History
The onset of symptoms after exposure to a V-series agent varies according to the route and quantity of exposure.
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After inhalation, onset is rapid due to the high vascularity of the lungs and because the lungs are primary target organs. However, it must be remembered that, due to the low volatility of the V agents, this is not the most common route of exposure.
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After cutaneous exposure, systemic symptoms may be delayed for minutes to hours; however, symptoms may present rapidly if a large exposure occurs. Clinical manifestations may be delayed for several hours or longer after lesser exposures, as the agent diffuses slowly through the keratin layers of the skin. This is in contrast to the G (volatile) agents, which are expected to cause onset of symptoms in the first few minutes after exposure.
The onset of symptoms also depends on the area of the skin that is exposed. In sites where the dermal layers are thin (eg, eyelids, ears), penetration by the nerve agent is more rapid.
In many situations, history of exposure to a nerve agent is absent. In case of a terrorist attack, suspect the diagnosis when multiple patients present with symptoms of cholinergic excess.
Occupational history may aid in making the diagnosis in cases of accidental releases. Chemical demilitarization laborers and laboratory workers may be at particular risk for exposure.
Physical
Clinical signs and symptoms are related to excessive stimulation at the nicotinic and muscarinic cholinergic receptors. Central effects may be mediated by cholinergic receptors, as well as by effects on N -methyl-D -aspartate-ergic and GABA-ergic systems. See Table 3 for a summary of the clinical effects of nerve agents.
Table 3. Pharmacologic Effects of Nerve Agents* (Open Table in a new window)
Receptor Involved |
Clinical Effect |
Acetylcholine, GABA, N -methyl-D -aspartate: Central (CNS) |
Anxiety, restlessness, seizures, failure to concentrate, depression, coma, apnea |
Acetylcholine: Muscarinic Postganglionic parasympathetic |
"DUMBELS" (commonly used mnemonic) D - Diarrhea U - Urination M - Miosis B - Bronchorrhea, bronchoconstriction E - Emesis L - Lacrimation S - Salivation Note: The other commonly used mnemonic "SLUDGE" is not used here, as it does not include an important sign and symptom: bronchorrhea and bronchoconstriction. |
Acetylcholine: Nicotinic Motor endplate Sympathetic and parasympathetic ganglia |
Pallor, tachycardia, hypertension, muscle weakness and/or paralysis, fasciculations Note: Some use the days of the week as an easy mnemonic for these: M - Mydriasis T - Tachycardia W - Weakness tH - Hypertension F - Fasciculations |
* Adapted from Marrs, Maynard, and Sidell. [10] |
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Eyes
The most common effects of nerve agents on the eyes are conjunctival injection and pupillary constriction, known as miosis. The patient complains of eye pain, dim vision, and blurred vision. This is most likely from direct contact between the agent and eye.
Miosis may persist for long periods and may be unilateral. Severe miosis results in the complaint of dim vision. Ciliary spasm also may cause eye pain.
Patients exposed to VX may not have miosis. This is most likely because the eye usually is not exposed directly to the agent, unlike with the G-series agents. Miosis may be a delayed sign of VX exposure.
Nose: Rhinorrhea is most common after a vapor exposure but also can be observed with exposures by other routes.
Lungs
Shortness of breath is an important complaint. Patients may describe chest tightness, respiratory distress, or gasping and even may present in apnea. Bronchoconstriction and excessive bronchial secretions cause these important life-threatening symptoms.
With severe exposures, death may result from central respiratory depression and/or complete paralysis of the muscles of respiration. Respiratory failure is the major cause of death in nerve agent poisoning.
Skeletal muscle
Fasciculations are the most specific identifiable manifestations of intoxication with these agents. Upon initial exposure, they can be localized, but they then spread to cause generalized involvement of the entire musculature (after severe exposures). Myoclonic jerks (twitches) may be observed. Eventually, muscles fatigue and a flaccid paralysis ensues.
Skin
With small liquid exposures, localized sweating can be observed along with the fasciculations. Generalized diaphoresis can occur with larger exposures.
Gastrointestinal
Abdominal cramping can be present. With larger exposures, nausea, vomiting, and diarrhea are more prominent.
Heart
The patient may present with either bradycardia or tachycardia. Heart rate depends on the predominance of sympathetic stimulation (resulting in tachycardia) or of the parasympathetic tone (causing bradycardia via vagal stimulation). Hypoxemia also increases adrenergic tone, which also manifests itself with tachycardia. Heart rate is thus 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 be observed. The 2 arrhythmias of greatest concern are torsade des pointes and ventricular fibrillation.
Central nervous system
Smaller exposures to nerve agents may result in behavioral changes such as anxiety, psychomotor depression, intellectual impairment, and unusual dreams.
Large exposures to nerve agents result in altered mentation, loss of consciousness, and seizures.
Degrees of toxicity
Most signs and symptoms are related to the excessive activation and subsequent fatigue at the cholinergic receptors. Some authors have divided exposures into minimal, moderate, and severe toxicity. Signs and symptoms associated with each exposure are summarized in Table 4.
