Management of pain in patients with renal insufficiency or end-stage renal disease on dialysis

byAbdelwahab Ward, BS Pharm, PharmD - last updated
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OVERVIEW ã…¡ Pain is a common problem in patients with renal insufficiency and end-stage renal disease (ESRD) and can have a significant effect on the patient’s quality of life. When assessing a patient’s pain, assess both the severity of the pain (such as on an analogue scale, 0-10) and the characteristics of the pain (see Figure 1). Pain is most commonly characterized as nociceptive, neuropathic, or both. Nociceptive pain can be further classified as arising from either somatic or visceral sources and described as dull, throbbing, cramping, and/or pressure like. Neuropathic pain is often described as tingling, numbing, burning, and/or stabbing.

NSAIDs are associated with dose-dependent acute renal failure, gastrointestinal ulceration and bleeding, and cardiac events. The nonopioids that are considered safe options in patients with renal insufficiency include acetaminophen, ibuprofen, and fenoprofen. However, in the elderly, American Geriatric Society (AGS) guidelines currently recommend avoiding all NSAIDs due to their safety profile in the geriatric population. (See Table 1, Pain medications in CKD/ESRD).

Acetaminophen is considered one of the safest agents to use for the treatment of pain, in renal patients. Ibuprofen is metabolized in the liver to inactive compounds. It does not accumulate in renal insufficiency, and two of the inactive compounds are dialyzable. It is considered a safe option for the treatment of pain in patients with renal insufficiency or dialysis. Fenoprofen is metabolized in the liver to inactive compounds. Renal impairment is likely to cause the accumulation of the inactive metabolites but not the parent compound, so dose reduction is not necessary with the use of this agent in renal insufficiency or dialysis. Naproxen is metabolized in the liver to inactive compounds. Use of naproxen is not recommended in patients with moderate to severe renal impairment. If therapy must be initiated, close monitoring of the patient’s renal function is recommended. COX-2 inhibitors (Celebrex) should be avoided in severe renal impairment and in those on dialysis.

Opioids in renal disease. Fentanyl, hydrocodone, and hydromorphone are the safest opioids to use in renally impaired and dialysis patients. Tramadol in lower doses may also be safely used in renally impaired and dialysis patients. Low-dose gabapentin and lidocaine patches can be safely used as adjunctive therapy in renally impaired and dialysis patients; TCAs may also be used in lower doses in renally impaired patients. (See Figure 2, World Health Organization (WHO) analgesic ladder adapted for patients with advanced chronic kidney disease).

Table (1). Pain Medications in CKD/ESRD
Recommended Use with Caution Do Not Use
Acetaminophen
 Tramadol

Limit dose to 50 mg BID. Higher doses have been used but caution needs to be taken since pharmacokinetics are not well established.		 Morphine
Hydromorphone

Hydromorphone is potentially unsafe if the patient stops dialysis OR is CKD stage 4 or 5. The kidney-excreted active metabolite, hydromorphone-3-glucuronide, build ups because it is not adequately cleared in worsening CKD.		 Hydrocodone/Oxycodone

Insufficient pharmacokinetic evidence to establish safety in CKD, but literature reports use without major adverse effects.		 Codeine
Fentanyl
 Desipramine/Nortriptyline

Alternative to treat neuropathic pain, but more adverse effects than gabapentin and pregabalin.		 Meperidine
Methadone Propoxyphene
Gabapentin

Doses in ESRD up to 300mg/day are generally considered safe, but higher doses should be used with caution; note that gabapentin use for neuropathic pain is off-label but effectiveness has been documented.		 Renally excreted metabolites accumulate in CKD causing neurotoxicity.
Pregabalin

Doses up to 100 mg/day are generally considered safe in ESRD.

MANAGE PAIN IN RENAL PATIENTS

Hydromorphone. Start at 0.5 mg PO q 2 hours PRN pain and titrate dosage every 2–3 days. If pain is not controlled, continuous and 24‐hour dose exceeds 12 mg, substitute transdermal fentanyl 25 mcg/hr for regular dose of hydromorphone. If further “as needed” hydromorphone exceeds 12 mg/24 hours, increase dose of fentanyl patch by further 25 mcg. Titrate upwards in similar manner if pain is not controlled.
  • CAUTION: Toxic metabolite, H3G, can potentially accumulate if dialysis is stopped OR if patient is CKD stage 4 or 5.

Fentanyl transdermal patches. Useful for patients with chronic and stable pain. Start after immediate‐release opioid dose is established. Analgesia may not be obtained for 12‐24 hours, so continue previous PRN analgesics for 12 hours to ensure a smooth transition. Initial dose for opioid‐naïve patients is 12 mcg/hr (increase dose every 3–6 days as needed for pain). Useful choice if dialysis non‐adherence or stopping dialysis are concerns. Fentanyl patches above 12 mcg/hr should not be used in opioid‐naïve patients due to risk of respiratory depression. Since fentanyl patches are long acting, breakthrough pain medications should also be prescribed.

Methadone. Only recommended to be used by knowledgeable physicians in consultation with a pain management specialist. Use if unable to control pain with fentanyl or hydromorphone (opioid‐allergy, adverse effects, or refractory pain). Obtain baseline QTc (methadone may prolong QT interval) and repeat EKG if daily dose > 100 mg. QTc < 500 ms considered safe. Beware of multiple drug interactions and adjust dose.

TREATMENT BASED ON PAIN TYPE

Nociceptive Pain Treatment. Confirm patient is able to swallow oral medications. Establish a pain control regimen utilizing short acting opioids and monitor for opioid toxicity and adverse effects. A rescue dose equivalent to 10% of the 24‐hour dose of opioid should be available to be taken every 1‐2 hours PRN for breakthrough pain. Remember to recalculate the rescue dose when increasing the base dose (long‐acting dose). Long‐acting opioids should be started after the needed dosage to control pain is established with short‐acting opioids. If the patient is experiencing pain when he/she takes the long‐acting opioid, he/she should take a rescue dose at the same time and not expect the long‐acting opioid to relieve the breakthrough pain.
  • NOTE: Monitor for opioid toxicity (sedation, hallucinations, myoclonus, and/or asterixis) and opioid adverse effects (constipation, nausea, and vomiting).

Neuropathic Pain Treatment. Use Gabapentin (Gaptin) 100 mg PO qhs and increase weekly by 100 mg per night to a maximum of 300 mg qhs. Occasionally doses up to 600 mg a day can be safely used. If ineffective at maximum tolerated dose, discontinue and start pregabalin (Lyrica) 25 mg qhs and increase every few days to 100 mg a day. If pain control is inadequate at target dose for 2 to 4 weeks, or intolerable adverse effects, discontinue and start desipramine 10 mg PO qhs. Titrate to adequate pain control or maximum dose of 150 mg qhs. If pain control still remains inadequate, institute WHO 3‐Step Analgesic Ladder (see Figure 2).

REFERENCES

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