eMedicine Specialties > Emergency Medicine > Warfare - Chemical, Biological, Radiological, Nuclear and Explosives

CBRNE - Nerve Agents, G-series - Tabun, Sarin, Soman

Kermit D Huebner, MD, FACEP, Research Director, Carl R Darnall Army Medical Center
Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Updated: Jul 8, 2008

Introduction

Background

The organophosphate nerve agents tabun (GA), sarin (GB), soman (GD), and cyclosarin (GF) are among the most toxic chemical warfare agents known. Together they comprise the G-series nerve agents, thus named because German scientists first synthesized them, beginning with GA in 1936. GB was discovered next in 1938, followed by GD in 1944 and finally the more obscure GF in 1949. The only other known nerve agent, O-ethyl S-(2-diisopropylaminoethyl) methylphosphonothioate (VX), is discussed in a separate article of this journal (see CBRNE - Nerve Agents, V-series - Ve, Vg, Vm, Vx).

G-series nerve agents share a number of common physical and chemical properties. At room temperature, the G-series nerve agents are volatile liquids, making them a serious risk for 2 types of exposure: dermal contact with liquid nerve agent or inhalation of nerve agent vapor. GB is the most volatile of these agents and evaporates at the same rate as water; GD is the next most volatile. Dispersal devices or an explosive blast also can aerosolize nerve agents. Nerve agent vapors are denser than air, making them particularly hazardous for persons in low areas or underground shelters. GB and GD are colorless, while GA ranges from colorless to brown. GB is odorless, while GA and GD smell fruity.

Because nerve agents are soluble in fat and water, they are absorbed readily through the eyes, respiratory tract, and skin. Vapor agents penetrate the eyes first, producing localized effects, then pass into the respiratory tract, with more generalized effects when the exposure is greater. Liquid agents penetrate the skin at the point of contact, producing localized effects followed by deeper penetration and generalized effects if the dose is large enough. Accordingly, the lethality of these agents varies with the route of exposure. For inhalational exposures to GB, the lethal concentration time product in 50% of the exposed population is 75-100 mg·min/m³. For dermal exposures, the lethal dose in 50% of the exposed population is 1700 mg.

Pathophysiology

Nerve agents act by first binding and then irreversibly inactivating acetylcholinesterase (AChE), producing a toxic accumulation of acetylcholine (ACh) at muscarinic, nicotinic, and CNS synapses. Excessive ACh at these cholinergic receptors may account for the spectrum of clinical effects observed in nerve agent exposure. At muscarinic receptors, nerve agents cause miosis, glandular hypersecretion (salivary, bronchial, lacrimal, bronchoconstriction, vomiting, diarrhea, urinary and fecal incontinence, bradycardia). At nicotinic receptors in skin, nerve agents cause sweating, and on skeletal muscle, they cause initial defasciculation followed by weakness and flaccid paralysis. At CNS cholinergic receptors, nerve agents produce irritability, giddiness, fatigue, lethargy, amnesia, ataxia, seizures, coma, and respiratory depression.

Nerve agents also cause tachycardia and hypertension via stimulation of the adrenal medulla. They also appear to bind nicotinic, cardiac muscarinic, and glutamate N -methyl-d-aspartate (NMDA) receptors directly, suggesting that they may have additional mechanisms of action yet to be defined. Nerve agents also antagonize gamma-aminobutyric acid (GABA) neurotransmission, which in part may mediate seizures and CNS neuropathology.

Clinical effects of nerve agents depend on the route and amount of exposure. The effect of inhalational exposure to nerve agent vapor in turn depends on the vapor concentration and the time of exposure. Exposure to low concentrations of nerve agent vapor produces immediate ocular symptoms, rhinorrhea, and in some patients, dyspnea. These ocular effects are secondary to the localized absorption of GB vapor across the outermost layers of the eye, causing lacrimal gland stimulation (tearing), pupillary sphincter contraction (miosis), and ciliary body spasm (ocular pain). As the exposure increases, dyspnea and gastrointestinal symptoms ensue.