Table 4. Severity of Toxicity from Liquid and Vapor Exposures (Open Table in a new window)
Severity of Exposure |
Signs and Symptoms - Liquid |
Signs and Symptoms - Vapor |
Onset of symptoms |
Possibly delayed toxicity |
Rapidly manifesting toxicity |
Minimal |
Localized sweating at site Localized fasciculations at site |
Miosis Rhinorrhea Mild dyspnea |
Moderate |
Fasciculations Diaphoresis Nausea, vomiting, and diarrhea Generalized weakness |
Above symptoms and the following: Moderate-to-marked dyspnea (bronchorrhea and/or bronchoconstriction) |
Severe |
Above symptoms and the following: Loss of consciousness Seizures Generalized fasciculations Flaccid paralysis and apnea |
Above symptoms and the following: Loss of consciousness Seizures Generalized fasciculations Flaccid paralysis and apnea |
Causes
The nerve agents are not readily available. Suspect nerve agent exposures in military or research laboratory workers who may have access to these substances. Also, suspect nerve agent poisoning when several patients present with signs and symptoms of cholinergic overstimulation. This presentation would be typical during a terrorist event, as seen in the 1995 Tokyo subway attack, in which sarin was released. Nerve agents have also been used as part of assasination attempts of high value targets, such as spies and government officials. [7, 8, 11]
Tables
Code Name |
Chemical Name |
VX |
O-Ethyl-S-[2(diisopropylamino)ethyl] methylphosphonothioate |
VE |
O-Ethyl-S-[2-(diethylamino)ethyl] ethylphosphonothioate |
VG |
O,O-Diethyl-S-[2-(diethylamino)ethyl] phosphorothioate |
VM |
O-Ethyl-S-[2-(diethylamino)ethyl] methylphosphonothioate |
V-gas |
Russian equivalent of VX |
Agent |
LCt50 (mg ⋅ min/m3) |
LD50 (mg) |
Aging Half-Life |
Tabun (GA) |
400 |
1000 |
46 h |
Sarin (GB) |
100 |
1700 |
5.2-12 h |
Soman (GD) |
50 |
100 |
40 sec to 10 min |
VX |
10 |
10 |
50-60 h |
Receptor Involved |
Clinical Effect |
Acetylcholine, GABA, N -methyl-D -aspartate: Central (CNS) |
Anxiety, restlessness, seizures, failure to concentrate, depression, coma, apnea |
Acetylcholine: Muscarinic Postganglionic parasympathetic |
"DUMBELS" (commonly used mnemonic) D - Diarrhea U - Urination M - Miosis B - Bronchorrhea, bronchoconstriction E - Emesis L - Lacrimation S - Salivation Note: The other commonly used mnemonic "SLUDGE" is not used here, as it does not include an important sign and symptom: bronchorrhea and bronchoconstriction. |
Acetylcholine: Nicotinic Motor endplate Sympathetic and parasympathetic ganglia |
Pallor, tachycardia, hypertension, muscle weakness and/or paralysis, fasciculations Note: Some use the days of the week as an easy mnemonic for these: M - Mydriasis T - Tachycardia W - Weakness tH - Hypertension F - Fasciculations |
* Adapted from Marrs, Maynard, and Sidell. [10] |
|
Severity of Exposure |
Signs and Symptoms - Liquid |
Signs and Symptoms - Vapor |
Onset of symptoms |
Possibly delayed toxicity |
Rapidly manifesting toxicity |
Minimal |
Localized sweating at site Localized fasciculations at site |
Miosis Rhinorrhea Mild dyspnea |
Moderate |
Fasciculations Diaphoresis Nausea, vomiting, and diarrhea Generalized weakness |
Above symptoms and the following: Moderate-to-marked dyspnea (bronchorrhea and/or bronchoconstriction) |
Severe |
Above symptoms and the following: Loss of consciousness Seizures Generalized fasciculations Flaccid paralysis and apnea |
Above symptoms and the following: Loss of consciousness Seizures Generalized fasciculations Flaccid paralysis and apnea |
Drug |
Dose |
Route |
Indications |
Contraindications |
Atropine |
2 mg q5-10min prn Note: the Mark 1 kit contains 2 mg of atropine |
IV/IM/ETT |
Excessive muscarinic symptoms |
Relative - IV route in hypoxia has been associated with ventricular fibrillation |
2-PAM Cl (pralidoxime chloride, Protopam) |
15-25 mg/kg over 20 min; can be repeated after 1 h Note: The Mark 1 kit contains 600 mg of pralidoxime. |
IV/IM |
Symptomatic nerve agent poisoning |
Rapid infusion may result in hypertension |
Diazepam (Valium) |
2-5 mg IV or 10 mg IM |
IV/IM |
Active seizures; administer as prophylaxis if moderate or severe signs of poisoning are present |
None |
*Adapted from Sidell. |
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Severity/Route of Exposure |
Atropine |
2-PAM Cl |
Diazepam |
Other |
Suspected |
No |
No |
No |
Decontamination and 18-h observation for liquid exposures |
Mild |
2 mg for severe rhinorrhea or dyspnea; may repeat prn |
Administer if patient has nonimproving dyspnea or GI symptoms |
No |
Decontamination and 18-h observation for liquid exposures; oxygen |
Moderate |
6 mg; may require repeat doses |
Administer with atropine |
Administer even in absence of seizures |
Decontamination, oxygen |
Severe |
Start with 6 mg; may need to repeat |
Administer with atropine; should repeat once or twice |
Administer even in absence of seizures |
ABCs, decontamination |
*Adapted from Sidell. |
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