SN7 SHORT NOTE 5M

Write a short note on sedative-hypnotic poisoning (barbiturates and benzodiazepines).

General Medicine · Final Professional

Introduction

Sedative-hypnotics are among the commonest agents in deliberate self-poisoning, usually taken with alcohol or other central depressants, which greatly increases lethality. Benzodiazepines have largely replaced barbiturates in clinical use, and barbiturate poisoning is now uncommon — but barbiturates remain far more dangerous, with a narrow therapeutic index and a high case fatality.

Mechanism

Both act on the GABA-A receptor, the principal inhibitory receptor of the central nervous system, but differently — and this difference explains their relative toxicity:

Benzodiazepines increase the frequency of chloride channel opening; they require GABA to be present, so their effect has a ceiling.
Barbiturates increase the duration of chloride channel opening and, at high doses, open the channel directly without GABA. There is therefore no ceiling effect, and progressive dosing leads to profound CNS and respiratory depression.

Clinical Features

Feature	Benzodiazepines	Barbiturates
Consciousness	Drowsiness, slurred speech, ataxia; coma uncommon with the drug alone	Deep coma, often prolonged
Respiration	Mild depression; severe only with co-ingestants (alcohol, opioids) or in the elderly and those with lung disease	Marked respiratory depression — the usual cause of death
Cardiovascular	Usually stable	Hypotension from myocardial depression and vasodilatation
Pupils	Normal or slightly small	Small, then may dilate in deep coma
Reflexes	Depressed	Absent; may mimic brain death with a flat EEG
Temperature	Normal	Hypothermia — characteristic
Skin	Normal	"Barbiturate blisters" — bullae over pressure points
Other	Anterograde amnesia	Absent bowel sounds, gastric stasis

Complications: aspiration pneumonia, hypoxic brain injury, pressure necrosis and rhabdomyolysis with compartment syndrome from prolonged immobility, hypothermia, and acute kidney injury.

Investigations

Capillary blood glucose immediately in any unconscious patient.
Arterial blood gas — respiratory acidosis; pulse oximetry and continuous monitoring.
Urine toxicology screen — qualitative only, and frequently negative for clonazepam, lorazepam, alprazolam and newer agents, so a negative screen does not exclude poisoning.
Serum barbiturate level where available, which correlates reasonably with severity.
Paracetamol and salicylate levels — mixed overdose is common and must be excluded.
Electrolytes, renal and liver function, creatine kinase, ECG, chest X-ray for aspiration, and CT head where trauma or focal signs are present.

Management

Supportive care is the mainstay, and good supportive care alone gives excellent outcomes.

Airway, breathing, circulation — the priority. Position, suction, high-flow oxygen; intubate and ventilate for inadequate ventilation or an unprotected airway.
Circulatory support — intravenous fluids for hypotension; vasopressors if fluid alone is insufficient, particularly in barbiturate poisoning.
Rewarming for hypothermia; pressure area care; monitor for rhabdomyolysis with fluids and urine output.
Activated charcoal if presented early with a protected airway; repeated doses enhance elimination of phenobarbitone (enterohepatic recirculation).
Urinary alkalinisation with sodium bicarbonate increases elimination of phenobarbitone (a weak acid) — not useful for short-acting barbiturates or benzodiazepines.
Haemodialysis for severe phenobarbitone poisoning with refractory hypotension, prolonged coma or renal failure.
Flumazenil — a specific benzodiazepine antagonist, but its use is highly restricted (see below).
Psychiatric assessment for all deliberate ingestions before discharge.

DANGER / REMEMBER

Flumazenil is rarely indicated and can be dangerous. In a patient who is benzodiazepine-dependent, or who has co-ingested a tricyclic antidepressant or other pro-convulsant, reversal removes the seizure threshold protection and can precipitate status epilepticus and arrhythmia that are then extremely difficult to treat. Its half-life is also shorter than most benzodiazepines, causing re-sedation. Reserve it for iatrogenic over-sedation from a known single benzodiazepine in a non-dependent patient. In deliberate mixed overdose, manage the airway instead.

NEEDS VERIFICATION

Flumazenil dosing and the precise indications for haemodialysis in phenobarbitone poisoning — confirm against current toxicology guidance.

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