Exposure to high concentrations of nerve agent vapor causes immediate loss of consciousness, followed shortly by convulsions, flaccid paralysis, and respiratory failure. These generalized effects are caused by the rapid absorption of nerve agent vapor across the respiratory tract, producing maximal inhibition of AChE within seconds to minutes of exposure. Nerve agent vapor is expected to have had its full effect by the time victims present to the emergency care system.

The effect of dermal exposure to liquid nerve agent depends on the anatomic site exposed, ambient temperature, and dose of nerve agent. Percutaneous absorption of nerve agent typically results in localized sweating caused by direct nicotinic effect on the skin, followed by muscular fasciculations and weakness as the agent penetrates deeper and a nicotinic effect is exerted on underlying muscle. In moderate dermal exposures, vomiting and/or diarrhea occur. Vomiting and/or diarrhea soon after exposure are ominous signs. With further absorption, full-blown systemic or remote effects occur.

Because percutaneous absorption takes time, the onset of symptoms in dermal exposures usually is delayed. Even with thorough decontamination, symptoms may not occur until several hours have elapsed if some agent was absorbed prior to decontamination. A small droplet of GB liquid on the skin may not produce any clinical effects for as long as 18 hours postexposure. A large droplet of GB liquid rapidly causes loss of consciousness, seizures, paralysis, and apnea but only after a brief asymptomatic period typically lasting 10-30 minutes.

Miosis cannot be used as a marker for the severity of nerve agent exposure, because it depends on the route and time course of exposure. In inhalational exposures, miosis occurs early and frequently. In such exposures, normal pupil size is predictive of nontoxicity. However, in dermal exposures at sites distinct from the eye, miosis occurs later in the progression of toxicity and depends on whether significant systemic absorption has occurred.

Nerve agents cause death via respiratory failure, which in turn is caused by increased airway resistance (bronchorrhea, bronchoconstriction), respiratory muscle paralysis, and most importantly, loss of central respiratory drive.

Two chemical properties of nerve agents also provide the rationale for effective measures against them. First, nerve agents are hydrolyzed readily by alkaline solutions, which explains why soap and water or hypochlorite solutions are effective skin decontaminants. Second, the bond between the nerve agent and AChE takes time to chemically mature and become a stable covalent bond. During the period immediately after nerve agent binding to enzyme, the bond is vulnerable to disruption by agents called oximes. This aging phenomenon forms the pharmacologic basis for the effective use of the antidote, pralidoxime, during this early window of opportunity before the bond becomes permanent.

Frequency

United States

Nerve agent exposure is extremely rare in the US.

International

Despite international attempts to control the proliferation of chemical weapons, nerve agents reportedly still are stockpiled by the militaries of several countries.

To date, no large-scale military deployment of a nerve agent has occurred during war, although indirect evidence exists that the Iraqi military used GB against Kurdish villagers in 1988 as well as during the Iraq-Iran War.

In 1994, the Japanese terrorist cult, Aum Shinrikyo, synthesized and then deployed GB against civilians at Matsumoto, Japan, killing 8 people. The following year, the same terrorist group released GB again in the infamous Tokyo Subway sarin attack, killing 13 and sending 5500 persons to local hospitals.

Clinical

History

Symptoms of nerve agent toxicity vary with the type of cholinergic receptor affected, muscarinic, nicotinic, or CNS.

• Respiratory - Dyspnea, cough, chest tightness, wheezing
• Neurologic - Headache, weakness, fasciculations, extremity numbness, decreased level of consciousness (LOC), vertigo, dizziness, convulsions
• Ophthalmic - Eye pain, blurred vision, dim vision, conjunctival injection, tearing
• Ear, nose, throat - Rhinorrhea
• Gastrointestinal - Nausea, vomiting, diarrhea, tenesmus, fecal incontinence
• Genitourinary - Urinary incontinence
• Dermal - Sweating
• Psychological - Agitation
• General - Fatigue

Physical

Signs of nerve agent toxicity also vary with the type of cholinergic receptor affected.

