Military chemical weapons of the nerve agent type are currently considered a significant terrorist threat to civilian populations worldwide in the aftermath of the Tokyo sarin attack in 1995 by a religious extremist cult and, of course, the incidents of September 11, 2001, and the subsequent intentional mail-borne anthrax outbreak in the United States in October 2001. The Iraqi chemical weapons attacks on the Kurdish population of northern Iraq in the late 1980s are believed to have involved numerous pediatric victims. Children may be victims of terrorism as well, as was witnessed in the 1995 Oklahoma City bombing. The potential use of such potent poisons as terrorist weapons has resulted in the search for management strategies that would allow for the rapid treatment of mass casualties resulting from exposure to these agents (1,2).

Nerve agents are organophosphorus compounds that act as potent inhibitors of acetylcholinesterase, similarly to organophosphate pesticides (3,4,5). After exposure, the inhibition of these agents becomes irreversible after a variable period of time, a process termed “aging.” Four compounds are currently recognized as military nerve agents: tabun, sarin, soman, and VX (“Venom X”). With soman, aging occurs within minutes, while with the others, it takes several hours. This is relevant because, in a mass casualty scenario, rapidly treating large numbers of critical patients in the field or soon after arrival at a hospital may result in many lives saved and considerably less long-term morbidity if treatment can be provided prior to the onset of the aging phenomenon.

Nerve agent–induced anticholinesterase inhibition results in the accumulation of acetylcholine at neural junctions, resulting initially in stimulation of cholinergic transmission. However, the impact on the neuromuscular junction of somatic nerves is relatively unique, with initial stimulation followed shortly by paralysis. In addition to the neuromuscular junction, cholinergic synapses are found in the central nervous system (CNS); several autonomic sites, including both sympathetic and parasympathetic nerve endings; and sympathetic and parasympathetic ganglia. The resulting cholinergic syndrome is classically divided into central, nicotinic (neuromuscular junction and sympathetic ganglia), and muscarinic (smooth muscle and exocrine gland) effects.

The clinical presentation for a given patient will depend on the dose and route of exposure (3,4). Children may be more susceptible due to heavier exposure (living “closer to the ground”; all nerve agents are heavier than air), higher minute ventilation, and possibly greater susceptibility to CNS manifestations (1,6,7,8).

With low-dose vapor exposures, toxic manifestations include eye findings, particularly dimmed vision and miosis, as well as rhinorrhea, mild dyspnea, and wheezing. As the dose increases, more severe respiratory effects, nausea, vomiting, and muscle weakness are expected. Exposure to very high vapor concentrations results in rapid onset of paralysis and seizures; death due to respiratory arrest may occur within minutes.

Diagnosis of nerve agent toxicity is primarily achieved by clinical recognition and response to antidotal therapy. The overall
treatment approach for these agents should focus on airway and ventilatory support, aggressive use of antidotes, prompt control of seizures with a benzodiazepine (or even empiric benzodiazepine therapy in severe cases before seizures have occurred), and decontamination as necessary (see also Chapter 128). Atropine, in relatively large doses, is used for its antimuscarinic effects, and pralidoxime chloride (2-PAM) serves to reactivate of acetylcholinesterase if aging has not yet occurred. Atropine counteracts bronchospasm and excess bronchial secretions, bradycardia, the gastrointestinal effects of nausea, vomiting, diarrhea, and cramps and may lessen seizure activity. However, atropine does not improve skeletal muscle paralysis. 2-PAM dissociates organophosphate from the cholinesterase, and its effects are observed predominantly at the neuromuscular junction, with improved muscle strength. The recommended initial dose of atropine is 0.05 mg/kg (minimum dose 0.1 mg, maximum 5 mg) administered intravenously or intramuscularly for moderate to severe toxicity, which can be repeated every 2 to 5 minutes as needed until bronchospasm and excess respiratory secretions are relieved. 2-PAM in doses of 25 mg/kg administered intravenously or intramuscularly (maximum dose 1 g intravenously, 2 g intramuscularly) is recommended promptly in all serious cases, along with concomitant atropine treatment. This can be repeated in 30 to 60 minutes for severe cases and then again every hour for 1 to 2 additional doses in cases with persistent weakness or high atropine requirement.

In individual cases of severe organophosphate poisoning, atropine and 2-PAM are optimally administered intravenously. However, animal data suggest that intravenous atropine may provoke arrhythmias in hypoxic animals, and so hypoxia should be corrected, if possible; otherwise intramuscular use is preferable initially (4). In all cases, the intramuscular route is acceptable if intravenous access is not readily available, which might be of considerable relevance in a pediatric mass casualty incident.

Most U.S. emergency medical services teams now stock intramuscular autoinjectors of atropine and 2-PAM. These are spring-loaded injector devices that can be easily used by both medical and nonmedical personnel. Many clinicians are familiar with this technology, which is used in an epinephrine autoinjector, or “EpiPen.” Such autoinjectors inject medications more forcefully than traditional syringe and needle intramuscular injections, with an enhanced rate of absorption (2-PAM) and onset of clinical effects (atropine) observed (9,10,11,12). Currently, there is little clinical experience to draw from regarding the efficacy of autoinjector therapy for mass casualty exposures to a nerve agent, let alone specific pediatric experience. However, in dire circumstances, these autoinjectors would seem to offer an optimal route of rapid antidote administration in children. An atropine autoinjector (AtroPen) has recently been approved by the U.S. Food and Drug Administration (FDA) for pediatric use in just this context and is manufactured in 0.25-, 0.5-, and 1-mg doses in addition to the adult-sized dose of 2 mg (Table 121.1). The AtroPen delivers one dose only in a total volume of up to 0.7 mL and is nonrefillable. It employs a 22-gauge needle that delivers the atropine in a circular field of distribution with a 0.2- to 0.78-inch depth of insertion. The adult-intended 2-PAM autoinjector contains 600 mg in a 2-mL volume.