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CBRNE - Nerve Agents, Binary - GB2, VX2 Medication

  • Author: Larissa I Velez-Daubon, MD; Chief Editor: Duane C Caneva, MD, MSc  more...
 
Updated: Apr 28, 2015
 

Medication Summary

Table 3 summarizes the different agents used to treat patients with nerve agent poisoning. Table 4 provides some general treatment guidelines.

All but the mildest exposures cause some degree of respiratory compromise. For this reason, oxygen should be readily available. Most of these symptoms are the result of bronchorrhea and bronchoconstriction and improve after appropriate administration of antidotes. Ventilatory support may be needed for severely poisoned patients because of respiratory muscle paralysis. Oxygen is supplied via nasal cannula, face mask, or nonrebreather mask. Remember that inspired oxygen concentrations of 50-100% carry a substantial risk of lung damage when used for more than a few hours.

Table 3. Drugs Used to Treat Patients With Nerve Agent Poisoning* (Open Table in a new window)

DrugDose (Adult)RouteIndicationsContraindications
Atropine2 mg q5-10min prn



Note: The MARK 1 kit contains 2 mg of atropine.



IV/IM/ETTExcessive muscarinic symptomsRelative: IV route in hypoxia has been associated with ventricular fibrillation.
Pralidoxime chloride (Protopam, 2-PAM)15-25 mg/kg over 20 min; can be repeated after 1 h



Note: The MARK 1 kit contains 600 mg of pralidoxime.



IV/IMSymptomatic nerve agent poisoningRapid infusion may result in hypertension; may worsen symptoms in carbamate poisoning
Diazepam (Valium)2-5 mg IV



10 mg IM



IV/IMModerate or severe signs of poisoning, seizuresNone
*Adapted from Sidell, 1992.[3]

Table 4. Summary of Treatment Modalities According to Severity of Exposure* (Open Table in a new window)

Severity/Route of ExposureAtropine (Adult Dose)PralidoximeDiazepamOther
SuspectedNoNoNoDecontamination and 18-h observation for liquid exposures
Mild2 mg for severe



rhinorrhea or



dyspnea; may be



repeated



Administer if dyspnea



is not improving



or if GI



symptoms occur



NoDecontamination and 18-h observation for liquid exposures; oxygen
Moderate6 mg; may need to repeatAdminister with atropineAdminister even in absence of seizuresDecontamination; oxygen
SevereStart with 6 mg; may need to repeatAdminister with atropine; should repeat once or twiceAdminister even in absence of seizuresAirway, breathing, and circulation; decontamination
*Adapted from Sidell, 1992.[3]
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Anticholinergic agents

Class Summary

These agents antagonize ACh at the muscarinic receptor.

Atropine IV/IM (Isopto, Atropair, Atropisol)

 

Antagonizes ACh at muscarinic receptor, leaving nicotinic receptors unaffected. In contrast to organophosphate insecticides, nerve agents rarely require >20 mg. Continue administration until excess muscarinic symptoms improve, which can be gauged by increased ease of breathing in the conscious patient or improvement in ease of ventilation in the intubated patient.

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Oximes

Class Summary

These reactivators of AChE enzyme are generally divided into 2 groups, monopyridinium and bispyridinium types. Pralidoxime belongs to the monopyridinium group and is the oxime used in the United States. Oximes should be administered concomitantly with atropine. After aging occurs, the usefulness of pralidoxime is minimal. VX has a slow aging process (estimated at 48 h); thus, delayed treatment with oximes may be beneficial. In contrast, aging half-life for GD is only 2-6 min, which makes pralidoxime impractical in this type of exposure.

A subset of the bispyridinium oximes termed H oximes (H for Hagedorn) contains variations of conventional extant oximes. These include agents such as HI-6, HGG-12, and HGG-42. They have been studied in the military setting but are not available for use in the United States. H oximes have shown promise in reactivating aged enzyme after GD exposure. The bispyridinium oxime termed obidoxime (Toxogonin) has been successfully tested for GB and GA intoxication. Pralidoxime is ineffective in GA.

In most cases, the specific agent involved is unknown. Do not delay or withhold antidote use while awaiting agent identification. The empiric use of pralidoxime is encouraged to prevent aging of the nerve agent with the AChE.

Pralidoxime (Protopam)

 

Oximes are reactivators of AChE. Can be used IM (as with military autoinjectors) or IV. The IV route is more likely to be practical in ED setting. The half-life of pralidoxime is 1 h, and it is renally excreted.

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Benzodiazepines

Class Summary

Seizures can be observed in severe nerve agent poisoning. For this reason, treatment with benzodiazepines has been advocated as part of the antidotal armamentarium. Experts advocate use of benzodiazepines prophylactically in patients with moderate-to-severe poisoning as well as with patients who are actively seizing. Dose should be 2-5 mg IV or 10 mg IM. With active seizures, diazepam should be titrated to effect.

Diazepam (Valium, Diazemuls, Diastat)

 

Belongs to benzodiazepine family, members of which act by stimulating GABA (the main inhibitory neurotransmitter in CNS) receptors, resulting in sedation and increased seizure threshold.