• Respiratory - Tachypnea, wheezing, respiratory failure
• Cardiovascular - Bradycardia, tachycardia
• Neurologic - Decreased LOC, weakness, fasciculations, seizure
• Ophthalmic - Miosis, tearing, conjunctival injection
• Dermal - Sweating

Causes

Nerve agent exposure may occur as a result of an industrial accident involving nerve agent production, accidental release from a military stockpile, chemical warfare, and chemical terrorism.

Differential Diagnoses

CBRNE - Nerve Agents, Binary: GB2, VX2
CBRNE - Nerve Agents, V-series: Ve, Vg, Vm, Vx
Toxicity, Organophosphate and Carbamate

Workup

Laboratory Studies

• While no laboratory test exists to directly measure nerve agent levels in serum or urine, the acute effects of nerve agents can be estimated by measuring the percent reduction in the activity of erythrocytic (RBC) cholinesterase.
  • RBC cholinesterase and plasma cholinesterase (pseudocholinesterase) appear to have a physiologic role as buffers for the tissue AChEs found in the nervous system. These 2 enzymes are clinically important, because their activities can be assayed directly in blood, whereas the tissue cholinesterases cannot. Activity of RBC cholinesterase is considered a more sensitive indicator of nerve agent toxicity than that of plasma cholinesterase.
  • Despite the clinical use of RBC cholinesterase, keep certain limitations in mind when using the activity of RBC cholinesterase to interpret nerve agent effects.
    • Activity of RBC cholinesterase is subject to some individual variation.
    • Without establishing the baseline value of RBC cholinesterase in individuals, measuring the percent reduction in enzyme activity is difficult.
    • Poor correlation exists between clinical effects of nerve agents and the percent reduction of RBC cholinesterase activity at low-dose exposures. Accordingly, RBC cholinesterase activity always must be correlated with the patient's clinical status and never should determine patient disposition alone.
  • A good guideline is that severe clinical effects tend to correlate with a 20-25% reduction in RBC cholinesterase activity.
  • A rising RBC cholinesterase level indicates that no further nerve agent absorption is occurring and that the enzyme is regenerating. RBC cholinesterase is replaced fully every 120 days at the natural regeneration rate of RBCs (approximately 1%/d).
  • Draw blood for RBC cholinesterase activity level prior to administering oxime antidotes.
• Respiratory impairment in nerve agent intoxication produces expected derangement in arterial blood gas values, including a reduction in PaO₂.
• Hypokalemia has been reported in GB intoxication, although the mechanism is unclear.

Imaging Studies

• Chest x-ray may be helpful in treating patients with significant pulmonary symptoms.

Other Tests

• A number of electrocardiographic changes have been reported in nerve agent intoxication, including bradycardia and varying degrees of atrioventricular block (first through third degree) from the direct muscarinic effect on the heart and tachycardia and ventricular dysrhythmias from hypoxia. Nerve agent toxicity has been associated with PR interval prolongation, QT prolongation, and torsade de pointes.
• Bedside EEG monitoring is recommended for patients paralyzed from nerve agent exposure, because paralysis from nicotinic effects of these agents may mask seizures from CNS effects.

Treatment

Prehospital Care

• Personal protective equipment
  • A key consideration in prehospital care is protection of emergency medical service personnel from exposure to the nerve agent until victims are decontaminated thoroughly or the need for decontamination is excluded.
  • Personnel should wear personal protective equipment including protective suits, heavy butyl rubber gloves, and air-supplied respirators (eg, self-contained breathing apparatus) when entering a scene posing a nerve agent vapor risk or when treating victims exposed to liquid nerve agents.
• Decontamination
  • Goals of decontamination are to prevent further absorption of nerve agents by victims and to prevent the spread of nerve agents to others. If possible, decontamination should take place at the site of exposure.
  • Decontamination of liquid nerve agent exposure consists of removing all clothing, copiously irrigating with water to physically remove the nerve agent, and then washing the skin with an alkaline solution of soap and water or 0.5% hypochlorite solution (made by diluting household bleach 1:10) to chemically neutralize the nerve agent. Avoid hot water, strong detergents, and vigorous scrubbing, since they tend to enhance nerve agent absorption.
  • Exposure to nerve agent vapor does not require decontamination.
• Airway, breathing, and circulation
  • Patients with signs and symptoms of moderate nerve agent toxicity require supplemental oxygen, pulse oximetry, cardiac monitoring, and intravenous (IV) access.
  • Early endotracheal intubation and ventilatory support are critical in patients with manifestations of severe toxicity (eg, unconsciousness, seizures, paralysis, apnea), since respiratory failure is the principle cause of death in nerve agent exposure.
• Medications
  • Prehospital medical personnel may have access to nerve agent treatment autoinjectors.
  • Use of nerve agent treatment autoinjectors by prehospital personnel should be guided by local policy.

