Chemical Terrorism

By James A. Geiling, MD, FCCP

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Nerve Agents

Medical Management

Decontamination remains the mainstay of initial patient management in an attempt to mitigate agent effect and prevent contamination of other patients, equipment, and health-care workers. Patients require ventilatory support because of increased airway resistance (50 to 70 cm H₂O) and airway secretions. This support requirement may last for 30 min to 3 h in severe cases, even if treated.

Fortunately, atropine is an effective antidote for nerve agents. Atropine acts as a cholinergic blocking agent (ie, anticholinergic); its actions are most effective at muscarinic sites. If 2 mg of atropine is administered to an unexposed person, the results include mydriasis, decreased secretions and sweating, mild sedation, decreased GI motility, and tachycardia (a potential problem in unexposed persons who self-administer atropine based upon a perceived exposure). The recommended dosing in nerve agent treatment is 2 mg every 3 to 5 min titrated to secretions. In severe cases, 10 to 20 mg of atropine have been used in the first hour after exposure. Many of the eye symptoms can be relieved with topical homatropine or atropine.

Pralidoxime chloride (2-PAMCl) is another effective antidote for nerve agent casualties. 2-PAMCl is an oxime that attaches to the nerve agent and breaks the agent-enzyme bond. Its actions are most effective at nicotinic sites, thereby improving muscle strength; it does not decrease secretions. Unfortunately, aging decreases its effectiveness, ie, the longer the time interval between exposure to the agent and administration of 2-PAMCl, the less useful it becomes. For example, the aging period for Soman (GD) is 2 min, whereas that interval for sarin (GB) is 3 to 4 h. The dose is 15 to 25 mg/kg or approximately 1 g IV piggyback every 20 to 30 min.

Atropine and 2-PAMCl are often combined into an injector kit or system. The MARK I kit (Meridian Medical Technologies, Inc; Columbia, MD) used by the US military, which increasingly is becoming available on the civilian market, includes an AtroPen Auto-Injector (Meridian Medical Technologies, Inc) containing 2 mg of atropine and a ComboPen Auto-Injector (Meridian Medical Technologies, Inc) containing 600 mg of 2-PAMCl (8.9 mg/kg in a 70-kg person). In the US Army, each soldier normally is issued three kits. Military doctrine recommends that individuals exposed to nerve agent self-administer one MARK I kit if they are experiencing the effects of a nerve agent. If they remain symptomatic, they are instructed to seek "buddy aid" to determine if additional injections are necessary.

Diazepam remains the anticonvulsant drug of choice, based primarily on its history and demonstrated effectiveness. In the US military, diazepam is issued as a 10-mg autoinjector under guidance from the unit's commander and staff physician. Soldiers are trained to administer one autoinjector to their buddy after three MARK I kits have been used. Unit medical personnel carry additional diazepam.

There are several specific treatment caveats:

1. Titrate treatment to secretions, dyspnea, or retching and vomiting.
2. Miosis does not typically respond to atropine.
3. Treat eye pain/headache with topical atropine/homatropine.
4. Supportive care becomes the standard once the patient has been stabilized.
5. Fasciculations can persist after restoration of consciousness, ventilation, and even ambulation.

See Table 9 for a summary of recommendations.¹³

Pretreatment with pyridostigmine bromide was used in Operation Desert Storm and potentially could be used for high-threat civilian events. The dose is 30 mg q8h and will require public health or senior-level leadership decisions to implement. Pyridostigmine bromide binds to AChE through carbamylation and thereby blocks the nerve agent from attaching to AChE. This effectively increases the median lethal dose several-fold for soman (GD). Decarbamylation occurs after 4 h, whereupon the AChE becomes fully functional.

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