Midazolam (Versed)

 

Used as alternative in termination of refractory status epilepticus. Because midazolam is water soluble, it takes approximately 3 times longer than diazepam to reach peak EEG effects. Wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose.

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Contributor Information and Disclosures
Author

Larissa I Velez-Daubon, MD Professor, Program Director, Department of Surgery, Division of Emergency Medicine, University of Texas Southwestern Medical School, Parkland Memorial Hospital; Staff Toxicologist, Department of Surgery, Division of Emergency Medicine, North Texas Poison Center, Parkland Memorial Hospital

Larissa I Velez-Daubon, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Medical Toxicology, Society for Academic Emergency Medicine, American College of Emergency Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Daniel C Keyes, MD, MPH Associate Chair, Academic Affairs, Department of Emergency Medicine, St Joseph Mercy Hospital; Clinical Faculty, Emergency Medicine Residency, University of Michigan Medical School; Clinical Associate Professor, Department of Surgery, Division of Emergency Medicine and Toxicology, University of Texas Southwestern School of Medicine

Daniel C Keyes, MD, MPH is a member of the following medical societies: American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Fernando L Benitez, MD Assistant Medical Director, Dallas Metropolitan BioTel (EMS) System; Associate Professor in Emergency Medicine, Department of Surgery, Division of Emergency Medicine, University of Texas Southwestern Medical Center and Parkland Health and Hospital

Fernando L Benitez, MD is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Duane C Caneva, MD, MSc Senior Medical Advisor to Customs and Border Protection, Department of Homeland Security (DHS) Office of Health Affairs; Federal Co-Chair, Health, Medical, Responder Safety Subgroup, Interagency Board (IAB)

Disclosure: Nothing to disclose.

Additional Contributors

Fred Henretig, MD Director, Section of Clinical Toxicology, Professor, Medical Director, Delaware Valley Regional Poison Control Center, Departments of Emergency Medicine and Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital

Disclosure: Nothing to disclose.

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Table 1. Toxicity of Nerve Agents
AgentChemical NameLCt50, mgXmin/m3LD50,



mg



GAEthyl N -dimethylphosphoramidocyanidate4001000
GBIsopropyl methylphosphonofluoridate1001700
GDPinacolyl methylphosphonofluoridate50100
VXO-Ethyl S-2-diisopropylaminoethyl methylphosphonothioate1010
Table 2. Severity of Toxicity From Liquid and Vapor Exposures
Severity of ExposureSigns and Symptoms - Liquid*Signs and Symptoms - Vapor†
MinimalLocalized sweating at site



Localized fasciculations at site



Miosis



Rhinorrhea



Slight dyspnea



ModerateAbove-mentioned symptoms and the following:



Nausea, vomiting, and diarrhea



Generalized weakness



Above-mentioned symptoms and the following:



Moderate-to-marked dyspnea



(bronchorrhea and/or bronchoconstriction)



SevereAbove-mentioned symptoms and the following:



Loss of consciousness



Seizures



Generalized fasciculations



Flaccid paralysis and apnea



Above-mentioned symptoms and the following:



Loss of consciousness



Seizures



Generalized fasciculations



Flaccid paralysis and apnea



* Onset possibly delayed



† Rapid onset of symptoms



Table 3. Drugs Used to Treat Patients With Nerve Agent Poisoning*
DrugDose (Adult)RouteIndicationsContraindications
Atropine2 mg q5-10min prn



Note: The MARK 1 kit contains 2 mg of atropine.



IV/IM/ETTExcessive muscarinic symptomsRelative: IV route in hypoxia has been associated with ventricular fibrillation.
Pralidoxime chloride (Protopam, 2-PAM)15-25 mg/kg over 20 min; can be repeated after 1 h



Note: The MARK 1 kit contains 600 mg of pralidoxime.



IV/IMSymptomatic nerve agent poisoningRapid infusion may result in hypertension; may worsen symptoms in carbamate poisoning
Diazepam (Valium)2-5 mg IV



10 mg IM



IV/IMModerate or severe signs of poisoning, seizuresNone
*Adapted from Sidell, 1992.[3]
Table 4. Summary of Treatment Modalities According to Severity of Exposure*
Severity/Route of ExposureAtropine (Adult Dose)PralidoximeDiazepamOther
SuspectedNoNoNoDecontamination and 18-h observation for liquid exposures
Mild2 mg for severe



rhinorrhea or



dyspnea; may be



repeated



Administer if dyspnea



is not improving



or if GI



symptoms occur



NoDecontamination and 18-h observation for liquid exposures; oxygen
Moderate6 mg; may need to repeatAdminister with atropineAdminister even in absence of seizuresDecontamination; oxygen
SevereStart with 6 mg; may need to repeatAdminister with atropine; should repeat once or twiceAdminister even in absence of seizuresAirway, breathing, and circulation; decontamination
*Adapted from Sidell, 1992.[3]
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