Ethanol Toxicity & Alcohol Withdrawal (Delirium Tremens)

A 52-year-old man is admitted 18 hours after his last drink, following a cholecystectomy that ended a chronic 100 g-a-day habit. He is tremulous, agitated, tachycardic (HR 124), hypertensive (180/110), febrile (38.5 degrees C), hallucinating insects crawling on his skin, and disoriented — a CIWA-Ar of 26, with one witnessed generalised tonic-clonic seizure in the emergency department.^[2][5][8]

The clock is already the danger. Up to half of individuals with a history of long-term, heavy alcohol consumption will experience the alcohol withdrawal syndrome when consumption stops — and his syndrome already spans tremor, autonomic activation, perceptual disturbances, seizure and threatened delirium tremens. A history of delirium tremens (likelihood ratio 2.9) or a baseline systolic pressure of 140 mm Hg or higher (LR 1.7) marks the patient at increased likelihood of severe withdrawal. The benzodiazepine is the core; the thiamine protects the brain; escalation agents stand behind the benzodiazepine if he becomes refractory. Every step below hangs on recognising how severe he already is.^[1][2][8]

The pathophysiology — downregulated GABA, upregulated NMDA

Chronic ethanol remodels the brain to hold its inhibition in check — and when the ethanol is withdrawn, the inhibition falls away and the excitation runs unchecked. Ethanol, at concentrations associated with behavioural effects, inhibits the NMDA receptor which mediates the post-synaptic excitatory effects of glutamate; tolerance to ethanol results in up-regulation of the NMDA receptor, and chronic adaptations of both NMDA and GABA receptors occur during intoxication. The pharmacological treatments are cross-tolerant with alcohol for exactly this reason — the benzodiazepines are the agents of choice among cross-tolerant medications.^[3][5][33]

Remove the ethanol and the up-regulated system is unopposed: abrupt withdrawal produces a hyperexcitable state that leads to seizures, delirium tremens, and excitotoxic neuronal death. The human evidence matches the animal story — in the week after cessation, the cerebrospinal fluid of withdrawing patients shows higher aspartate, glycine and N-acetylaspartylglutamate with a lower GABA concentration, and the excitatory neurotransmitters correlate with oxidative-stress markers. This is why the benzodiazepine (restoring GABA tone) and, in refractory disease, the NMDA-antagonist ketamine both make mechanistic sense.^[3][4]

^{[3] [5]}

References33ShowHide

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