Emergency Department Care

• Personal protective equipment: Emergency department (ED) personnel should wear personal protective equipment similar to that worn by prehospital care personnel until adequate decontamination of victims is assured or the need for decontamination is eliminated.
• Decontamination
  • Goals of decontamination are to prevent further absorption of nerve agent by victims and to prevent the introduction of nerve agent into the clean ED environment.
  • Liquid nerve agent exposure requires formal decontamination as outlined in Prehospital Care before victims enter the ED.
  • No decontamination is necessary in vapor exposure.
  • Previously reported terrorist episodes have demonstrated that victims who physically can flee the scene frequently bypass emergency medical services (EMS) and go directly to the nearest ED.
• Airway, breathing, and circulation
  • The rapidity with which nerve agents act necessitates rapid medical response.
  • Moderately symptomatic patients require supplemental oxygen, pulse oximetry, cardiac monitoring, and early IV access.
  • Early endotracheal intubation and ventilatory support is paramount in treating patients with manifestations of severe toxicity.
  • Suction is an important adjunct to airway management, since airway secretions may be profuse in these patients.
  • Rapid sequence intubation may be required for airway treatment of patients with respiratory failure caused by nerve agent exposure. If rapid sequence intubation is used, avoid succinylcholine, since it is metabolized by plasma cholinesterase, leading to markedly prolonged paralysis.
  • Because atropine administered to hypoxic patients is associated with an increased risk of ventricular fibrillation, administer it after initial oxygenation and ventilation if possible.

Consultations

Consultation with a toxicologist via a regional poison control center may be helpful.

Medication

Reversal of nerve agent toxicity depends on the prompt parenteral administration of the 2 antidotes, atropine and pralidoxime.

Although IV administration of these antidotes is preferred, this may not be practical in combat situations or civilian mass casualty incidents. The US military Mark 1 kit contains 2 IM autoinjectors, one with atropine 2 mg and the other with pralidoxime 600 mg, to be administered simultaneously in the event of nerve gas exposure. The recommended number of Mark 1 kits to be administered varies from 1-3 and depends on the route of exposure, severity of clinical effects, and elapsed time after exposure.

Deployed US military personnel typically carry 3 Mark 1 kits per person. The Antidote Treatment-Nerve Agent Auto-Injector (ATNAA) contains 2.1 mg of atropine and 600 mg of pralidoxime chloride in a single injector. A pediatric dosage atropine autoinjector (AtroPen) is commercially available. This product contains atropine and does not include pralidoxime. A Pediatric Expert Advisory Panel recommends the use of the Mark 1 kit in children 3 years and older.

While seizures complicating nerve agent exposure often respond to IV atropine and pralidoxime, they also may require IV benzodiazepines titrated to effect. The convulsant antidote for nerve agent (CANA) autoinjector consists of diazepam and is recommended after 3 Mark 1 kits have been administered. Midazolam has been considered as a replacement to diazepam. Midazolam is twice as potent and acts more rapidly than diazepam in nonhuman primates with nerve agent–induced seizures.

Another common complication of vapor nerve agent exposure is ocular pain, which may be treated effectively with a mild, mydriatic-cycloplegic ophthalmic solution (eg, 0.5% tropicamide). Atropine or homatropine ophthalmic solution also can be used to treat ocular pain, but these agents tend to exacerbate visual impairment.

Pretreatment with pyridostigmine before exposure to GA, GD, and GF may improve survival. No evidence supports the chemoprophylactic use of pyridostigmine against GB or VX.

