Sedative-hypnotic agents are widely used for the treatment of insomnia and anxiety. As a group, they are one of the most frequently prescribed medications. Barbiturates, benzodiazepines, antihistamines, skeletal muscle relaxants, antidepressants and anticholinergic agents are discussed elsewhere in this book. Table II-56 lists other or older/outdated hypnotic agents.

The exact mechanism of action and the pharmacokinetics (see also Table II-63,) vary for each agent. The major toxic effect that causes serious poisoning or death is CNS depression resulting in coma, respiratory arrest, and pulmonary aspiration of gastric contents.

The toxic dose varies considerably between drugs and also depends largely on individual tolerance and the presence of other drugs, such as alcohol. For chloral hydrate and meprobamate, ingestion of 3-5 times the usual hypnotic dose may result in coma. However, co-ingestion of alcohol or other drugs may cause coma after smaller ingestions, whereas individuals who chronically use large doses of these drugs may tolerate much higher acute doses. The newer melatonin agonists ramelteon and tasimelteon and the orexin receptor antagonists lemborexant and suvorexant are safer.

Overdose with many of these drugs may cause drowsiness, ataxia, nystagmus, stupor, coma, and respiratory arrest. Deep coma may result in absent reflexes, fixed pupils, and depressed or absent electroencephalographic (EEG) activity. Hypothermia may occur. Hypotension with a large overdose is caused primarily by depression of cardiac contractility and, to a lesser extent, loss of venous tone.

1. Chloral hydrate is metabolized to trichloroethanol, which also has CNS-depressant activity. In addition, trichloroethanol may sensitize the myocardium to the effects of catecholamines, resulting in cardiac arrhythmias.
2. Buspirone may cause nausea, vomiting, drowsiness, and miosis. There have been no reported deaths.
3. Glutethimide often produces mydriasis (dilated pupils) and other anticholinergic side effects, and patients may exhibit prolonged and cyclic or fluctuating coma. Glutethimide sometimes is taken in combination with codeine (“loads”), which may produce opioid effects.
4. Meprobamate has been reported to form tablet concretions in large overdoses, occasionally requiring surgical removal. Hypotension is more common with this agent than with other sedative-hypnotics. Meprobamate is the metabolite of the skeletal muscle relaxant carisoprodol.
5. Methaqualone is unusual among sedative-hypnotic agents in that it frequently causes muscular hypertonicity, clonus, and hyperreflexia. The skeletal muscle relaxant carisoprodol also frequently causes increased muscle tone and myoclonus.
6. Ramelteon and tasimelteon are melatonin receptor agonists. They may cause mild CNS depression. There have been no reported deaths.
7. Lemborexant and suvorexant are orexin receptor antagonists. They are expected to cause CNS depression. There have been no reported deaths.

Usually is based on a history of ingestion because clinical manifestations are fairly nonspecific. Hypothermia and deep coma may mimic death; thus, careful evaluation should precede the diagnosis of brain death. Chloral hydrate is radiopaque and may be visible on plain abdominal radiographs.

1. Specific levels and qualitative urine screening are usually available through commercial toxicology laboratories but are rarely of value in emergency management.
   1. Drug levels do not always correlate with severity of intoxication, especially in patients who have tolerance to the drug or have also ingested other drugs or alcohol. In addition, early after ingestion, blood levels may not reflect brain concentrations.
   2. Levels of chloral hydrate's active metabolite trichloroethanol may correlate better with the state of intoxication.
2. Other useful laboratory studies include electrolytes, glucose, serum ethanol, BUN, creatinine, arterial blood gases, ECG, and chest radiography.

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary. Administer supplemental oxygen.
   2. Treat coma, hypothermia, hypotension, and pulmonary edema if they occur.
   3. Monitor patients for at least 6 hours after ingestion because delayed absorption may occur. Patients with chloral hydrate ingestion should be monitored for at least 18-24 hours because of the risk for cardiac arrhythmias. Tachyarrhythmias caused by myocardial sensitization may be treated with propranolol, 1-2 mg IV, or esmolol, 0.025-0.1 mg/kg/min IV.
2. Specific drugs and antidotes. None. Flumazenil is a specific antagonist of benzodiazepine receptors, but it is not effective for the drugs listed in this chapter.
3. Decontamination . Administer activated charcoal orally if conditions are appropriate (see Table I-37,). Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly.
4. Enhanced elimination. Because of extensive tissue distribution, dialysis and hemoperfusion are not very effective for most of the drugs in this group.
   1. Repeat-dose charcoal may enhance elimination of glutethimide (which undergoes enterohepatic recirculation) and meprobamate, although no studies have been performed to document clinical effectiveness.
   2. Meprobamate has a relatively small volume of distribution (0.7 L/kg), and hemodialysis or continuous renal replacement therapy (CRRT) may be useful for deep coma complicated by intractable hypotension.