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CBRNE - Incapacitating Agents, Opioids/Benzodiazepines: Treatment & Medication
Updated: Feb 5, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
Prehospital care providers must place their personal safety before the treatment of patients who may be contaminated with an incapacitating agent. Emergency responders should not enter a contaminated location that has not been secured. Little is known regarding the risk of secondary contamination in health care providers exposed to patients with contamination from opioid or benzodiazepine aerosolized agents.
- For civilian paramedics, exposed patients must be decontaminated prior to transfer. Absorption and subsequent toxicity is a risk from contact with patients who have been contaminated. Paramedics are at increased risk for toxicity in the closed confines of an ambulance. Caution must be exercised, especially for flight crews, because toxicity of the pilot during flight can lead to impaired judgment and subsequent risk of crashing the aircraft.
- Initiation of intravenous access and the infusion of intravenous fluids should be considered. Before intubation, naloxone may be administered intravenously to patients with respiratory compromise and suspected opioid. Aggressive airway control must take precedence over pharmacologic reversal because the vast majority of morbidity and mortality results from respiratory depression.
Emergency Department Care
Once decontamination has occurred, the primary emphasis is simply supportive care of exposed patients. Emergency department staff must be certain that proper decontamination has occurred. Aerosolization of the agents from contaminated patients may occur and can pose a risk to hospital personnel.
- Airway protection is paramount. In patients who present with coma, aspiration is a risk if adequate airway protection is not achieved. Hypoglycemia should be considered in all patients presenting with altered mental status and glucose administered when necessary. Naloxone may be infused in an attempt to reverse opioid activity (see Medication). Naloxone has an excellent safety record and is standard therapy in many institutions as part of the so-called coma cocktail. Flumazenil may be considered with caution because a number of contraindications exist in its use (see Medication). Thiamine administration should be considered in patients presenting with altered mental status.
- Intravenous hydration may be necessary; maintain adequate urinary output. Consider placement of a Foley catheter to monitor the patient's urine output.
- Include continuous cardiac monitoring in patients who are symptomatic.
Consultations
If an exposure to aerosolized benzodiazepines or opioids occurs, consider a number of consultations.
- Medical toxicologists: Consider consulting these physicians early to assist in the diagnosis and appropriate treatment of patients with possible exposure to these aerosolized agents.
- Critical care specialists: For patients requiring intensive care monitoring, consider early consultation with a physician trained in critical care medicine.
- Law enforcement: If the cause of the exposure is a terrorist act against civilians, immediately contact the local law enforcement agency, health department, and poison control center. Also, contact federal agencies, such as the US Federal Bureau of Investigations (FBI).
Medication
If patients present following exposure to aerosolized opioids or benzodiazepines, administration of the competitive antagonists naloxone and flumazenil, respectively, may be considered to reverse respiratory depression and coma.
Opioid antagonists
Opioid antagonists competitively inhibit the binding of opioid agonists to the opioid receptors. The goal of this therapy is reinstitution of adequate spontaneous ventilation. In patients presenting with sedation of unknown etiology, the cautious administration of naloxone may be both diagnostic and therapeutic. Even in high doses, naloxone has an excellent safety profile.
Naloxone (Narcan)
DOC of opioid antagonists because of relatively short half-life, safety record, and availability.
Adult
0.4-2 mg IV/IM/SC q2-3min prn; use increments of 0.1-0.2 mg in opioid dependency; may need to repeat dose q20-60min
Question diagnosis if no response seen after administering 10 mg
Pediatric
0.1 mg/kg IV/IM/SC; repeat q2-3min prn
Decreases analgesic effects of narcotics
Documented hypersensitivity
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 withdrawal symptoms in opiate addiction
Benzodiazepine antagonists
Flumazenil is a competitive benzodiazepine antagonist that reverses the effects of benzodiazepines. However, benzodiazepine agonists must be used with caution because, when used to treat a potentially life-threatening condition (eg, seizure disorder), they may exacerbate the underlying disorder. If a patient ingests a drug that lowers the seizure threshold, such as a cyclic antidepressant, reversal may result in seizure or status epilepticus. Flumazenil is not recommended for indiscriminate use before a complete evaluation. If patients present with coma following aerosolized benzodiazepines exposure, flumazenil may be considered if the patient has respiratory depression and no history of long-term benzodiazepine use or seizure disorder. 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.
Flumazenil (Romazicon)
Reverses effects of benzodiazepines in overdose by selectively antagonizing benzodiazepine receptor at GABA-A complex.
