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

Medical Aspects of Chemical Warfareimportant effect of pyridostigmine deserves considerationby field anesthesiologists and anesthetists usingmuscle relaxants for anesthesia induction: dependingon the duration of muscle-relaxant administration,there may be either up- or down-regulation of postsynapticACh receptors. 265 Clinical assessment of the statusof neuromuscular transmission using a peripheralnerve stimulator should provide a basis for adjustingthe dose of both depolarizing and nondepolarizingmuscle relaxants to avoid an undesirable duration ofmuscle paralysis.Wartime UsePyridostigmine was used to protect soldiers froman actual nerve agent threat in the Persian Gulf War.United States and Allied decisions to use pyridostigminefollowed established doctrine, taking into accountIraqi capabilities and intentions. Iraq was knownto have substantial stocks of sarin and VX, for whichpyridostigmine pretreatment is unnecessary. However,Iraq was also known to be interested in acquiring anycompounds that might defeat Allied protection, suchas the rapidly aging nerve agent, soman. The securityof Warsaw Pact stocks of soman, for example, was agrowing concern in 1990.It was also known in 1990 that Iraq had begunlarge-scale production of GF, a laboratory compoundthat had not earlier been manufactured in weaponsquantity. International restrictions on the purchaseof chemical precursors of the better-known nerveagents may have led Iraq to acquire cyclohexyl alcohol,which it was then able to use to produce GF.Very limited data on medical protection against GFwere not reassuring. Although GF’s aging time withAChE was reported to be relatively long (see Table5-8), unpublished information from Allied countriessuggested that postexposure atropine/oxime therapyin rodents exposed to GF did not protect against theeffects of GF poisoning. As confirmed by the laterstudies shown in Table 5-10, atropine/oxime therapyonly provided rodents with PRs in the range of 1.4to 2.7. The only primate data available showed thatrhesus monkeys given pyridostigmine pretreatmentand atropine/oxime therapy uniformly survived a5-LD 50challenge with GF. 246 Concern about Iraq ’ s newGF capability, added to its known interest in acquiringsoman, made Allied use of pyridostigmine a reasonablecourse of action.Pyridostigmine bromide tablets, 30 mg, to be takenevery 8 hours, are currently maintained in stocks of UScombat units. The compound is packaged in a 21-tabletblister pack called the “nerve agent pyridostigminepretreatment set,” or NAPPS). One nerve agent pyridostigminetreatment set packet provides a week ofpyridostigmine pretreatment for one soldier. 182,183The decision to begin pretreatment with pyridostigmineis made by commanders at Army division levelor the equivalent, based on assessment of the nerveagent threat by their chemical, intelligence, and medicalstaff officers. 182,183,266 Because of the lack of data onlong-term administration of pyridostigmine to healthyadults, current doctrine calls for a maximum pretreatmentperiod of 21 days, with reassessment at frequentintervals of the need for continued pretreatment. Acommander may extend the period once, but requiresthe approval of the first general or flag officer in thechain of command.Pyridostigmine is poorly absorbed when takenorally; its bioavailability is 5% to 10%. 267 Ideally, twodoses of pyridostigmine, taken 8 hours apart, shouldbe administered prior to any risk of nerve agentexposure. 182,183,266 However, some benefit would beexpected even if the first pyridostigmine dose is takenan hour before nerve agent exposure. Because excessiveAChE inhibition can impair performance, no morethan one 30-mg tablet should be taken every 8 hours. Ifa dose is forgotten or delayed, administration shouldsimply be resumed on an 8-hour schedule as soon aspossible, without making up missed doses.In Operation Desert Storm in 1991, pyridostigminewas administered under combat conditions for thefirst time to US and Allied soldiers thought to be atrisk for nerve agent exposure. Data on safety and possibleadverse responses were collected from the unitmedical officers caring for the 41,650 soldiers of theXVIII Airborne Corps, who took from 1 to 21 doses ofpyridostigmine during January 1991. 268 Most majorunit commanders continued the medication for 6 to 7days, with over 34,000 soldiers taking it for that duration.They were able to perform their missions withoutany noticeable impairment, similar to findings withpeacetime volunteers participating in studies. 253 However,they reported a higher-than- expected incidenceof side effects, as noted in Table 5-11.Gastrointestinal changes included flatus, loosestools, and abdominal cramps that were noticeable butnot disabling. These side effects, together with urinaryurgency, were of sufficient intensity for many soldiersto associate them with the medication. In most soldiers,these changes were noticed within hours of taking thefirst tablet. In many, the effects subsided after a dayor two of administration, and in others they persistedas long as pyridostigmine was administered. Someunits adopted a routine of taking pyridostigmine withmeals, which was thought to minimize gastrointestinalsymptoms.Soldiers taking pyridostigmine during this period202