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

Nerve AgentsTABLE 5-11EFFECTS OF PYRIDOSTIGMINE PRETREAT-MENT* ON US SOLDIERS IN THE PERSIANGULF WAREffect Incidence (%)N=41,650Gastrointestinal symptoms≤50Urinary urgency and frequency 5–30Headaches, rhinorrhea, diaphoresis,tingling of extremities< 5Need for medical visit < 1Discontinuation on medical advice < 0.1*Dose was 30 mg pyridostigmine bromide, administered orally every8 hours for 1 to 7 days.Adapted with permission from: Keeler JR, Hurst CG, Dunn MA.Pyridostigmine used as a nerve agent pretreatment under wartimeconditions. JAMA. 1991;266:694.were also experiencing a wide range of other wartimerelatedstresses, such as repeatedly donning and removingtheir chemical protective suits and masks inresponse to alarms, sleep deprivation, and anticipationof actual combat. Because there was no comparablegroup of soldiers undergoing identical stresses but notadministered pyridostigmine, it is not clear to whatextent pyridostigmine itself was responsible for thesymptoms noted above. The findings are thus a worstcaseestimate for effects attributable to pyridostigmineuse in wartime.Among these soldiers, less than 1% sought medicalattention for symptoms possibly related to pyridostigmineadministration (483 clinic visits). Most of thesehad gastrointestinal or urinary disturbances. Twosoldiers had drug rashes; one of them had urticariaand skin edema that responded to diphenhydramine.Three soldiers had exacerbations of bronchospasm thatresponded to bronchodilator therapy. Because the unitsof the XVIII Airborne Corps had been deployed to adesert environment for 5 months before pyridostigminewas used, most soldiers with significant reactiveairways disease had already developed symptomsand had been evacuated earlier. The consensus amongmedical personnel more recently arrived was thatthey saw more pyridostigmine-related bronchospasmin their soldiers who had not been present in theateras long. Later, many soldiers said that they simplystopped taking the medication and did not reportsymptoms to their medical officers. 269Because of increased exposure to the work-of-breathing requirements of being masked, as well asinhaled dust, smoke, and particles, it was unclearwhether pyridostigmine was a major causative factorin those who had bronchospasm at the onset of hostilities.Two soldiers from the XVIII Airborne Corps hadsignificant blood pressure elevations, with diastolicpressures of 110 to 120 mm Hg, that manifested asepistaxis or persistent bleeding after a cut and subsidedwhen pyridostigmine was stopped. Anothersoldier who took two pyridostigmine tablets togetherto make up a missed dose experienced mild cholinergicsymptoms, self-administered an atropine autoinjector,and recovered fully after several hours. There were nohospitalizations or medical evacuations attributableto pyridostigmine among XVIII Airborne Corps soldiers.In other units, at least two female soldiers, bothweighing approximately 45 to 50 kg, noted increasedsalivation, muscular twitching, severe abdominalcramps, and sweating that prompted medical observation.The symptoms subsided after pyridostigminewas stopped. This experience suggests that cholinergicsymptoms may occur in a small number of individualswith relatively low body weight.In a group of 213 soldiers in Israel who took pyridostigmine(30 mg every 8 h), 75% reported at least onesymptom. 270 Included among these symptoms wereexcessive sweating (9%), nausea (22.1%), abdominalpain (20.4%), diarrhea (6.1%), and urinary frequency(11.3%). In a smaller group of 21 soldiers, pseudocholinesterase(also called butyrocholinesterase, which isdiscussed later in this chapter) activity was the samein the 12 who were symptomatic and the 9 who werenot symptomatic. 40An Israeli soldier who developed cholinergic symptomsafter taking pyridostigmine was reported to havea genetic variant of serum butyrlcholinesterase. 271 Thevariant enzyme has low binding affinity for pyridostigmineand other carbamates. The authors of the reportsuggested that people who are homozygous for thevariant enzyme could therefore show exaggeratedresponses to anticholinesterase compounds. The soldierhad a history of prolonged apnea after receivingsuccinylcholine premedication for surgery. Peoplewith similar histories of severe adverse responses tocholinergic medications should be carefully assessedconcerning their potential deployability to combat,where they might face either a nerve agent threat orthe potential need for resuscitative surgery involvingemergency induction of anesthesia 265 using cholinergicmedications.Because pyridostigmine was used during thePersian Gulf War and troops were ordered to takeit, and because some returning troops have reportedunexplained medical symptoms, the possible role203