Analgesia in Kidney Disease

Analgesia in kidney disease depends on avoiding nephrotoxic drugs and drugs with active renal metabolites. Paracetamol is the base, and opioids are chosen by their metabolism, with lower doses and longer intervals.

Opioid metabolism. Morphine, codeine and pethidine have active metabolites (morphine-6-glucuronide, norpethidine) that accumulate and cause sedation, respiratory depression and seizures. Fentanyl, buprenorphine and alfentanil are metabolised mainly in the liver.

NSAIDs. They reduce renal blood flow and cause acute injury, hyperkalaemia and fluid retention.

Step one. Paracetamol 1 g orally or intravenously every 6 hours (8 hours if clearance is under 10 mL/min), maximum 4 g daily, and 15 mg/kg with a maximum of 60 mg/kg daily if under 50 kg.

NSAIDs. Avoid when eGFR is under 30, in acute kidney injury, and with a renin-angiotensin blocker plus diuretic. Short courses may be used at eGFR 30 to 59 with hydration. Topical NSAIDs have little absorption and are acceptable for localised pain.

Opioids. Preferred: fentanyl, buprenorphine, or low-dose oxycodone or hydromorphone. Avoid: morphine, codeine, dihydrocodeine and pethidine.

Neuropathic pain. Gabapentin or pregabalin at renal doses, or amitriptyline 10 mg at night.

Special groups.

• Children: dose by weight, extending intervals.

• Pregnancy: paracetamol first line; avoid NSAIDs after 20 weeks and earlier where possible.

• Older adults: start at the lowest dose and monitor for sedation.

• East Africa: where oral morphine is the only opioid available, give 1.25 to 2.5 mg orally every 6 to 8 hours when clearance is under 30 mL/min, use as needed rather than on a regular schedule, and monitor for sedation and respiratory rate.

• Oxycodone (opioid naive, clearance under 30): 2.5 mg orally every 6 hours as needed, increased slowly.

• Hydromorphone: 0.5 to 1 mg orally every 6 hours as needed, increased slowly.

• Fentanyl: transdermal 12 micrograms/h only for patients already tolerant to opioids. For acute use, intravenous 25 to 50 micrograms with monitoring.

• Buprenorphine transdermal: 5 micrograms/h patch changed every 7 days, no renal adjustment.

• Tramadol: 50 to 100 mg every 12 hours, maximum 200 mg daily when clearance is under 30. Avoid modified release.

• Gabapentin and pregabalin: use the renal bands for the clearance, such as gabapentin 200 to 700 mg once daily at 15 to 29 mL/min.

• Amitriptyline: 10 mg at night, increased slowly.

Monitoring. Review sedation score, respiratory rate, bowel function and pain at each dose change. Co-prescribe a laxative. Reassess when function changes.

Stop rules. Stop the opioid for sedation, respiratory rate under 10 breaths each minute, myoclonus or confusion, and reverse with naloxone 0.4 mg intravenously in small repeated doses if breathing is depressed.

Referral and escalation. Seek palliative or pain specialist advice for pain not controlled on two opioids, for dialysis patients needing regular opioids, and for neuropathic pain.

Common errors. Prescribing morphine or codeine regularly, using NSAIDs for gout or musculoskeletal pain, skipping a laxative, and giving full gabapentin doses.