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Toxicity, Benzodiazepine: Treatment & Medication
Updated: Jul 29, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
- Cardiac monitoring
- Supplemental oxygen
- Intravenous access
- Rapid glucose determination
- Naloxone, if the diagnosis is unclear or an opiate co-ingestion is suspected
Emergency Department Care
Continue supportive care and monitoring (eg, cardiac monitoring, IV, oximetry, vital signs).
- Decontamination
- Ipecac syrup is contraindicated for prehospital or hospital use because of the risk for CNS depression and subsequent aspiration with emesis.
- Gastric lavage is not recommended but may be considered if the presence of a lethal co-ingestant is suspected and the patient presents within 1 hour of ingestion.
- Single-dose activated charcoal is recommended for GI decontamination in patients who present within 4 hours of ingestion or in symptomatic patients when the time of ingestion is unknown.
- Respiratory depression may be treated with assisted ventilation.
The American Psychiatric Association and the National Institute of Clinical Excellence have treatment and diagnostic guidelines available for cases of substance abuse and self-harm.2,3
Consultations
- Toxicologist or a poison control center
- Intensive care specialist
- Psychiatrist, if suicide attempt
Medication
GI decontaminant
Empirically used to minimize systemic absorption of the toxin.
Activated charcoal (Liqui-Char)
Most useful if administered within 1-2 h of ingestion. Repeat doses may be used, especially with ingestion of sustained release agents. Limited outcome studies exist, especially when administration is more than 1 h of ingestion.
Administration of charcoal by itself (in aqueous solution), as opposed to coadministration with a cathartic is becoming the current practice standard. Studies have not shown benefit from cathartics, and, while most drugs and toxins are absorbed within 30-90 min, laxatives take hours to work. Dangerous fluid and electrolyte shifts have occurred when cathartics are used in small children.
When the ingested dose is known, charcoal may be administered at 10 times ingested dose of agent over 1 or 2 doses.
Adult
1 g/kg PO/NG (typically 50-75 g); cathartic optional but not routinely recommended; repeat dose of 0.5 g/kg PO/NG if desired; do not use cathartic with repeat doses
Pediatric
Administer as in adults (typically 12.5-25 g); avoid cathartic in children <2 y
May inactivate ipecac syrup if used concomitantly; effectiveness of other medications decreases with coadministration; do not mix with sherbet, milk, or ice cream (decreases absorptive properties)
Documented hypersensitivity; poisoning or overdose of mineral acids and alkalies; unprotected airway with absent gag reflex
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
Protect airway before administration in patients with absent gag reflex or a depressed level of consciousness; when considering repeat dosing, monitor for active bowel sounds to minimize risk of charcoal ileus; not very effective in poisonings of ethanol, methanol, and iron salts; induce emesis before administering activated charcoal; after emesis with ipecac, 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
Flumazenil is a selective competitive antagonist of the GABA receptor and the only available specific antidote for BZDs; it will reverse effects of BZDs but must be used with caution. If BZDs are being used to treat a potentially life-threatening condition (eg, seizure disorder), antagonists may exacerbate the underlying disorder.
Additionally, co-ingestion commonly occurs with agents that lower the seizure threshold (eg, cyclic antidepressants) and reversal may result in seizure or status epilepticus; therefore, antagonists are not recommended for use by prehospital personnel or for indiscriminate use before a complete evaluation.
In overdose situations, flumazenil may be used for patients with pure BZD overdose who are verbally unresponsive and have no history of long-term BZD use or seizure disorder. Perform an ECG should be performed before use to confirm the absence of cardiac conduction disturbances (which would suggest the presence of cyclic antidepressants). Use as a diagnostic and therapeutic agent for unsubstantiated drug-associated coma is controversial. A positive response to small titratable doses may obviate the need for endotracheal (ET) intubation and the search for other causes of coma.
Flumazenil (Romazicon)
DOC to reverse effects of BZDs in an overdose by selectively antagonizing GABA/BZD receptor complex.
If overdosed patient has not responded after 5 min of 5 mg cumulative dose, cause of sedation is not likely to be BZDs.
