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Toxicity, Sedative-Hypnotics: Treatment & Medication
Updated: Dec 10, 2007
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
- Establish ABCs, obtain IV access, provide oxygen, and perform aggressive supportive care with airway protection as necessary.
- Ipecac syrup is not recommended for home use because of the fear of emesis after onset of respiratory depression.
- Ensure adequate airway and ventilation. Consider and reassess the need for endotracheal intubation.
Emergency Department Care
- General
- Given that the major issues in an overdose are aspiration, respiratory depression or failure, hypoxia, hypotension, and cardiac arrhythmias, the most important aspects in managing an overdose situation are, as usual, the ABCs — airway, breathing, and circulation.
- Prevention of absorption
- Gastric lavage may be performed if the patient presents obtunded within 1 hour of ingestion or rapidly deteriorates while in the emergency department. The airway should be secured in such instances prior to gastric intubation and lavage.
- The use of activated charcoal has become debated, and its liberal use is discouraged. In general, measures to prevent absorption (eg, emesis, gastric lavage) or increase excretion (eg, diuresis, catharsis) of the drug have not been shown consistently to reduce mortality associated with drug toxicity. Considerable morbidity is associated with charcoal aspiration. Its use should be limited to substances that would be well absorbed and have a high likelihood of toxic dose ingestion.
- It is not recommended in instances in which GHB or GBL are known to be the only intoxicants.
- Multi-dose activated charcoal (20-50 g q4h) is recommended for overdoses with barbiturates, glutethimide, and meprobamate.
- Elimination enhancement
- Alkaline diuresis enhances elimination of phenobarbital and other long-acting barbiturates. It is recommended for all symptomatic patients with long-acting barbiturate toxicity.
- Consider hemodialysis or hemoperfusion in glutethimide, methyprylon, phenobarbital, meprobamate, and chloral hydrate poisoning.
- Flumazenil
- Flumazenil competitively and reversibly binds benzodiazepine receptors (ie, GABA).
- The use of flumazenil for suspected benzodiazepine overdoses is controversial. Some sources would go so far as to suggest that flumazenil has no role in the routine treatment of a coma unless the patient is known not to be benzodiazepine dependent and the overdose is known to result only from benzodiazepines. If used, flumazenil should be administered slowly (0.2 mg/min up to 3-5 mg) because large doses cause agitation and withdrawal. Serious risk of inducing seizures exists, particularly in patients with co-ingestions or long-term use of benzodiazepines.
- This drug is contraindicated in patients with increased intracranial pressure (ICP) or closed head injury (CHI), those with a history of epilepsy, or those known to have ingested a tricyclic antidepressant (TCA) agent.
- Meprobamate
- Forced diuresis
- Hemodialysis in severe intoxication
- Whole bowel irrigation (recommended for serious meprobamate poisoning because of the high predilection for bezoar formation)
- Methaqualone (Quaalude)
- No diuresis
- Diazepam for severe tonicity or seizures (strongly consider phenytoin as an anticonvulsant because barbiturates potentiate this drug)
- Chloral hydrate
- Lidocaine may be used for ventricular dysrhythmias.
- Beta-blockers (eg, propranolol) and overdrive pacing have also been reported to be effective. Intravenous propranolol is, perhaps, the drug of choice for chloral hydrate-associated ventricular dysrhythmias. Chloral hydrate sensitizes the myocardium to catecholamines, and propranolol blocks this effect.
- Strongly avoid beta-adrenergic agonists (eg, dopamine) because they increase risk of fatal dysrhythmias.
- Consider hemodialysis.
Consultations
Consider a consultation with a toxicologist and psychiatrist.
Medication
The only available antidotelike drug is flumazenil for benzodiazepine intoxication. Use of flumazenil in intentional drug overdose of unknown etiology is not cost effective or particularly prudent and is not encouraged. All other therapy is supportive or designed to limit absorption or enhance elimination.
GI decontaminant
Empirically used to minimize systemic absorption of the toxin. May only be of benefit if administered within 1-2 h of ingestion.
Activated charcoal (Liqui-Char)
Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
For maximum effect, administer within 30 min of ingesting poison. The initial dose may be given with water or a cathartic (such as 70% sorbitol). Sorbitol should not be given to children <2 y.
Adult
1 g/kg (50-100 g) PO
Pediatric
Administer as in adults (usually 15-30 g)
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases adsorptive properties)
Documented hypersensitivity; poisoning or overdose of mineral acids and alkalies; unprotected airway
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor for presence of bowel sounds to minimize risk of charcoal ileus; not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before administration; after emesis with ipecac syrup, patient may not tolerate activated charcoal for 1-2 h; can administer in early stages of gastric lavage; without sorbitol, gastric lavage returns are black
Antagonist
Reverses benzodiazepine sedation and respiratory depression.
Flumazenil (Romazicon)
Competitively and reversibly binds benzodiazepine receptors (GABA). Administer slowly; large doses cause agitation and withdrawal.
Usually effective after 0.4-1 mg. Although up to 3-5 mg in massive ingestions have been required.
In cases of resedation, IV drip at 0.01-0.05 mg/kg/h may be used. Only consider a flumazenil drip if the patient is not habituated to sedative-hypnotic agents.
Adult
0.2 mg IV qmin; not to exceed 3-5 mg
Pediatric
0.01 IV mg/kg; not to exceed 0.05 mg/kg
Caution in cases of mixed drug overdose; toxic effects from other drugs taken in overdose (eg, cyclic antidepressants) may occur with reversal of benzodiazepine effects by flumazenil
Documented hypersensitivity; serious cyclic-antidepressant overdose; patients given a benzodiazepine for control of potentially life-threatening condition (eg, intracranial pressure, status epilepticus)
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
May precipitate seizures or withdrawal reactions; duration of action often less than benzodiazepine, requiring repeated dosing and close patient monitoring
More on Toxicity, Sedative-Hypnotics |
| Overview: Toxicity, Sedative-Hypnotics |
| Differential Diagnoses & Workup: Toxicity, Sedative-Hypnotics |
 Treatment & Medication: Toxicity, Sedative-Hypnotics |
| Follow-up: Toxicity, Sedative-Hypnotics |
| References |
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References
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Further Reading
Keywords
sedative-hypnotic exposure, sedative-hypnotic toxicity, sedative-hypnotic poisoning, sedative-hypnotic overdose, CNS depression, benzodiazepines, barbiturates, nonbarbiturate nonbenzodiazepine sedative hypnotics, buspirone, zolpidem, ethchlorvynol, glutethimide, chloral hydrate, meprobamate, methaqualone, methyprylon, carisoprodol, gamma-hydroxybutyrate, GHB, gamma-butyrolactone, GBL, GABA, flumazenil, Quaalude, methohexital, Brevital, thiopental, Pentothal, amobarbital, Amytal, pentobarbital, Nembutal, secobarbital, Seconal, butalbital, Fioricet, Fiorinal, carbamates, meprobamate, Miltown, chloral derivatives, Noctec, ethchlorvynol, Placidyl, piperidines, glutethimide, Doriden, methyprylon, Noludar, quinazolinone, methaqualone, imidazopyridine, zolpidem, Ambien, alpidem, diphenhydramine, doxylamine
