38-34: Ethanol, Benzodiazepines, & Other Sedative-Hypnotic Agents Overdose

The group of agents known as sedative-hypnotic drugs includes a variety of products used for the treatment of anxiety, depression, insomnia, and epilepsy. Besides common benzodiazepines, such as lorazepam, alprazolam, clonazepam, diazepam, oxazepam, chlordiazepoxide, and triazolam, this group includes the newer benzodiazepine-like hypnotics zolpidem, zopiclone, and zaleplon, the muscle relaxants baclofen and carisoprodol, and barbiturates such as phenobarbital. Phenibut, a GABA_B agonist, has gained popularity in recent years, and is associated with CNS depression and a withdrawal syndrome. Ethanol and other selected agents are also popular recreational drugs. All of these drugs depress the CNS reticular activating system, cerebral cortex, and cerebellum.

CLINICAL FINDINGS

Mild intoxication produces euphoria, slurred speech, and ataxia. Ethanol intoxication may produce hypoglycemia, even at relatively low concentrations, in children and in fasting adults. With more severe intoxication, stupor, coma, and respiratory arrest may occur. Carisoprodol (Soma) commonly causes muscle jerking or myoclonus. Death or serious morbidity is usually the result of pulmonary aspiration of gastric contents. Bradycardia, hypotension, and hypothermia are common. Patients with massive intoxication may appear to be dead, with no reflex responses and even absent electroencephalographic activity. Diagnosis and assessment of severity of intoxication are usually based on clinical findings. Ethanol serum levels over 300 mg/dL (0.3 g/dL; 65 mmol/L) can produce coma in infrequent drinkers, while regular drinkers may remain awake at much higher levels.

TREATMENT

A. Emergency and Supportive Measures

Administer activated charcoal if the patient has ingested a massive dose and the airway is protected. Repeat-dose charcoal may enhance elimination of phenobarbital, but it has not been proved to improve clinical outcome. Hemodialysis may be necessary for patients with severe phenobarbital intoxication.

B. Specific Treatment

Flumazenil is a benzodiazepine receptor-specific antagonist; it has no effect on ethanol, barbiturates, or other sedative-hypnotic agents. If used, flumazenil is given slowly intravenously, 0.2 mg over 30–60 seconds, and repeated in 0.2–0.5 mg increments as needed up to a total dose of 3–5 mg. Caution: Flumazenil should rarely be used because it may induce seizures in patients with preexisting seizure disorder, benzodiazepine tolerance, or concomitant tricyclic antidepressant or other convulsant overdose. If seizures occur, diazepam and other benzodiazepine anticonvulsants may not be effective. As with naloxone, the duration of action of flumazenil is short (2–3 hours) and resedation may occur, requiring repeated doses.