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

Medical Aspects of Chemical Warfarecurrently used in experimental trials. In some instances100% oxygen supportive therapy in conjunction withsodium thiosulfate and sodium nitrite may be synergisticallybeneficial. Treatment with sodium bicarbonatecan be used to reverse lactate acidosis. Ballantyne andSalem 75 provide an in-depth review of HCN exposureeffects, mechanisms of action, antidotes, and sources ofexposure, and Chapter 11, Cyanide Poisoning, providesadditional information.PerfluoroisobutyleneA significant exposure hazard from fires and chemicalindustrial accidents, PFIB causes severe pulmonaryedema in the peripheral airway compartment. In micePFIB exposure caused a significant reduction in protectivesulfhydryl concentrations and myeloperoxidaseactivity, as well as enhancement of the influx of polymorphonuclearleukocytes into the lung. 76 Exposurecan disrupt the air–blood barrier, cause hemorrhagicpulmonary edema, and increase BALF protein leak.Treatment with cholinolytic 3-quinuclidinyl benzilate30 minutes before or 10 hours after exposure resultedin reduced indices of acute lung injury as measured bylung wet weight to body weight ratio, reduced bloodviscosity and reduced mortality.PhosgeneBecause of phosgene’s extensive industrial use andextreme toxicity, a great deal of experimental modeldevelopment, mechanistic toxicology, and therapeutictesting has taken place over the past 25 years. Phosgeneis very chemically reactive, especially with importantcellular components of biomolecules, such as sulfhydryl,amine, and hydroxyl groups. 25 This chemicalreactivity occurs primarily in the distal lung peripheralairway compartment, and exposure has been foundto directly affect type I pneumocytes, 77,78 increase lavagepolymorphonuclear phagocytes, 79 decrease bothcytochrome-c-oxidase and adenosine triphosphataseactivity, 80 and significantly reduce lung adenosinetriphosphate concentrations. 81 Some limited and questionableevidence suggests that phosgene inhalationmay be involved in toxic encephalopathy in humans 82 ;however, this study involved long-term exposure tomany chemical solvents in an industrial environment,which may have confounded the role of phosgene asa single causative agent of neurotoxicity.Recent experimental work with phosgene in animalshas shown that bronchoconstriction, enhancedpulmonary edema formation, elevated leukotriene production,increased lipid peroxidation byproducts, anddecreases in both dynamic compliance and lung tissuecAMP are several of the major responses of the lungto phosgene inhalation. 59,83,84 Phosgene has been foundto be toxic through normal metabolic detoxificationmechanisms unrelated to direct inhalation exposure.In hepatocytes, phosgene binds with phospholipidssuch as phosphatidylcholine and ethanolamine underhypoxic or normoxic conditions. 85–87 These bonds couldbe mechanistically important during the injury processbecause alveolar surfactant is largely phospholipid incontent and alveolar edema causes a locally hypoxicenvironment. Experimental evidence has shown thatphosgene exposure has a significant effect on lungsurfactant levels. 88Based on these detrimental effects, postexposuretherapeutic efforts have succeeded in reducing lunginjury in exposed animals. Studies involving rodentsand rabbits have shown that the effects of increasedpulmonary edema, airway pressure, and pulmonaryartery pressure, as well as the inhibition of the releaseof reactive metabolites (such as the permeabilityenhancingleukotrienes, vasoactive prostaglandins,and free radicals) can all be reduced following treatmentafter exposure. Compounds approved by the USFood and Drug Administration such as isoproterenol,ibuprofen, aminophylline, and N-acetylcysteine canprotect the lung from further damage. 33,83,89,90 In somecases, treatment can enhance survival rates. 89 No datasupports the use of steroids to treat human exposure.However, medical management guidelines from theCenters for Disease Control and Prevention recommendstarting intravenous corticosteroids in cases ofsevere exposure even if the patient is asymptomatic.Steroids administrated intravenously seem to be morebeneficial when administered before exposure, 59 althoughthis finding has yet to be tested clinically ona large scale. Not all effective treatment against phosgene-inducedlung injury involves the use of drugs.In large swine exposed to phosgene, effective therapyinvolved the modification of ventilation parametersafter exposure. Lower tidal volume, decreased ventilationrates, and decreased positive end-expiratorypressure, in addition to intravenous saline and glucosesupport, reduced cardiovascular effects, lung damage(reduced edema formation), and the histopathologicalresponse of the lung tissue. 40In addition to producing acute lung injury to thecentral and peripheral compartments, phosgene, chlorine,riot control agents, smokes, and ammonia canhave long-term effects. Fibrosis, bronchiolitis obliterans,chronic obstructive pulmonary disease, RADS, pulmonaryfunction abnormalities, alveolitis, and bronchiectasisare some of the sequela of exposure. The exposurecould have been a one-time event, chronic exposureover years, or a multiple chemical exposure. In addition,gases such as PFIB, phosgene, and chlorine may give riseto ARDS in the days to weeks after exposure, especially354