NSAIDs and ASA may potentiate platelet dysfuction of uremia (increased risk of bleeding) and can accerlate loss of renal function
• Low dose ASA for cardiac protection usually tolerated, avoid NSAIDs otherwise

Opioids

• Active opioid metabolites excreted via kidneys, can accumulate in patients with ESRD and lead to opioid toxicity (esp M3G)
• Avoid morphine, meperidine, codeine)
• Oxycodone can be used with caution (active metabolite - oxymorphone - of uncertain significance in ESRD), use IR only
• Tramadol will accumulate, but may be used with caution
• Hydromorphone, fentanyl, methadone, buprenorphine considered safe
• H6G is renally excreted, but better tolerated than morphine and can be used for dialysis patients with monitoring

Question 7

Safe analgesics in renal failure

Answer 7

1. Hydromorphone
   - H6G renally excreted, but better tolerated than morphine (can use with monitoring)
   - Once dosing is stablised, convert to fentanyl patch and limited HM to lower PRN doses
2. Fentanyl
   - Rapidly metabolisted in the liver
   - No clinically significant accumulation in ESRD
3. Methadone
   - Excreted in feces and does not appear to accumulate in ESRD
4. Buprenorphine
   - Pharmcokinetics minimally altered in ESRD
   - May be effective for chronic pain in ESRD, but limited evidence to support
5. Acetaminophen
   - Max daily dose 3.2g/day (2.6g/day in those with chronic stable liver disease or if malnourished)

Question 8

Medications for neuropathic pain in ESRD

Answer 8

1. Gabapentin (first line in ESRD)
   - 100mg Po qHS, given after dialysis on HD days
   - Increase by 100mg q weekly to a max dose of 600mg/HS
   - Monitor for CNS effects at doses over 300mg/day (nystagmus, ataxia, tremor, somnolence, reduced LOC)
2. TCAs (second line, switch to TCA if gabapentin ineffective)
   - Note metabolites excreted via kidneys and not effectively removed by dialysis
   - No need to dose reduce, but less predictibility in response to doses, and side effects may exacerbate issues already present (dry mouth, orthostasis, somnolence, urinary retention)
   - Start desipramine 10mg PO qHS (max dose 50) or nortriptyline 10mg PO qHS
   - If ineffective after 4-6 weeks, consider methadone.

Question 9

CNS side effects of gabapentin

Answer 9

• Nystagmus
• Ataxia
• Tremor
• Somnolence
• Reduced LOC

*Particularly with doses > 300mg/day

Question 10

Depression in dialysis patients

Answer 10

• Common in dialysis patients, prevalence 5-50%
• SSRIs are first line, despite lack of evidence in ESRD
• Hepatically metabolised and metabolites are excreted by the kidneys
• Fluoxetine, norfluoxetine, sertraline, and citalopram appear to be minimally changed in patients with ESRD
• Most evidence for fluoxetine
• Start at 50% usual starting dose and titrate slowly
• Only use TCAs for treatment resistant depression or for those with additional indication (e.g. neuropathyic pain), and SNRIs/NDRIs should be avoided (renally excreted, lack of evidence)

Question 11

Lithium in ESRD

Answer 11

• Single dose (usually 600mg) after each dialysis session
• Lithium levels before and after dialysis sessions required to establish therapeutic dose as lithium is readily dialysed

Question 12

Frailty in dialysis patients

Answer 12

• Dialysis patients have some of the highest prevalence rates for frailty
• 79% of dialysis patients over 80 years
• Associated with increased morbidity, hospitalization, early mortality
• Dialysis may not be as beneficial and patients may fare better with conservative management
• For most patients age 65 and over, dialysis does not result in a return to pre-dialysis level of functioning

Question 13

Cognitive deficits in CKD

Answer 13

• Cognitive deficits tend to appear early in CKD, before transition to ESRD
• By the time patients start dialysis, 73% have either mod or severe cognitive impairment on formal neurocog testing
• Dementia tends to predict mortality
• Dementia can impact EOL decision making and advance care planning
• Consider using the MOCA to screen

Question 14

Importance of facilitated advance care planning in patients with ESRD

Answer 14

1. Burden of disease
   - High mortality rates
   - High prevalence of suffering, frailty, cognitive dysfunction
   - Patients need to know prognosis and establish GOC early to ensure timely decision making re: initiation/withdrawal of dialysis
2. Consideration of circumstances under which dialysis should be stopped
3. Cognitive impairment
   - Process should start early and may require ongoing communication and re-evaluation
   - Majority of patients would not want to continue dialysis with significant cognitive impairment

Question 15

When is it appropriate to stop dialysis?

Answer 15

1. Patients with decision-making capacity, who request dialysis discontinuation. Voluntary decision with full informed consent
2. Patients who no longer possess decision-making capacity, but previously indicated refusal of dialysis in an oral or written advance directive
3. Patients who no longer possess decision-making capacity and whose SDM refuse dialysis or request that it be discontinued, based on the previous wishes or best interest of the patient
4. Patients with profound, irreversible neuro impairment, such that they lack signs of thought, sensation, purposeful behaviour, and awareness of self and environment
5. Patients with a medical condition that precludes the technical process of dialysis (note that this does not include age, comorbidity, and functional status per se)

Question 16

Average survival and QOL after stopping chronic dialysis

Answer 16

8 - 10 days (though reports of 1-48 days)

• Symptom burden is often high in the last days of life (pruritis, nausea, dyspnea, agitation, myoclonus) due to toxin accumulation

Question 17

Common symptoms in dialysis patients

Answer 17

• Anxiety/depression
• Pain
• Pruritis
• Restless legs
• Sleep disturbance
• Fatigue
• N/V
• Dyspnea
• Drowsiness
• Decreased appetite

Question 18

Management of fatigue in dialysis patients

Answer 18

• Often multifactorial (anemia, hyperparathyroidism, uremia, dietary and fluid restrictions, malnutrition, side effects of meds)
• Consider and exclude other causes (hypoprathyroidism)
• Consider use of EPO

Question 19

Management of N/V in ESRD

Answer 19

1. Due to delayed gastric emptying/gastroparesis
   - Metoclopramide (dose reduce by 50%, not increased risk of EPS)
2. Uremia or drug related nausea
   - Haldol (dose reduce)
   - Ondansetron (watch for constipation as a side effect, may also help with uremic pruritus)
3. Gastritis
   - Consider a PPI (common in uremic patients)

Question 20

Management of ESRD pruritis

Answer 20

Basics:

• Regular mosturizing with nonfragrant topical emolliants, especially after bathing
• Non-irritating, loose clothing
• Avoidance of skin irritants (perfumes)
• Cool, humidified environment

2. Gabapentin
   - Start at low doses (100mg after each dialysis session)
   - Avoid in patients who have stopped dialysis due to risk of toxicity
3. Oral antihistamines (if not on dialysis)
   - Hydroxyzine
4. Sertraline (if not on dialysis)
   * Note ondansetron may also be effective for uremic pruritus

Question 21

Management of restless leg syndrome in ESRD

Answer 21

• Correct iron deficiency, low PTH, hyperphos
• Avoid exacerbating agents (caffeine, sedative antihistamines, maxeran, TCAs, SSRIs, lithium, dopamine agonists)
• Consider gabapentin (if not on dialysis) or clonazepam

Question 22

Management of sleep disturbance in ESRD

Answer 22

• Sleep hygiene
• Rule out sleep apnea
• Consider hypnotics (temazepam 7.5mg) but note that ESRD patients may be sensitive to benzos

Question 23

Confusion and agitation in ESRD

Answer 23

• Combine neuroleptic (haldol) and benzo (midaz)