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

Nerve Agentsnerve agent toxicity on the human brain. Because ofrespiratory depression, it is possible to attribute muchof the reported CNS sequelae in human victims tohypoxic damage.A major challenge in interpreting the reports of longlastingneurobehavioral complaints in patients whohave survived nerve agent exposure is separating outthat part of the syndrome that is clearly psychological,including, in many cases, posttraumatic stress disorderssatisfying psychiatric criteria in The Diagnosticand Statistical Manual of Mental Disorders, 4th edition,from that which is due to direct toxicity of nerve agentupon the nervous system itself. Some of these reportsare summarized below.Only one case has been reported of peripheral nervedamage after human nerve agent intoxication. In thisone case, a victim of the Tokyo Aum Shinrikyo attackdeveloped distal sensory axonopathy months after hisexposure. Causality could not be established. 143Cardiovascular SystemLittle data exists on the cardiovascular effects ofnerve agents in humans. In mild-to-moderate intoxicationfrom nerve agents, blood pressure may be elevated,presumably because of cholinergic stimulationof ganglia or other factors, such as stress reaction.ArrhythmiasAfter nerve agent exposure, the heart rate maydecrease and the authors have observed that someatrial-ventricular (A-V) heart block (first-, second-, orthird-degree) with bradycardia may occur because ofthe stimulation of the A-V node by the vagus nerve. Insome cases an increase in heart rate may occur becauseof stress, fright, or some degree of hypoxia. Becausetreatment initiation is urgent in severely intoxicatedpatients, electrocardiograms (ECGs) have not beenperformed before atropine administration. However,if possible, an ECG should be done before drugs aregiven if the procedure will not delay therapy. In normalsubjects, atropine may cause a transient A-V dissociationbefore the onset of bradycardia (which precedestachycardia), and ChE-inhibiting substances may causebradycardia and A-V block. For reasons noted above,these transient rhythm abnormalities have not beenrecorded in patients with nerve agent intoxication.These rhythm disturbances are probably not clinicallyimportant.Reports of patients exposed to pesticides and theresults of animal studies provide additional informationabout cardiovascular reactions to nerve agents. Inone study, 144 dogs exposed to lethal amounts of sarinvapor had idioventricular rhythms within minutesafter exposure; following atropine therapy, some of thedogs had third- degree and first-degree heart blocksbefore a normal rhythm returned. In another study, 145conscious dogs had few cardiac rhythm changes aftersublethal doses (0.25–0.5 LD 50, administered subcutaneously)of VX. Four of five anesthetized dogsreceiving a 1-LD 50dose had arrhythmias, includingfirst-degree heart block and premature ventricularcomplexes; one had torsade de pointes (a type ofventricular tachycardia). Cardiac arrhythmias arenot uncommon in humans after organophosphorouspesticide poisoning. 146Dogs were instrumented to examine the cardiacchanges occurring for a month after IV administrationof 2 LD 50of soman. 147 Atropine and diazepam wereadministered shortly after soman exposure to controlseizure activity. During the study period, there wasincreased frequency of episodes of bradycardia withventricular escape, second-degree and third-degreeheart block, and independent ventricular activity(single premature beats, bigeminy, or runs of ventriculartachycardia).In a similar study, 148 rhesus monkeys were giventhe standard military regimen of pyridostigminebefore exposure to soman (1 LD 50, IM), and atropineand 2-PAM Cl after the agent. The monkeys weremonitored continuously for 4 weeks. Except for theperiod immediately after agent administration, theincidence of arrhythmias was the same as or less thanthat observed during a 2-week baseline period.Torsade de pointes has been reported after nerveagent poisoning in animals 145 and after organophosphoruspesticide poisoning in humans. 149 Torsade depointes is a ventricular arrhythmia, usually rapid, ofmultifocal origin, which on ECG resembles a patternmidway between ventricular tachycardia and fibrillation.It is generally preceded by a prolongation ofthe QT interval, it starts and stops suddenly, and itis refractory to commonly used therapy. It was firstdescribed as a clinical entity in the late 1960s; undoubtedlyit was seen but called by another name inexperimental studies with nerve agents before then.Recent studies have shown that sarin-exposed ratsdisplay pronounced QT segment prolongation forseveral weeks after near-lethal exposures, and thatthese animals showed an increased sensitivity toepinephrine-induced arrhythmias for at least 6 monthsafter exposure. 150In addition to the arrhythmias described above,studies have shown that animals (rats, nonhumanprimates) severely poisoned with nerve agents can developfrank cardiac lesions. 125,131,151–154 The early stage(15 minutes–several hours) of these lesions consists of179