CHEMICAL WARFARE: Nerve Agent Poisoning
Section snippets
HISTORY
The discovery of nerve agents occurred when German scientists were attempting to develop superior pesticides. In the late 1930s, a German scientist, Dr. Gerhard Schrader, was performing research into effective pesticides based upon organophosphorus bonding. While testing tabun, a drop was spilled in the laboratory.12 Within minutes the research staff developed symptoms of anticholinesterase poisoning. Subsequent experiments with animals showed that vapor exposure resulted in their rapid demise.
CHEMICAL PROPERTIES
Tabun, soman, sarin, and VX are the four major nerve agents known to have been manufactured. These four agents are organophosphates and have a structure similar to the more familiar organophosphate pesticides, such as malathion. Lethal concentration-time (LCt)50s are shown in Table 1. This means, for example, that 50% of an unprotected group would die following 1 minute inhalation of air that contained 10 mg of VX per cubic meter. For comparison, the highly toxic compound hydrogen cyanide has
MECHANISM OF ACTION
Acetylcholine (ACh) is a neurotransmitter found throughout the central nervous system, the sympathetic and parasympathetic autonomic ganglia, the postganglionic parasympathetic nervous system, most sympathetic sweat glands, and at the skeletal muscle motor end plate (Fig. 1).8, 79 ACh binds to and activates muscarinic and nicotinic receptors. Activating muscarinic receptors stimulates or inhibits cellular function, through G proteins, at visceral smooth muscle, cardiac muscle, and secretory
CLINICAL PRESENTATION
The onset, severity, and signs and symptoms of nerve agent poisoning vary widely, as listed below:
Muscarinic Manifestations
Ophthalmic: conjunctival injection, lacrimation, miosis, dim or blurred vision, diminished visual acuity, loss of dark adaptation, ocular pain exacerbated by accommodation
Respiratory: perfuse watery rhinorrhea, stridor, wheezing, cough, increased bronchial secretions, chest tightness, dyspnea, apnea, cyanosis
Cardiovascular: bradydysrhythmias, prolongation of
LABORATORY
Laboratory studies are useful, but have limitations. The clinical laboratory cannot measure serum or urine concentrations of nerve agents or their metabolites. Instead, the nervous system's AChE activity is approximated by measuring plasma and erythrocytic cholinesterase activity. Plasma or “pseudocholinesterase” is made in the liver and is rapidly inactivated by nerve agents. Its activity is also depressed by liver disease, pregnancy, infection, and oral contraceptives.
Erythrocytic (RBC) or
Considerations for Emergency Response to Mass Exposure and for Self-protection
An event involving nerve agents may create confusion; panic; multiple seriously ill or dead victims; and a major emergency medical system, police, and military response. Large numbers of casualties would overwhelm any community's emergency services. Chaos would be an appropriate description of the scene and local hospitals. In the early phases of an emergency response, the toxin's identification may be unknown. The risk of secondary contamination is not just of concern to the emergency
SUMMARY
The threat of civilian and military casualties from nerve agent exposure has become a greater concern over the past decade. After rapidly assessing that a nerve agent attack has occurred, emphasis must be placed on decontamination and protection of both rescuers and medical personnel from exposure. The medical system can become rapidly overwhelmed and strong emotional reactions can confuse the clinical picture. Initially, care should first be focused on supportive care, with emphasis toward
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Address reprint requests to Christopher P. Holstege, MD, Indiana Poison Center, Methodist Hospital, I-65 at 21st Street, P.O. Box 1367, Indianapolis, IN 46206–1367