A number of other novel treatments currently are under investigation. Newer H-series oximes and dioximes (HI-6, HLo7) have greater ability to reactivate phosphorylated AChE. These agents demonstrate greater efficacy against all nerve agents (particularly GD) in animal studies and have direct antimuscarinic and antinicotinic actions to antagonize the effects of nerve agents. Other promising treatments currently under investigation include exogenous cholinesterase and the use of human monoclonal antibodies against nerve agents, both of which scavenge nerve agents and prevent them from binding to tissue AChE.

Anticholinergics

Act directly on smooth muscles and secretory glands innervated by cholinergic nerves to block muscarinic effects of excess ACh.

Atropine (Isopto, Atropair, Atropisol)

Initial DOC for symptomatic victims of nerve agent exposure; acts via muscarinic receptors to reverse bronchoconstriction, bronchorrhea, abdominal pain, nausea, vomiting, and bradycardia; appears to be involved in stopping seizure activity. Because atropine does not act on nicotinic receptors, has no effect on muscle weakness or paralysis. The most important therapeutic endpoints are drying of respiratory secretions, reversal of bronchoconstriction, and reversal of bradycardia; pupillary response and tachycardia are not useful measures of adequate atropinization; >20 mg rarely is needed in first 24 h, unlike in organophosphate insecticide poisoning where up to 200 mg may be required; atropine almost never is required beyond 24 h postexposure.

Dosing

Adult

2 mg IV q2-5min, titrated to effect; although IV is preferred, also may be administered IM/ETT in similar doses

Pediatric

0.02 mg/kg IV q2-5min, titrated to effect; 0.1 mg minimum dose

Interactions

Coadministration with other anticholinergics or TCAs may have an additive anticholinergic effect

Contraindications

Documented hypersensitivity

Precautions

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

Caution in patients with coronary artery disease, dysrhythmias, congestive heart failure, hypertension, peritonitis, ulcerative colitis, hiatal hernia with reflux esophagitis, prostatic hypertrophy, and Down syndrome
In setting of true nerve agent toxicity, benefits of antidotal atropine are expected to outweigh any risks

Oximes

Reactivate AChEs, which have been inactivated from phosphorylation by nerve agents (or other compounds, such as organophosphate pesticides).

Pralidoxime chloride (2-PAM Cl, Protopam)

Reverses skeletal muscle weakness by reactivating AChE; acts by disrupting covalent bond between nerve agent and AChE before it becomes permanent. Bonds between different nerve agents and AChE have various aging periods. The half-time of the aging reaction for GD is approximately 2 min, for GB it is 5 h, and for GA it is 13 h. Accordingly, administer pralidoxime IV as early as possible (ideally concurrently with atropine). Excreted rapidly and almost completely unchanged by the kidneys.
Administration over 30-40 min minimizes adverse effects (eg, hypertension, headache, blurred vision, epigastric pain, nausea, vomiting).

Dosing

Adult

1-2 g IV; although absorption is slower, also may administer IM

Pediatric

15-25 mg/kg IV

Interactions

Use barbiturates with caution because action of barbiturates is potentiated by AChE inhibitors; antagonism with neostigmine, pyridostigmine, and edrophonium; morphine, theophylline, aminophylline, succinylcholine, reserpine, and phenothiazines can worsen condition of patients poisoned by organophosphate insecticides or nerve agents (do not administer)

Contraindications

Documented hypersensitivity

Precautions

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

Rapid injection can cause tachycardia, laryngospasm, muscle rigidity, pain at injection site, blurred vision, diplopia, impaired accommodation, dizziness, drowsiness, nausea, tachycardia, hypertension, and hyperventilation; can precipitate myasthenia crisis in patients with myasthenia gravis and muscle rigidity in normal volunteers; decrease in renal function increases drug levels in blood because 2-PAM is excreted in urine; can produce transient elevation in creatine phosphokinase; 1 of 6 patients has an elevation in SGOT and/or SGPT

Benzodiazepines

Believed to exert antiseizure effect by enhancing binding of the major CNS inhibitory neurotransmitter, GABA, to A-type GABA receptors in the CNS, reducing depolarization of neurons and preventing generation and spread of seizures.

