Military Implications of Atropine Hypersensitivity

Military Medicine, May 2004 by Hague, Jenifer D, Derr, Jeffrey J

Atropine hypersensitivity is a rarely reported condition. However, in the military environment, such reactions are of significant concern given the threat of chemical warfare and the use of atropine as a nerve agent antidote. Upon deployment to regions where chemical attacks are a threat, each service member is issued three 2-mg intramuscular autoinjectors of atropine for self-treatment. In the case presented here, an active duty service member presented to his Aid Station to request red dog tags for a previously identified allergy to atropine. Sensitivity testing revealed a significant reaction to

Introduction

Atropine allergy or sensitivity is a rarely recognized condition that has serious implications for military deployability and suitability. Through increased awareness, alternative treatments or standard policy could be developed for military members with atropine sensitivity that face chemical warfare threats.

Case Report

A 21-year-old Caucasian man presented to his military medical facility to request red dog tags for his reported allergy to atropine. Upon questioning, the patient reported that at the age of 7, he underwent a routine dilated eye examination while living in the Ukraine. Approximately 20 minutes after his eyes were dilated, the patient reported that he began shaking and became unresponsive. At that time, he was taken to the emergency room for monitoring, and no resuscitation was required. After the event, the patient was told he was allergic to the atropine in the eye drops. As a result of ongoing training and increased media coverage of the threat of chemical weapons before a deployment in support of Operation Enduring Freedom, the military member recognized the importance of atropine in the treatment of nerve agent poisoning and requested red dog tags to avoid inadvertent exposure to the drug. Because of the unusual nature of the described reaction and the implications for military service, further investigation was initiated. The patient was referred to an allergist, where an atropine challenge was performed in a monitored setting. The patient was prick tested with 0.01% atropine followed by 0.1%, with negative results. Incremental intradermal testing of 0.01% atropine and 0.1% initially resulted in an irritant skin reaction. However, within 15 minutes of the final 0.1% intradermal test, the patient began to experience signs of atropine poisoning that included twitching, flushed skin, dilated pupils, tachycardia, rapid deep breathing, and altered sensorium. He recovered after the administration of 3 mg of physostigmine.

It is estimated that the patient received a total of 0.02 to 0.03 mg of atropine during the test, and therapeutic doses for a chemical attack can exceed 5 mg. Therefore, in a chemical warfare environment where nerve agents are used, this military member is at risk from both the nerve agent and its antidote.

Discussion

The above case demonstrates that very small doses of atropine can result in severe adverse reactions in sensitive individuals. Adverse reactions after administration of subtherapeutic doses of medications are likely allergic or idiosyncratic. In this case, the reaction appears to be idiosyncratic because the patient exhibited signs and symptoms of atropine toxicity at doses approximately 100 times less than the usual therapeutic dose after nerve agent exposure. The reaction resolved with physostigmine, an acetycholinesterase inhibitor, and did not require the administration of epinephrine or other usual treatments for anaphylaxis.

Idiosyncratic "Toxic" Reactions

Gallasch et al.1 described 31 pediatric patients who developed local and systemic signs of atropine toxicity after the administration of atropine eye drops for the purpose of assessing refraction. Systemic signs included increased temperature and diffuse dry red skin. Two patients developed periorbital dermatitis. In all cases, skin testing was negative for atropine allergy, and local and systemic toxic effects to relatively low doses of atropine in eye drops was suspected.

Case reports suggest a wide variation in physiologic response to atropine when administered to a large population. A report in the ophthalmology literature described a toxic reaction in a child resembling the reaction in this case, although it was likely due to a larger dose much closer to the toxic range.2 However, a widely variable toxic range is noted in their review, with an average lethal dose after eye drop instillation of about 100 mg (200 drops of 1% atropine), but there was also a case report of one patient recovering after a parenteral 1-g dose. In a survey of South Carolina ophthalmologists, one case of fever, two episodes of acute asthma exacerbation, and one seizure were noted after atropine instillation in the office setting over a 2-year period.3 Assuming no accidental overadministration, these cases demonstrate the capability of a therapeutic dose to cause symptoms consistent with atropine overdose in sensitive individuals. Cases demonstrating similar hypersensitivity to perioperative therapeutic parenteral doses of atropine have been described, including one incident where a patient developed tachycardia, hypertension, vision disturbance, mydriasis, and a central nervous system (CNS) disturbance that responded to neostigmine.4