Medical Aspects of Chemical Warfare (2008) - The Black Vault

Nerve Agentsof jerks and tremor.Central Nervous System and BehaviorBehavioral and psychological changes in humansexposed to ChE-inhibiting substances have been discussedin numerous reports. The incidence of psychologicaleffects is higher in individuals who have hadmore severe exposures to nerve agents, but they mayoccur, probably more frequently than is commonlyrecognized, in individuals who have received a smallexposure and have no or minimal physical signs orsymptoms. Although the effects may begin as late as1 day after exposure, they usually start within a fewhours and last from several days to several weeks.In the Aum Shinrikyo attacks of 1995, some patientscomplained of effects lasting longer, even months. 78Whether these are direct nerve agent effects, posttraumaticstress disorder, or a combination is not known.Common complaints include feelings of uneasiness,tension, and fatigue. Exposed individuals may beforgetful, and observers may note that they are irritable,do not answer simple questions as quickly andprecisely as usual, and generally display impairedjudgment, poor comprehension, decreased ability tocommunicate, or occasional mild confusion. Grossmental aberrations, such as complete disorientation orhallucinations, are not part of the symptom complex.Several of the findings on behavioral and psychologicalchanges that occur following exposure to nerve agentsor pesticides have recently been summarized. 79,80Studies of Behavioral and Psychological ChangesIn one of the earliest studies of the effects of ChEinhibitingsubstances, 38 behavioral and psychologicalchanges were reported in 49 of 60 subjects (of whom50 were normal and 10 had myasthenia gravis) afterdaily IM doses (1.5–3.0 mg) of DFP. Changes werereported about 1 hour after dose administration. Themost prominent CNS effects reported were excessivedreaming (33 subjects); insomnia (29 subjects); andjitteriness, restlessness, increased tension, emotionallability, and tremulousness (29 subjects). The authorsof the study noted, without comment, that one subjectreported visual hallucinations. Hallucinations are notmentioned elsewhere as an effect of ChE inhibitors.Later, similar effects were reported as sequelae of accidentalexposure to nerve agent poisoning. 81,82One report 66 suggests that several workers accidentallyexposed to sarin had some behavioral effects.Another report 72 lists “weakness” (actually tiredness),nervousness, and drowsiness as complaints from 16 of40 workers accidentally exposed to small amounts ofnerve agent vapor.In a series 58 of 49 workers who were accidentallyexposed to sarin or tabun (a total of 53 exposures), 13workers reported sleep disturbances, 12 reported moodchanges, and 10 reported easy fatigability. Overall, 51%had CNS effects. The report authors pointed out thatthe complex of CNS symptoms may not fully developuntil 24 hours after exposure. The data on blood ChEactivities (both RBC-ChE and BuChE) in these workerswere scanty. The individual with the greatest ChEinhibition, however, had an RBC-ChE activity of 33%of his personal control value, which suggests that theexposures were not severe. No correlation betweenthe presence or severity of symptoms and the degreeof ChE inhibition was seen, and most of the effects ofexposure disappeared within 3 days. Systemic atropinewas not given to any of these individuals, which suggeststhat therapy is unnecessary if a paucity of physicalsigns exists. The report authors concluded that mildintoxication by nerve agents may cause psychologicaldisturbances and that these disturbances might haveserious consequences to the individuals and to thosedependent on their judgment. 58In a series 83 of 72 workers exposed to sarin, two reporteddifficulty in concentration, five reported mentalconfusion, five reported giddiness, and four reportedinsomnia. All but two of these individuals were consideredto have been exposed to a small amount of sarin;they were given 2 mg of atropine intramuscularly, and12 others received atropine orally (0.4–0.8 mg). RBC-ChE ranged from less than 9% to more than 100% ofthe individual ’ s control activity.Behavioral changes and whole-blood ChE activitieswere reported in another study 84 in which VX wasplaced on the skin of volunteers. Since VX preferentiallyinhibits RBC-ChE and has relatively little effecton BuChE, the decreases in whole-blood ChE activitieswere assumed to indicate mainly inhibition of RBC-ChE. In subjects with whole-blood ChE activities of10% to 40% of control (RBC-ChE activities < 20% ofcontrol), 30% reported anxiety, 57% had psychomotordepression, 57% had intellectual impairment, and 38%had unusual dreams. Of those with whole-blood ChEactivities of 41% to 80% of control (RBC-ChE activitiesof 20%–40% of control), 8% reported anxiety, 4% hadpsychomotor depression, 4% had intellectual depression,and 33% had unusual dreams. Nausea and vomitingwere the other symptoms noted. Some subjects hadboth psychological and gastrointestinal effects, withonsets often separated by several hours. Some subjectshad symptoms related to only one organ system.Overall, the onset of signs and symptoms occurred3.5 to 18 hours after percutaneous exposure, and maximaldepression in blood ChE occurred 3 to 8 hours after175