Renal Failure Drug Adjustments — FRCA Final MCQ

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ModerateGeneral AnaesthesiaRenal Failure Drug AdjustmentsFRCA Final

A 72-year-old man (ASA III) with chronic kidney disease (eGFR 22 mL/min/1.73 m²) requires general anaesthesia for an emergency laparotomy. Postoperative analgesia and neuromuscular blockade are being planned. Which drug is most likely to cause clinically important prolonged sedation and respiratory depression through accumulation of a renally eliminated active metabolite, and therefore requires dose reduction or avoidance?

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Correct answer: C — Morphine

C. Morphine is glucuronidated hepatically to morphine-3-glucuronide and morphine-6-glucuronide (M6G). These metabolites are cleared by the kidneys, and the UK SmPC warns that M6G accumulates in renal failure causing CNS and respiratory depression, so dosage should be reduced or morphine avoided with close monitoring. Remifentanil is hydrolysed by non-specific blood and tissue esterases; its carboxylic acid metabolite is essentially inactive and the SmPC states no dose adjustment is needed in renal impairment or renal replacement therapy — the commonest distractor because that metabolite does accumulate. Atracurium is eliminated by Hofmann degradation and ester hydrolysis, independent of renal function (laudanosine accumulation is not clinically significant at usual doses). Propofol is cleared by hepatic and extrahepatic conjugation to inactive metabolites, and desflurane is minimally metabolised and eliminated unchanged by the lungs.

Reference: Electronic Medicines Compendium (eMC), Morphine Sulfate 10mg/5ml Oral Solution — Summary of Product Characteristics, sections 4.2/4.4 (renal impairment; morphine-6-glucuronide accumulation), current version accessed 2025: https://www.medicines.org.uk/emc/product/2629/smpc