CBRNE - Nerve Agents, Binary - GB2, VX2 Clinical Presentation

  • Author: Larissa I Velez-Daubon, MD; Chief Editor: Robert G Darling, MD, FACEP   more...
 
Updated: Mar 16, 2010
 

History

The onset of symptoms after an exposure to a nerve agent varies depending on the route of exposure and the nature of the specific agent.

  • After inhalation, onset is extremely rapid because of the high vascularity of the lungs. The lungs are also important primary target organs. Dim or blurry vision caused by diffusion of the nerve agent through the cornea and subsequent interaction with the pupillary muscle is extremely common after a vapor exposure.
  • After dermal exposure to the G (volatile) agents, systemic effects may be delayed for minutes. In the case of VX, systemic effects may not appear until several hours after dermal exposure. The symptoms tend to be localized at first, with sweating and fasciculations, and may thus be overlooked by the patient. The onset of symptoms also depends on the area of skin that is exposed, and on the presence of sweat and ambient temperature. The rate of penetration is greatest in the thinner areas of the skin.
  • In many patients, history of exposure to a nerve agent is absent. In case of a terrorist attack, suspect the diagnosis when several patients present with symptoms of cholinergic excess. Occupational history may also aid in making the diagnosis. Military personnel and laboratory personnel are at a higher risk for exposures to the nerve agents.
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Physical

Clinical signs and symptoms are related to excessive stimulation at the cholinergic nicotinic and muscarinic receptors both centrally and peripherally. Some central (CNS) effects may not be mediated by cholinergic receptors. In particular, some effects are suspected to occur on glutamate N -methyl-d-aspartate (NMDA) and gamma-butyric acid (GABA) receptors, which may contribute to nerve agent–mediated seizures and CNS neuropathology. See below for a summary of the clinical effects of nerve agents (adapted from Marrs, 1996).[1]

Signs and symptoms correlate with the severity of the exposure and are primarily related to excessive activation and subsequent fatigue at the cholinergic receptors. Some authors have divided exposures into minimal, moderate, and severe. Signs and symptoms associated with each level of exposure are summarized in Table 2.

Table 2. Severity of Toxicity From Liquid and Vapor Exposures (Open Table in a new window)

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



Central (CNS) effects

CNS effects include the following:

  • Anxiety
  • Restlessness
  • Seizures
  • Failure to concentrate
  • Depression

Acetylcholine muscarinic (postganglionic parasympathetic)

DUMBELS is a commonly used mnemonic, as follows:

  • D - Diarrhea
  • U - Urination
  • M - Miosis
  • B - Bronchorrhea, bronchoconstriction
  • E - Emesis
  • L - Lacrimation
  • S - Salivation

Acetylcholine nicotinic (motor endplate, sympathetic and parasympathetic ganglia)

These signs and symptoms include the following:

  • Pallor
  • Tachycardia
  • Hypertension
  • Muscle weakness or paralysis
  • Fasciculations

Eyes

Some of the most common effects of nerve agents are miosis and conjunctival injection. Patients may report eye pain, dim vision, and blurred vision. This most likely is due to direct contact between the agent and the pupillary muscle of the eye.

Miosis may persist for long periods and may be unilateral. Dim vision is, in part, due to the severe miosis, whereas the eye pain is directly caused by ciliary muscle spasm.

Patients exposed to VX may not experience miosis. This is probably because exposures to VX are generally dermal, and, thus, the eye is not directly exposed to the agent. However, miosis may be present as a delayed sign of VX exposure.

Nose

Rhinorrhea is common after vapor exposure, from direct exposure of the nasal mucosa to the nerve agent.

Rhinorrhea can also result as part of the systemic toxicity seen after exposures by other routes.

Lungs

Shortness of breath is another common symptom after any form of exposure. It can vary from a sensation of tightness in the chest to frank respiratory distress, pulmonary edema, gasping, and apnea. This shortness of breath is caused by both the bronchoconstriction and excessive bronchial secretions that may result from muscarinic overactivity.

In severe exposures, paralysis of the respiratory muscles occurs due to respiratory muscle fatigue.

Muscarinic and nicotinic hyperactivity in the central nervous system can also produce a centrally mediated apnea.

Respiratory failure due to central apnea, bronchorrhea and bronchoconstriction, respiratory muscle paralysis, or a combination thereof is often the cause of death in nerve agent poisoning.

Skeletal muscle

Fasciculations, either localized or generalized, are observed after severe exposures. Myoclonic jerks (twitches) may also be observed.

Eventually, the muscles fatigue and a flaccid paralysis ensues.

Skin

With small liquid exposures, localized sweating and fasciculations can occur.

Generalized, profuse diaphoresis can occur with larger exposures.

Gastrointestinal

Abdominal cramping can occur.

With larger exposures, nausea, vomiting, and diarrhea are more prominent.

Heart

The patient may present with either bradycardia or tachycardia. Increases in heart rate results from predominance of the adrenergic stimulation, whereas predominant parasympathetic tone results in vagal stimulation and bradycardia. Heart rate is an unreliable sign of nerve agent poisoning.

Many disturbances in cardiac rhythm have been reported after both organophosphate and nerve agent poisonings.

Heart blocks and premature ventricular contractions can occur.

The most concerning arrhythmias reported are torsade des pointes and ventricular fibrillation.

Central nervous system

Smaller exposures to nerve agents have reportedly resulted in behavioral changes such as anxiety, psychomotor depression, intellectual impairment, and unusual dreams.

Large exposures to nerve agents result in loss of consciousness, central apnea, and seizures.

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Causes

Nerve agents are not readily available. Suspect nerve agent exposures in military personnel or research laboratory workers who may have access to these substances. Also suspect nerve agent poisoning when several patients present with signs of cholinergic overstimulation. This second presentation would be typical during a terrorist attack.

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Contributor Information and Disclosures
Author

Larissa I Velez-Daubon, MD  Associate Professor, Associate Program Director, Department of Surgery, Division of Emergency Medicine, University of Texas Southwestern Medical School, Parkland Memorial Hospital; Associate Program Director and 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 Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

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, and National Association of EMS Physicians

Disclosure: Nothing to disclose.

Daniel C Keyes, MD, MPH  Vice Chair, Academic Affairs, Department of Emergency Medicine, John Peter Smith Health Network; 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, and American College of Physicians-American Society of Internal Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

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.

Francisco Talavera, PharmD, PhD  Senior Pharmacy Editor, eMedicine

Disclosure: eMedicine Salary Employment

Rick Kulkarni, MD 

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

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  Adjunct 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, American Telemedicine Association, and Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

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Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html.
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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