Medical Aspects of Chemical Warfare (2008) - The Black Vault
Medical Aspects of Chemical Warfare (2008) - The Black Vault Medical Aspects of Chemical Warfare (2008) - The Black Vault
Vesicantstion without significant tissue injury will be able toreturn to duty. Determining the level of injury requiresobservation for 3 to 7 days. Anyone with documentedmustard lung injury producing bronchial pneumoniaor pseudomembrane formation will be unable to returnto duty for several months. Those with severe casesmay never return to duty.Skin. Only patients with small TBSA injuries (lessthan 5%) in noncritical areas will be able to return toduty following treatment with topical antibiotic, dressings,and oral analgesics. Burns to the hands, feet, face,axillae, and groin are all potentially disabling. (A recentaccident victim required hospitalization in a burn centerfor burns on the arm and leg amounting to 6% to 7%TBSA, sustaining serious disability from a relativelysmall surface area injury.) For all but the mildest ofinjuries return to duty will require weeks to months.Burns by liquid on the skin and in the eye cause themost severe injury. It is possible, however, to receive anearly total body burn with mustard vapor with effectsno more severe than those from a second-degree sunburn.Such a mild vapor burn would take 48 or morehours to develop. However, a vapor burn developingin only a few hours could be as severe as a liquid burn.Severity of a mustard burn is dependent upon the totalabsorbed dose of vapor and liquid.Long-Term EffectsMustard burns may leave areas of hypopigmentationor hyperpigmentation, sometimes with scarring.Individuals who survive an acute, single mustardexposure with few or no systemic or infectious complicationsappear to recover fully. Previous cardiopulmonarydisorders, severe or inadequately treatedbronchitis or pneumonitis, a prior history of smoking,and advanced age all appear to contribute to long-termchronic bronchitis; there is no definitive way to determinewhether these conditions are the result of aging,smoking, or a previous mustard exposure. Casualtieswith severe airway lesions may later have postrecoveryscarring and stenosis, which predispose the individualto bronchiectasis and recurrent pneumonia. 59An important late sequela of mustard inhalation is atracheal/bronchial stenosis that necessitates bronchoscopyand possible dilatation, isotonic saline lavages,laser surgery, or silicone stents. 235 Mustard has been reportedto create a long-term sensitivity to smoke, dust,and similar airborne particles, probably as a result ofclinically inapparent bronchospasm. 59,240The relationship between mustard exposure andsubsequent cancer has been the subject of much study.It seems clear that individuals who were exposed tomustard daily for long periods (eg, workers in mustardproduction plants) have a slightly higher incidence ofcancer of the airways, primarily the upper airways. 241–243According to two separate reports, the associationof one or two exposures on the battlefield with subsequentcancer is not clear; in a third report, the relationbetween mustard exposure and subsequent cancer isequivocal. 244–246 Watson and associates reviewed themustard exposure–cancer incidence relation in 1989,concluding that the maximum estimates of lifetimecancer risks with sulfur mustard are not great, butneither are they entirely negligible. 247In 1991 the National Academy of Sciences appointeda committee to survey the health effects of mustardand lewisite. 246 Veterans of World War II who had beenexposed to mustard and lewisite as subjects in testprograms were presenting at Veterans Administrationhospitals with complaints of illnesses they believed tobe associated with the exposures. The committee wasrequested to survey the literature to assess the strengthof association between these chemical agents andthe development of specific diseases. The committeereported finding a causal relationship between exposureand various cancers and chronic diseases of therespiratory system; cancer and certain other problemsof the skin; certain chronic eye conditions; psychologicaldisorders; and sexual dysfunction. They foundinsufficient evidence for a causal relationship betweenexposure and gastrointestinal diseases, hematologicaldiseases, neurological diseases, and cardiovasculardiseases (except those resulting from infection followingexposure). Some of these conclusions were notwell supported. For example, there were no cases ofskin cancer reported, and the alleged psychologicaldisorders were from the trauma of exposure, not fromthe agent (see Chapter 9, Long-Term Health Effects ofChemical Threat Agents).LEWISITELewisite (b-chlorovinyldichloroarsine), an arsenicalvesicant, is of secondary importance in the vesicantgroup of agents. It was synthesized in the early 20thcentury and has seen little or no battlefield use. 248Lewisite is similar to mustard in that it damages theskin, eyes, and airways; however, it differs from mustardbecause its clinical effects appear within secondsof exposure. An antidote, British antilewisite (BAL[dimercaprol]), can ameliorate the effects of lewisite ifused soon after exposure. For use as a chemical warfareagent, lewisite has some advantages over mustard butalso some disadvantages.291