Diazepam (Valium, Diazemuls, Diastat)

Indicated for treatment of seizures associated with nerve agent toxicity. Depresses all levels of CNS function by increasing activity of the inhibitory neurotransmitter GABA.

Dosing

Adult

5-10 mg IV q10-20min, titrated to effect; may repeat in 2-4 h prn; not to exceed 30 mg/8 h

Pediatric

0.05-0.3 mg IV over 2-3 min q15-30min, titrated to effect; may repeat in 2-4 h prn; not to exceed 10 mg

Interactions

Coadministration with alcohol, barbiturates, phenothiazines, and MAOIs increases CNS toxicity and respiratory depression

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Use diazepam with caution in setting of nerve agent toxicity or CNS depressants, since may lead to further respiratory depression; caution in hepatic failure or hypoalbuminemia, since may result in toxic diazepam levels

Mydriatic-cycloplegics

Dilate iris and relax ciliary muscle, reversing ocular pain and miosis of nerve agent toxicity.

Tropicamide (Mydriacyl, Tropicacyl)

Anticholinergic compound that reverses miosis and relieves ocular pain in nerve agent toxicity. Acts by blocking cholinergic stimulation of sphincter muscle of iris and ciliary muscle. When applied as weaker preparation (0.5%), causes pupillary dilation (mydriasis); when applied as stronger preparation (1%), results in loss of accommodation (cycloplegia). Acts rapidly; effect is relatively short lasting.

Dosing

Adult

1-2 gtt of 0.5% solution to eye; may repeat in 5 min; patients with heavily pigmented irides may require larger doses

Pediatric

Not established

Interactions

None reported

Contraindications

Documented hypersensitivity; in patients with primary glaucoma or patients with narrow anterior chamber angles

Precautions

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

Caution in older patients, since increased intraocular pressure is more likely to be encountered in this age group; estimate depth of angle of anterior chamber before administration; advise patients not to engage in hazardous activity (ie, driving) while pupils are dilated; anticholinergic effects may cause CNS disturbances in infants and children; compression of lacrimal sac with a finger for 2-3 min after administration decreases systemic absorption

Cholinesterase inhibitors

Temporarily bind and inhibit AChE, thus blocking subsequent binding of certain nerve agents to AChE. Although usually used to treat myasthenia gravis or reverse nondepolarizing neuromuscular blockade, also may be useful as chemoprophylactic agents when administered before exposure to certain nerve agents.

Pyridostigmine (Mestinon, Regonol)

Orally available cholinesterase inhibitor, which may be useful as chemoprophylactic agent when administered prior to exposure to GA, GD, and GF. This recommendation is based on animal studies; little information is available regarding the efficacy of pyridostigmine chemoprophylaxis in humans. Only effective in preventing peripheral (non-CNS) effects of nerve agents; since it exists in an ionized form (quaternary amine), does not readily pass into CNS and thus cannot prevent nerve agent–induced CNS injury; no evidence demonstrates that pretreatment before exposure to GB or VX is effective.

Dosing

Adult

30 mg PO q8h prior to nerve agent exposure for 3 wk total

Pediatric

Not established

Interactions

Increases effects of depolarizing neuromuscular blockers; increases toxicity of edrophonium

Contraindications

Documented hypersensitivity; bronchial asthma; mechanical intestinal obstructions; mechanical urinary obstructions

Precautions

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

Inhibits breakdown of ACh; resulting cholinergic excess may lead to muscarinic and nicotinic adverse effects in dose-dependent manner, similar to spectrum of toxicity observed with nerve agents; muscarinic adverse effects include nausea, vomiting, diarrhea, abdominal cramping, hypersalivation, bronchorrhea, and miosis; approximately 50% of military personnel taking prophylactic pyridostigmine during the Gulf War at the dose listed above experienced flatus, loose stools, and abdominal cramping; 5-30% experienced urinary frequency and urgency; <5% suffered headaches, rhinorrhea, diaphoresis, and paresthesias; muscarinic adverse effects are reversible with atropine; potential nicotinic adverse effects include diaphoresis, muscle cramps, fasciculations, and weakness; effects of cholinergic excess can be controlled to some extent by careful selection of dose; bromide component may cause skin rash; long-term effects of pyridostigmine administration to healthy individuals is unclear

Follow-up

Further Inpatient Care

• Severely poisoned patients in respiratory arrest may need ventilatory assistance for several hours despite aggressive antidotal therapy. Patients in critical condition caused by complications of nerve agent poisoning, such as hypoxic brain injury, may require prolonged intensive care.

