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

Nerve AgentsFig. 5-5. The Mark I kit with its two autoinjectors: the AtroPencontaining 2 mg atropine, labeled 1—indicating it isto be injected first—and the ComboPen containing 600 mg2-pyridine aldoxime methyl chloride (2-PAM Cl), labeled2—indicating it is to be injected second. The plastic clipkeeps both injectors together and serves as a safety for bothdevices. The kit is kept in a soft black foam holder that iscarried in the gas mask carrier.Reproduced with permission from: Meridian Medical TechnologiesInc, Bristol, Tenn.can be maintained by the individual receiving it. Therationale for this choice of dose was expressed in theunclassified portion of a classified document as follows:The dose of atropine which the individual servicemancan be allowed to use must be a compromise betweenthe dose which is therapeutically desirable and thatwhich can be safely administered to a nonintoxicatedperson. Laboratory trials have shown that 2 mg of atropinesulfate is a reasonable amount to be recommendedfor injection by an individual and that higher doses mayproduce embarrassing effects on troops with operationalresponsibilities.When given to a normal individual (one withoutnerve agent intoxication), a dose of 2 mg of atropinewill cause an increase in heart rate of about 35 beats perminute (which is not usually noticed by the recipient), adry mouth, dry skin, mydriasis, and some paralysis ofaccommodation. Most of these effects will dissipate in 4to 6 hours, but near vision may be blurred for 24 hours,even in healthy young patients. The decrease in sweatingcaused by 2 mg of atropine is a major, potentiallyharmful side effect that may cause some people whowork in heat to become casualties. For example, when35 soldiers were given 2 mg of atropine and asked towalk for 115 minutes at 3.3 mph at a temperature ofabout 83°F (71°F wet bulb), more than half droppedout because of illness or were removed from the walkbecause of body temperature of 103.5°F or above. Onanother day, without atropine, they all successfullycompleted the same march. 177The 6 mg of atropine contained in the three injectorsgiven each soldier may cause mild mental aberrations(such as drowsiness or forgetfulness) in some individualsif administered in the absence of nerve agentintoxication. Atropine given intravenously to healthyyoung people causes a maximal increase in the heartrate in 3 to 5 minutes, but other effects (such as dryingof the mouth and change in pupil size) appear later. Inone study, 178 when atropine was administered with theAtroPen, the greatest degree of bradycardia occurredat 2.5 minutes (compared with 4.3 min when administeredby standard needle-and-syringe injection); aheart rate increase of 10 beats per minute occurred at7.9 minutes (versus 14.7 min with needle-and-syringeinjection); and maximal tachycardia (an increase of 47beats per min) occurred at 34.4 minutes (comparedwith an increase of 36.6 beats per min at 40.7 min withneedle-and-syringe injection).Thus, the autoinjector is more convenient to usethan the needle and syringe, and it results in morerapid absorption of the drug. Needle-and-syringedelivery produces a “glob” or puddle of liquid inmuscle. The AtroPen, on the other hand, sprays theliquid throughout the muscle as the needle goes in.The greater dispersion of the AtroPen deposit resultsin more rapid absorption. It has not been determinedwhether the onset of beneficial effects in treating nerveagent intoxication corresponds to the onset of bradycardia,the onset of tachycardia, or to other factors.The FDA has recently approved a combined-doseautoinjector including both atropine and 2-PAM Cl.Bioequivalence was demonstrated in animal studies.The dose of atropine in the new product, designated bythe Department of Defense as the antidote treatmentnerve agent autoinjector (ATNAA), is 2.1 mg (Figure5-6). At the time of writing, this product awaits a productioncontract with an FDA-approved manufacturer;it is anticipated that the ATNAA will replace the olderMARK 1 kit by approximately 2008. Its tactical valueFig. 5-6. The antidote treatment nerve agent autoinjector(ATNAA) delivers 2.1 mg atropine and 600 mg 2-pyridinealdoxime methyl chloride (2-PAM Cl). The medications are inseparate compartments within the device and are expressedout of a single needle. The gray cap on the right end of theinjector is the safety.Reproduced with permission from: Meridian Medical TechnologiesInc, Bristol, Tenn.183