Medical Aspects of Chemical WarfareMilitary UseA research team headed by US Army CaptainWL Lewis is generally credited with the synthesisof lewisite in 1918, although German scientists hadstudied this material earlier. 1,59,248–250 The United Statesmanufactured a large quantity for battlefield use andsent a shipload to Europe; however, World War Iended while the shipment was at sea, and the vesselwas sunk. 1,250No battlefield use of lewisite has been verified,although Japan may have used it against Chinabetween 1937 and 1944. 246 Lewisite is probably inthe chemical warfare stockpile of several countries.Lewisite is sometimes mixed with mustard to lowerthe freezing point of mustard; Russia has stores ofthis mixture. 251PropertiesPure lewisite is an oily, colorless liquid, and impurelewisite is amber to black. It has a characteristic odorof geraniums. Lewisite is much more volatile andpersistent in colder climates than mustard. Lewisiteremains fluid at lower temperatures, which makes itperfect for winter dispersal. Lewisite hydrolyzes rapidly,and, on a humid day, maintaining a biologicallyactive concentration of vapor may be difficult. 252LewisiteToxicityThe toxicity of lewisite vapor is very similar to thatof mustard vapor. Vesication is caused by 14 µg ofliquid. 98,250 Blister fluid from a lewisite-caused blisteris nonirritating; however, it does contain 0.8 to 1.3mg/mL of arsenic. In some instances intact lewisiteor equally damaging breakdown products have beenfound in blister fluid. 59,250Biochemical Mechanisms of InjuryLewisite shares many biochemical mechanisms ofinjury with the other arsenical compounds. It inhibitsmany enzymes, in particular, those with thiol groupssuch as pyruvic oxidase, alcohol dehydrogenase, succinicoxidase, hexokinase, and succinic dehydrogenase(Figure 8-15). As is true with mustard, the exactmechanism by which lewisite damages cells has notbeen completely defined. Inactivation of carbohydratemetabolism, primarily because of inhibition of thepyruvate dehydrogenase complex, is thought to be akey factor. 250Clinical EffectsLewisite damages skin, eyes, and airways by directcontact and has systemic effects after absorption. Unlikemustard, it does not cause immunosuppression.Data on human exposure are few. Lewisite was appliedto human skin in a few studies; however, mostinformation on its clinical effects is based on animalstudies. 59,253–255SkinReactions withGlutathione• Loss of protein thiol status• Loss of Ca ++ homeostais• Oxidation stress• Lipid periodation• Membrane damage• Cell death• Acute tissue injuryReactions with AdjacentSulfhydryl Groups of Enzymes• Inhibition of pyruvate• dehydrogenase complex• Inhibition of glycolysis• Loss of ATP• Cell death• Acute tissue injuryFig. 8-15. The putative mechanisms by which lewisite causestissue damage.ATP: adenosine triphosphateCa++: calcium ionsAdapted from: US Army Medical Research Institute ofChemical Defense. A global picture of battlefield vesicants,I: a comparison of properties and effects. Med Chem Def.1992;5(1):6.Lewisite liquid or vapor produces pain or irritationwithin seconds to minutes after contact. Pain caused bya lewisite lesion is much less severe than that causedby mustard lesions, and it diminishes after blistersform. 59 Erythema is evident within 15 to 30 minutesafter exposure to liquid lewisite, and blisters startwithin several hours; these times are somewhat longerafter vapor exposure. Lewisite is absorbed by the skinwithin 3 to 5 minutes (compared with 20 to 30 minutesfor an equal amount of mustard) and spreads over awider area than the same amount of mustard. Thelewisite blister begins as a small blister in the centerof the erythematous area and expands to include theentire inflamed area, whereas vesication from mustardbegins as a “string of pearls” at the periphery of thelesion, and the small blisters eventually merge. 59 Otherdifferences between the lesions produced by these twochemical agents are as follows:292