Further Outpatient Care

• Toxic effects of GB usually peak within minutes to hours and resolve within 24 hours.
  • Patients who inhale nerve agent vapor suffer peak toxic effects before arriving in the ED.
  • Patients who present to the ED with only ocular findings following vapor exposure can be discharged home safely. Refer patients discharged home with miosis or other eye complaints to an ophthalmologist.
• Onset of signs and symptoms in patients with dermal exposure to liquid GB may be delayed for as long as 18 hours.
  • Observe these patients in the ED or hospital for at least 18 hours.
  • As discussed in Lab Studies, RBC or plasma cholinesterase activity alone never should determine disposition and always must be correlated with the patient's clinical status.
• A variety of neurobehavioral symptoms may persist in patients exposed to nerve agents. Such patients may benefit from neurologic consultation.

Transfer

• Transfer patients only after performing appropriate decontamination and appropriately addressing the need for an airway and ventilation.

Complications

• Little data are available describing long-term effects of nerve agent exposure.
• Structural brain damage in animals has been attributed to nerve agent–induced seizures. A consensus panel of experts concluded that structural brain damage does not occur until seizures have lasted longer than 45 minutes.
• Miosis-related visual problems in dim light and mental lapses have been reported as long as 6-8 months after nerve agent exposure.
• Some information about long-term sequelae has emerged from studies of victims of the Tokyo Subway GB attack. Postural imbalance has been reported 8 months after exposure to GB. Fatigue, asthenia, nausea, shoulder stiffness, and blurred vision have been reported 3 years after exposure to GB.

Prognosis

• Patients who survive nerve agent exposure have a good prognosis.

Patient Education

• Counsel patients who are discharged home with miosis to avoid driving at night.
• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center. Also, see eMedicine's patient education articles Chemical Warfare and Personal Protective Equipment.
• For more information, see Medscape's Disaster Preparedness and Aftermath Resource Center.

Miscellaneous

Medicolegal Pitfalls

• A number of pitfalls may occur in the assessment and treatment of patients with exposure to nerve agents.
• The most serious mistake is failure to recognize signs and symptoms of cholinergic excess as being caused by nerve agent toxicity. This may lead to further contamination of emergency care personnel and life-threatening delays in emergency medical care of the primary victims.
• Once nerve agent poisoning is diagnosed, another pitfall lies in using the ocular finding of miosis to interpret the severity of exposure or to guide atropine therapy (except when exposure is clearly via vapor and miosis is absent). Similarly, overreliance on the reduction in RBC cholinesterase activity levels can lead to false impressions about the severity of exposure.
• Another pitfall in assessment may occur when emergency care personnel fail to suspect occult seizures in paralyzed patients. Since prolonged seizures lead to structural brain injury, these patients require bedside EEG monitoring.
• Major mistakes also may occur in treatment. The most devastating error is for first responders to fail to adequately protect themselves from nerve agent exposure before entering the scene, turning these individuals into victims. EMS personnel always must follow the edict of first ensuring that the scene is safe.
• Failure to adequately decontaminate victims of liquid nerve agent exposure at the scene can lead to contamination of both prehospital and hospital personnel and equipment.
• When emergency care personnel fail to recognize the rapidity with which nerve agents act, critical interventions (eg, airway management) may be delayed.
• Another potential error occurs when emergency care providers fail to appreciate the time course of liquid nerve agent exposure. They may fail to recognize that in low-dose exposure to liquid nerve agent, signs and symptoms of cholinergic excess may not appear for up to 18 hours. Conversely, in high-dose liquid nerve agent exposure, a brief asymptomatic period after exposure of 10-30 minutes may occur before the patient acutely deteriorates.
• Administration of the antidote atropine before hypoxemia is treated may cause ventricular fibrillation. Administration of succinylcholine as part of a rapid sequence intubation protocol may lead to markedly prolonged paralysis. Always administer the antidote pralidoxime as early as possible, since it is ineffective after the aging period has elapsed.

