Serotonin syndrome in ICU — FFICM MCQ

Correct answer: D — Serotonin syndrome

The correct answer is D, serotonin syndrome. This patient has recent exposure to two serotonergic agents, sertraline and linezolid (a weak, reversible monoamine oxidase inhibitor), and presents with the classic triad of neuromuscular excitability (inducible clonus, hyperreflexia), autonomic instability (fever, diarrhoea, dilated pupils) and altered mental state (agitation), all developing rapidly within 24 hours of starting linezolid. This rapid onset and the presence of clonus and hyperreflexia (neuroexcitatory signs) rather than rigidity are the discriminating features that point to serotonin toxicity rather than other hyperthermic syndromes. Rising creatine kinase reflects ongoing excessive muscular activity from clonus and myoclonus, a recognised complication of serotonin syndrome. Why the other options are wrong: E. Neuroleptic malignant syndrome: this typically evolves over days rather than hours, and features lead-pipe rigidity with hyporeflexia rather than clonus and hyperreflexia, and there is no antipsychotic exposure in the history. C. Malignant hyperthermia: this is triggered by volatile anaesthetics or suxamethonium, none of which are mentioned; it causes rigidity and hypercarbia rather than clonus and diarrhoea. A. Anticholinergic poisoning: dilated pupils occur but skin is typically dry and flushed, bowel sounds are absent (not diarrhoea), and reflexes are normal rather than hyperreflexic with clonus. B. Opioid withdrawal: causes diarrhoea, agitation and dilated pupils but does not cause hyperreflexia, clonus or a rising creatine kinase, and there is no history of opioid dependence. Key point: linezolid has clinically significant MAO-inhibitory activity, so combining it with sertraline can precipitate serotonin syndrome, distinguished from neuroleptic malignant syndrome by rapid onset, clonus and hyperreflexia rather than rigidity.

Reference: NHS Right Decisions (Scotland), Linezolid Monitoring and Screening Guide, 2023: linezolid interacts with serotonergic agents (SSRIs, SNRIs, MAOIs) with risk of serotonin syndrome, requiring avoidance where possible or close monitoring - https://www.rightdecisions.scot.nhs.uk/media/le2puufa/linezolid-monitoring-and-screening-guide-20230426.pdf