Adult
0.1-0.2 mg IV q1min to a total dose of 1 mg at one time or 3 mg in 1 h; infusion rates of 0.1 mg/min decrease disconcerting rapid arousal
Pediatric
0.002-0.02 mg/kg IV q1min
Caution with mixed drug overdose; toxic effects due to other drugs taken in overdose (eg, cyclic antidepressants) may occur with reversal of BZD effects
Documented hypersensitivity; serious cyclic-antidepressant overdosage; patients using BZDs to control a potentially life-threatening condition (eg, intracranial pressure, status epilepticus); chronic BZD use
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studies in humans; may use if benefits outweigh risk to fetus
Precautions
Patients on BZDs for prolonged periods may experience seizures; monitor for resedation and unmasking of seizures
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| Differential Diagnoses & Workup: Toxicity, Benzodiazepine |
 Treatment & Medication: Toxicity, Benzodiazepine |
| Follow-up: Toxicity, Benzodiazepine |
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References
Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). 2008;46:927 - 1057. [Medline]. [Full Text].
[Guideline] Kleber HD, Weiss RD, Anton RF, et al. Treatment of patients with substance use disorders, second edition. American Psychiatric Association. Am J Psychiatry. Aug 2006;163(8 Suppl):5-82. [Medline]. [Full Text].
[Guideline] National Collaborating Centre for Mental Health. Self-harm: the short-term physical and psychological management and secondary prevention of self-harm in primary and secondary care. London (UK): National Institute for Clinical Excellence (NICE). 2004;199. [Full Text].
Bosse GM. Benzodiazepines. In: Emergency Medicine: A Comprehensive Study Guide. 4th ed. McGraw-Hill; 1996:759-61.
Buckley NA, Dawson AH, Whyte IM, O'Connell DL. Relative toxicity of benzodiazepines in overdose. BMJ. Jan 28 1995;310(6974):219-21. [Medline].
Cairns C. Benzodiazepine overdose and withdrawal. In: Emergency Medicine: Concepts and Clinical Practice. 3rd ed. Mosby-Year Book; 1992:2684-9.
Drummer OH, Syrjanen ML, Cordner SM. Deaths involving the benzodiazepine flunitrazepam. Am J Forensic Med Pathol. Sep 1993;14(3):238-43. [Medline].
Hoffman RS, Wipfler MG, Maddaloni MA, Weisman RS. Has the New York State triplicate benzodiazepine prescription regulation influenced sedative-hypnotic overdoses?. N Y State J Med. Oct 1991;91(10):436-9. [Medline].
Lai MW, Klein-Schwartz W, Rodgers GC, Abrams JY, Haber DA, Bronstein AC. 2005 Annual Report of the American Association of Poison Control Centers' national poisoning and exposure database. Clin Toxicol (Phila). 2006;44(6-7):803-932. [Medline].
Longmire AW, Seger DL. Topics in clinical pharmacology: flumazenil, a benzodiazepine antagonist. Am J Med Sci. Jul 1993;306(1):49-52. [Medline].
Mullins ME. First-degree atrioventricular block in alprazolam overdose reversed by flumazenil. J Pharm Pharmacol. Mar 1999;51(3):367-70. [Medline].
Verghese J, Merino J. Temazepam overdose associated with bullous eruptions. Acad Emerg Med. Oct 1999;6(10):1071. [Medline].
Further Reading
Keywords
BZD toxicity, sedative-hypnotic toxicity, benzodiazepine toxicity, benzodiazepine treatment, flumazenil, benzodiazepine exposure, BZD exposure, seizure control, anxiety, alcohol withdrawal, insomnia, control of drug-associated agitation, muscle relaxants, preanesthetic agents, BZD overdose, nystagmus, amnesia, paradoxical agitation, respiratory depression, hypotension, alprazolam, flunitrazepam, chlordiazepoxide, diazepam, triazolam, temazepam, flurazepam, bromazepam, clorazepate, oxazepam, nitrazepam, loprazolam, lormetazepam, lorazepam, benzodiazepine overdose