Multimedia

Media file 1: 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.

PDF available at http://img.medscape.com/pi/emed/ckb/emergency_medicine/756148-829124-831648-831745.pdf.

References

1. Dunn MA, Hackley BE, Sidell FR. Pretreatment for nerve agent exposure. In: Medical Aspects of Chemical and Biological Warfare. 1987:181-196.

2. Holstege CP, Kirk M, Sidell FR. Chemical warfare. Nerve agent poisoning. Crit Care Clin. Oct 1997;13(4):923-42. [Medline].

3. Kato T, Hamanaka T. Ocular signs and symptoms caused by exposure to sarin gas. Am J Ophthalmol. Feb 1996;121(2):209-10. [Medline].

4. McDonough JH. Midazolam: An Improved Anticonvulsant Treatment for Nerve Agent Induced Seizures. Defense Technical Information Center. JAN 2002;[Full Text].

5. Nakajima T, Sato S, Morita H, Yanagisawa N. Sarin poisoning of a rescue team in the Matsumoto sarin incident in Japan. Occup Environ Med. Oct 1997;54(10):697-701. [Medline].

6. Nakajima T, Ohta S, Fukushima Y, Yanagisawa N. Sequelae of sarin toxicity at one and three years after exposure in Matsumoto, Japan. J Epidemiol. Nov 1999;9(5):337-43. [Medline].

7. National Center for Disaster Preparedness. Atropine Use in Children After Nerve Gas Exposure. Pediatric Expert Advisory Panel (PEAP) Info Brief. Spring 2004;1:[Full Text].

8. Nozaki H, Hori S, Shinozawa Y, et al. Relationship between pupil size and acetylcholinesterase activity in patients exposed to sarin vapor. Intensive Care Med. Sep 1997;23(9):1005-7. [Medline].

9. Okumura T, Takasu N, Ishimatsu S, et al. Report on 640 victims of the Tokyo subway sarin attack. Ann Emerg Med. Aug 1996;28(2):129-35. [Medline].

10. Rickett DL, Glenn JF, Beers ET. Central respiratory effects versus neuromuscular actions of nerve agents. Neurotoxicology. Spring 1986;7(1):225-36. [Medline].

11. Sidell FR, Borak J. Chemical warfare agents: II. Nerve agents. Ann Emerg Med. Jul 1992;21(7):865-71. [Medline].

12. Sidell FR. Nerve agents. In: Medical Aspects of Chemical and Biological Warfare. 1987:129-179.

13. Tokuda Y, Kikuchi M, Takahashi O. Prehospital management of sarin nerve gas terrorism in urban settings: 10 years of progress after the Tokyo subway sarin attack. Resuscitation. Feb 2006;68(2):193-202. [Medline].

14. Yokoyama K, Araki S, Murata K, et al. A preliminary study on delayed vestibulo-cerebellar effects of Tokyo Subway Sarin Poisoning in relation to gender difference: frequency analysis of postural sway. J Occup Environ Med. Jan 1998;40(1):17-21. [Medline].

Keywords

nerve agents, G-series nerve agents, tabun, sarin, soman, GA, GB, GD, GF, organophosphate nerve agents, terrorist attack, terrorism, chemical weapons, chemical warfare agents, toxic warfare agents, nerve agent exposure, nerve agent toxicity

Contributor Information and Disclosures

Author

Kermit D Huebner, MD, FACEP, Research Director, Carl R Darnall Army Medical Center
Kermit D Huebner, MD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, Association of Military Surgeons of the US, Society for Academic Emergency Medicine, and Society of USAF Flight Surgeons
Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey L Arnold, MD, FACEP, Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center
Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine and American College of Physicians
Disclosure: Nothing to disclose.

Medical Editor

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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Rick Kulkarni, MD, 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.

© 1994- by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)