Effects Following Acute High-Dose Sarin

Short-Term Effects

It is well established that high doses of sarin can have severe effects that are termed the acute cholinergic syndrome. The effects of acute poisonings from sarin have been seen in studies of servicemen who volunteered for studies of the health effects of low-dose exposure to sarin and other chemical-warfare (CW) agents (NRC, 1985; Baker and Sedgwick, 1996), a study of workers accidentally exposed to sarin (Duffy et al., 1979; Burchfiel and Duffy, 1982), and studies after terrorist attacks in Matsumoto and Tokyo, Japan (Murata et al., 1997; Nakajima et al., 1998, 1999; Yokoyama et al., 1998a,b,c).

The following conclusion was reached in the present report after a review of the literature on sarin:

There is sufficient evidence of a causal relationship between exposure to sarin and a dose-dependent acute cholinergic syndrome that is evident seconds to hours subsequent to sarin exposure and resolves in days to months.

The acute cholinergic syndrome has been recognized for decades and has been documented in human studies summarized in Chapter 3. As discussed in Chapter 2, animal and mechanistic data are consistent with the effects seen in humans. The syndrome, as well as cholinergic signs and symptoms, is evident seconds to hours after exposure and usually resolves in days to months. The syndrome and the cholinergic signs and symptoms are produced by sarin’s irreversible inhibition of the enzyme acetylcholinesterase. Inactivation of the enzyme that normally breaks down the neurotransmitter acetylcholine leads to the accumulation of acetylcholine at cholinergic synapses. Excess quantities of acetylcholine result in widespread overstimulation of muscles and nerves. At high doses, convulsions and death can occur.

Long-Term Effects

Many health effects are reported in the literature to persist after sarin exposure: fatigue, headache, visual disturbances (asthenopia, blurred vision, and narrowing of the visual field), asthenia, shoulder stiffness, and symptoms of posttraumatic stress disorder (PTSD). Sarin exposure has been followed by abnormal test results, of unknown clinical significance, on the digit symbol test of psychomotor performance, electroencephalographic (EEG) records of sleep, event-related potential, visual evoked potential, and computerized posturography.

Studies of servicemen who volunteered for a study of the health effects of low-dose exposure to sarin and other CW agents did not demonstrate any long-term health effects of exposure to cholinesterase inhibitors (NRC, 1985; Page,



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