Adult
0.2 mg IV initially over 30 s; repeat at 1-min intervals with 0.5 mg over 30 s until satisfactory response attained or 3 mg given
Dose may require additional titration
Pediatric
0.01 mg/kg IV initially over 15 s; repeat at 1-min intervals with 0.005-0.01 mg/kg
Caution in cases of mixed drug overdose; concurrent use with other drugs taken in overdose (eg, cyclic antidepressants) may cause toxic effects
Documented hypersensitivity; overdosage of potential seizure-producing drugs; long-term benzodiazepine use (may cause potentially life-threatening withdrawal); seizures
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
Seizures may occur in patients with history of prolonged benzodiazepine use (benzodiazepine-dependent) or in setting of mixed substance exposure, where effects of benzodiazepines are abruptly reversed
Resedation may occur
More on CBRNE - Incapacitating Agents, Opioids/Benzodiazepines |
| Overview: CBRNE - Incapacitating Agents, Opioids/Benzodiazepines |
| Differential Diagnoses & Workup: CBRNE - Incapacitating Agents, Opioids/Benzodiazepines |
Treatment & Medication: CBRNE - Incapacitating Agents, Opioids/Benzodiazepines |
| Follow-up: CBRNE - Incapacitating Agents, Opioids/Benzodiazepines |
| References |
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References
Stone A. Chemical weapons. U.S. research on sedatives in combat sets off alarms. Science. Aug 2 2002;297(5582):764. [Medline].
Hess L, Schreiberova J, Fusek J. Pharmacological non-lethal weapons. 3rd European Symposium on Non-Lethal Weapons. May 10-12, 2005. Available at http://www.non-lethal-weapons.com/sy03abstracts/V23.pdf. Accessed January 10, 2009.
Xi LY, Zheng WM, Zhen SM, Xian NS. Rapid arrest of seizures with an inhalation aerosol containing diazepam. Epilepsia. Mar-Apr 1994;35(2):356-8. [Medline].
Hung OR, Whynot SC, Varvel JR, et al. Pharmacokinetics of inhaled liposome-encapsulated fentanyl. Anesthesiology. Aug 1995;83(2):277-84. [Medline].
Wax PM, Becker CE, Curry SC. Unexpected "gas" casualties in Moscow: a medical toxicology perspective. Ann Emerg Med. May 2003;41(5):700-5. [Medline].
Booij LH. [The agent used to free the hostages in Moscow and the insufficient Dutch preparations in case of a terrorist chemical disaster]. Ned Tijdschr Geneeskd. Dec 14 2002;146(50):2396-401. [Medline].
Brooks M. Knockout gas: Chemical weapons in disguise?. New Scientist. October 2007;[Full Text].
Coupland RM. Incapacitating chemical weapons: a year after the Moscow theatre siege. Lancet. Oct 25 2003;362(9393):1346. [Medline].
Enserink M, Stone R. Toxicology. Questions swirl over knockout gas used in hostage crisis. Science. Nov 8 2002;298(5596):1150-1. [Medline].
Gudmundsdottir H, Sigurjonsdottir JF, Masson M, et al. Intranasal administration of midazolam in a cyclodextrin based formulation: bioavailability and clinical evaluation in humans. Pharmazie. Dec 2001;56(12):963-6. [Medline].
Ljungman G, Kreuger A, Andreasson S, et al. Midazolam nasal spray reduces procedural anxiety in children. Pediatrics. Jan 2000;105(1 Pt 1):73-8. [Medline].
Loftsson T, Gudmundsdottir H, Sigurjonsdottir JF, et al. Cyclodextrin solubilization of benzodiazepines: formulation of midazolam nasal spray. Int J Pharm. Jan 5 2001;212(1):29-40. [Medline].
Mather LE, Woodhouse A, Ward ME. Pulmonary administration of aerosolised fentanyl: pharmacokinetic analysis of systemic delivery. Br J Clin Pharmacol. Jul 1998;46(1):37-43. [Medline].
Rieder J, Keller C, Hoffmann G. Moscow theatre siege and anaesthetic drugs. Lancet. Mar 29 2003;361(9363):1131. [Medline].
Schiermeier Q. Hostage deaths put gas weapons in spotlight. Nature. Nov 7 2002;420(6911):7. [Medline].
Weinberger S. Czech Research Stirs Chemical Weapons Debate. October 17, 2007. Wired. Available at http://blog.wired.com/defense/2007/10/czech-research-.html. Accessed January 10, 2009.
Worsley MH, MacLeod AD, Brodie MJ, et al. Inhaled fentanyl as a method of analgesia. Anaesthesia. Jun 1990;45(6):449-51. [Medline].
Further Reading
Keywords
incapacitating agent, opioid, benzodiazepine, fentanyl, carfentanil, alfentanil, sufentanil, diazepam, chemical warfare agents, chemical threat agents, biological threat agents, radiological threat agents, nuclear threat agents, explosive threat agents, chemical weapons, benzodiazepine toxicity, opioid toxicity
Treatment & Medication: CBRNE - Incapacitating Agents, Opioids/Benzodiazepines