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Benzodiazepine Withdrawal in ICU — FRCA Final MCQ

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ModerateIntensive Care MedicineBenzodiazepine Withdrawal in ICUFRCA Final

A 55-year-old woman has received a continuous high-dose midazolam infusion for 7 days during mechanical ventilation for severe ARDS. During weaning, the infusion rate is reduced rapidly. Within hours she develops marked anxiety, agitation, diffuse tremor, tachycardia and a brief generalised tonic-clonic seizure. Analgesia is adequate, blood glucose and electrolytes are normal, and she has no history of alcohol dependence. What is the most likely diagnosis?

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Correct answer: B — Iatrogenic benzodiazepine withdrawal

The diagnosis is iatrogenic benzodiazepine withdrawal. Prolonged midazolam exposure can produce physical dependence, with risk increasing with dose and duration. Rapid dose reduction removes benzodiazepine-mediated enhancement of inhibitory GABA-A signalling from an adapted CNS, causing rebound excitation and sympathetic activation. The close temporal relationship to weaning, together with anxiety, agitation, tremor, tachycardia and a generalised seizure, is characteristic. Midazolam should therefore be reduced gradually rather than stopped abruptly. Inadequate sedation or pain may cause agitation and tachycardia but do not adequately explain the tremor and seizure. Alcohol withdrawal delirium is unlikely without alcohol dependence. Non-convulsive status epilepticus does not explain the broader withdrawal syndrome and is not itself an overt generalised convulsion.

Reference: electronic Medicines Compendium. Midazolam 5 mg/ml, solution for injection/infusion — Summary of Product Characteristics, sections 4.4 and 4.8 (current version). https://www.medicines.org.uk/emc/product/6420/smpc