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<strong>Medical</strong> <strong>Aspects</strong> <strong>of</strong> <strong>Chemical</strong> <strong>Warfare</strong>Military UseA research team headed by US Army CaptainWL Lewis is generally credited with the synthesis<strong>of</strong> lewisite in 1918, although German scientists hadstudied this material earlier. 1,59,248–250 <strong>The</strong> United Statesmanufactured a large quantity for battlefield use andsent a shipload to Europe; however, World War Iended while the shipment was at sea, and the vesselwas sunk. 1,250No battlefield use <strong>of</strong> lewisite has been verified,although Japan may have used it against Chinabetween 1937 and 1944. 246 Lewisite is probably inthe chemical warfare stockpile <strong>of</strong> several countries.Lewisite is sometimes mixed with mustard to lowerthe freezing point <strong>of</strong> mustard; Russia has stores <strong>of</strong>this mixture. 251PropertiesPure lewisite is an oily, colorless liquid, and impurelewisite is amber to black. It has a characteristic odor<strong>of</strong> geraniums. Lewisite is much more volatile andpersistent in colder climates than mustard. Lewisiteremains fluid at lower temperatures, which makes itperfect for winter dispersal. Lewisite hydrolyzes rapidly,and, on a humid day, maintaining a biologicallyactive concentration <strong>of</strong> vapor may be difficult. 252LewisiteToxicity<strong>The</strong> toxicity <strong>of</strong> lewisite vapor is very similar to that<strong>of</strong> mustard vapor. Vesication is caused by 14 µg <strong>of</strong>liquid. 98,250 Blister fluid from a lewisite-caused blisteris nonirritating; however, it does contain 0.8 to 1.3mg/mL <strong>of</strong> arsenic. In some instances intact lewisiteor equally damaging breakdown products have beenfound in blister fluid. 59,250Biochemical Mechanisms <strong>of</strong> InjuryLewisite shares many biochemical mechanisms <strong>of</strong>injury with the other arsenical compounds. It inhibitsmany enzymes, in particular, those with thiol groupssuch as pyruvic oxidase, alcohol dehydrogenase, succinicoxidase, hexokinase, and succinic dehydrogenase(Figure 8-15). As is true with mustard, the exactmechanism by which lewisite damages cells has notbeen completely defined. Inactivation <strong>of</strong> carbohydratemetabolism, primarily because <strong>of</strong> inhibition <strong>of</strong> thepyruvate dehydrogenase complex, is thought to be akey factor. 250Clinical EffectsLewisite damages skin, eyes, and airways by directcontact and has systemic effects after absorption. Unlikemustard, it does not cause immunosuppression.Data on human exposure are few. Lewisite was appliedto human skin in a few studies; however, mostinformation on its clinical effects is based on animalstudies. 59,253–255SkinReactions withGlutathione• Loss <strong>of</strong> protein thiol status• Loss <strong>of</strong> Ca ++ homeostais• Oxidation stress• Lipid periodation• Membrane damage• Cell death• Acute tissue injuryReactions with AdjacentSulfhydryl Groups <strong>of</strong> Enzymes• Inhibition <strong>of</strong> pyruvate• dehydrogenase complex• Inhibition <strong>of</strong> glycolysis• Loss <strong>of</strong> ATP• Cell death• Acute tissue injuryFig. 8-15. <strong>The</strong> putative mechanisms by which lewisite causestissue damage.ATP: adenosine triphosphateCa++: calcium ionsAdapted from: US Army <strong>Medical</strong> Research Institute <strong>of</strong><strong>Chemical</strong> Defense. A global picture <strong>of</strong> battlefield vesicants,I: a comparison <strong>of</strong> properties and effects. Med Chem Def.1992;5(1):6.Lewisite liquid or vapor produces pain or irritationwithin seconds to minutes after contact. Pain caused bya lewisite lesion is much less severe than that causedby mustard lesions, and it diminishes after blistersform. 59 Erythema is evident within 15 to 30 minutesafter exposure to liquid lewisite, and blisters startwithin several hours; these times are somewhat longerafter vapor exposure. Lewisite is absorbed by the skinwithin 3 to 5 minutes (compared with 20 to 30 minutesfor an equal amount <strong>of</strong> mustard) and spreads over awider area than the same amount <strong>of</strong> mustard. <strong>The</strong>lewisite blister begins as a small blister in the center<strong>of</strong> the erythematous area and expands to include theentire inflamed area, whereas vesication from mustardbegins as a “string <strong>of</strong> pearls” at the periphery <strong>of</strong> thelesion, and the small blisters eventually merge. 59 Otherdifferences between the lesions produced by these twochemical agents are as follows:292