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CBRNE - Incapacitating Agents, Opioids/Benzodiazepines: Treatment & Medication

Author: Christopher P Holstege, MD, Associate Professor of Emergency Medicine and Pediatrics, University of Virginia; Director, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Ctr, Associate Medical Toxicology Fellowship Director, VA Dept of Health
Coauthor(s): Jennifer S Boyle, MD, PharmD, Fellow in Toxicology, University of Virginia Health System
Contributor Information and Disclosures

Updated: Feb 5, 2009

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

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

References

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  7. Brooks M. Knockout gas: Chemical weapons in disguise?. New Scientist. October 2007;[Full Text].

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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

Contributor Information and Disclosures

Author

Christopher P Holstege, MD, Associate Professor of Emergency Medicine and Pediatrics, University of Virginia; Director, Division of Medical Toxicology, Center of Clinical Toxicology; Medical Director, Blue Ridge Poison Ctr, Associate Medical Toxicology Fellowship Director, VA Dept of Health
Christopher P Holstege, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American Academy of Emergency Medicine, American Association for the Advancement of Science, American College of Emergency Physicians, American College of Medical Toxicology, American Medical Association, Medical Society of Virginia, Society for Academic Emergency Medicine, Society of Toxicology, and Wilderness Medical Society
Disclosure: Nothing to disclose.

Coauthor(s)

Jennifer S Boyle, MD, PharmD, Fellow in Toxicology, University of Virginia Health System
Disclosure: Nothing to disclose.

Medical Editor

Suzanne White, MD, Medical Director, Regional Poison Control Center at Children's Hospital, Program Director of Medical Toxicology, Associate Professor, Departments of Emergency Medicine and Pediatrics, Wayne State University School of Medicine
Suzanne White, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Clinical Toxicology, American College of Epidemiology, American College of Medical Toxicology, American Medical Association, and Michigan State Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Rick Kulkarni, MD, Medical Director, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Robert G Darling, MD, FACEP, Clinical Assistant Professor of Military and Emergency Medicine, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Director, Center for Disaster and Humanitarian Assistance Medicine
Robert G Darling, MD, FACEP is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, and Association of Military Surgeons of the US
Disclosure: Nothing to disclose.

 
 
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