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

Medical Aspects of Chemical Warfareinduce neutralizing monoclonal antibody.PTX toxicity has been studied in several animalspecies, each showing similar sensitivities 43,44 and clinicaleffects to humans. In general, most experimentalanimals show clinical signs of drowsiness, weakness,vomiting, respiratory distress, diarrhea, convulsions,shock, hypothermia, and death within 30 to 60 minutesof IV injection. Early signs of PTX poisoning in dogsinclude defecation and vomiting. 30 Rats and nonhumanprimates have demonstrated similar sensitivity to IVPTX challenge with 24-hour LD 50of 89 ng/kg and 78ng/kg, respectively. 43 Following IV administration ofPTX, nonhuman primates become drowsy, weak, andataxic. Vomiting sometimes occurs (incidence not reported),43 followed by collapse and death.PTX causes a moderate skin reaction in rabbits 45 aswell as an increase in histidine decarboxylase activityin mice after topical PTX application to the skin. 46Based on histamine release data in rat mast cells, PTXmay have immunological effects. 47 It causes a depolarizationof the membranes of myelinated fibers, spinalcord, and squid axons; induced norepinephrine releasefrom adrenergic neurons 48 and clonal rat pheochromocytomacells 49 ; and causes a temperature-dependentpotassium loss from rat erythrocytes, followed byhemolysis in a matter of hours. 50PTX also leads to dysrhythmias and vasospasm inanimals. It exerts cytotoxic effects in rat aortic smoothmuscle, leading to surface granularities, vacuoles,rounding, and cell death; increased release of lactatedehydrogenase; increased ionic conductance to sodiumand potassium; and profound membrane depolarizationon electrophysiological recording. 14 Finally, PTXhas a direct cardiotoxicity in vivo, resulting in atrioventricularblock, extrasystoles, ventricular tachycardia,coronary vasoconstriction, and ventricular fibrillation.The shape and rhythm of the EKG is abnormal, showingS-T segment elevation most likely due to coronaryvasoconstriction. 35 Death from PTX appears to be secondaryto coronary artery vasoconstriction, reducingblood flow to cardiac tissues, resulting in necrosis. Thisleads to cardiac failure and progressive myocardialischemia, ventricular fibrillation, and cardiac arrestobserved by EKG in nonhuman primates followingIV exposure to PTX. 43Food poisoning incidents by accidental PTX ingestionare not uncommon in Japan, 26,36 and clinical signsand symptoms have been reported after cases of humanPTX ingestion. 26,27,34,36 The patients in a Taniyamaet al case report suffered severe muscle pains, dyspnea,apnea, and discharge of black urine. 27 Symptom onsetoccurred 3 to 36 hours following ingestion. On laboratoryfindings, serum CPK levels were above the normalrange and were reported to be 700–23,800 IU/L. All ofthe patients observed in the study recovered. Reportedmuscle pains abated, CPK levels returned to normal,and urine color resolved, although recovery took approximately1 month (Exhibit 19-1).In cases of accidental poisoning it is difficult toascertain how much PTX the victim ingested. Toxindistribution and concentration, the precise quantityof food consumed, and the amount of toxin ingestedcannot be adequately determined, as PTX toxicity byingestion has not been thoroughly studied. An Okanocase report involved a 55-year-old male who consumedthe raw meat and liver of a blue humphead parrotfishcontaminated with PTX. The patient developedprogressive weakness and myalgia in his extremities5 hours after ingesting the toxin. Rhabdomyolysisand myocardial damage developed with serum CPKlevels elevated to 40,000 IU/L by the third day followingingestion. Serum aldolase, serum myoglobin, andurinary myoglobin were similarly elevated. Elevatedmyosin light chain levels and alterations in the EKGwere noted. 26 After mannitol-alkaline diuresis oncedaily for a period of 4 days, the patient recovered.Weakness and myalgias subsided within 4 weeks.PTX is less toxic by ingestion than by other routesof exposure. 51 Its stability and the potency differencesfrom various routes of entry must be further studiedto estimate the threat of PTX.Treatment. Life support may be required to minimizerespiratory and cardiovascular compromiseafter PTX intoxication. Treatment of PTX-intoxicatedvictims consists of rapid diagnosis, decontaminationwith copious amounts of water, and general supportivecare. Any patient suspected of ingesting PTXshould be monitored in a controlled setting until allsigns and symptoms of toxicity have abated. In casesof oral exposure, syrup of ipecac is not recommendeddue to the rapid nature of PTX absorption. Activatedcharcoal should be given emergently in aqueous slurryfor suspected ingestion only in patients who are awakeand able to protect their airways. In patients at risk forseizures or mental status changes, activated charcoalshould be administered by personnel capable of airwaymanagement to prevent aspiration in the event ofspontaneous emesis. Activated charcoal is only usefulif administered within approximately 30 minutes ofingestion. Cathartics are not recommended due to thevomiting, diarrhea, and electrolyte imbalance causedby PTX.Oxygenation, hemoglobin, hematocrit, plasma freehemoglobin, urinalysis, and other indices of hemolysisshould be monitored. Transfusion of blood or packedred blood cells may be necessary to treat hemolysis.Early treatment should be aimed at controlling acutemetabolic disturbances (hyperkalemia, hyponatremia,620