Page 85 - Journal of Special Operations Medicine - Fall 2017

Atropine Eye Drops

A Proposed Field Expedient Substitute in the Absence of Atropine Autoinjectors

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1
Christopher J. Calvano, MD, PhD* ; Robert W. Enzenauer, MD, MPH, MBA, MSS ;
Derek Eisnor, MD, ABEM, ABMT ; Robert A. Mazzoli, MD 4
3

ABSTRACT
Nerve agents are a threat to military and civilian health. The trials are lacking in the published literature. Still, the papers
antidote, atropine sulfate, is delivered by autoinjector, which we cite in this article show there is an identified need for alter-
is a limited resource. We propose the use of 1% atropine oph- native to the autoinjector.
thalmic solution (supplied commercially in 5mL or 15 mL
bottles) via oral, ocular, and intranasal administration as an We propose, based on the known safety profile of atropine
expedient substitute in austere environments. and the similar bioavailability of oral versus IM ROA, that the
widely commercially available 1% AS ophthalmic solution be
Keywords: nerve agent; chemical warfare; atropine; antidote; considered as an expedient substitute. Our rationale follows.
alternative treatment
AS 1% ophthalmic solutions are available in 5mL or 15mL
vials. A 1% solution contains 10mg of drug/solute in each
1mL of vehicle. Therefore, a commercial 5mL vial of 1% AS
Introduction
would contain 50mg of drug (a 15mL vial contains 150mg of
The threat of chemical weapons exposure including nerve AS). This would be the equivalent of 25 or 75 autoinjectors
agents is both real and well documented in current global con- for a 5mL or 15mL vial, respectively, assuming bioavailability
flicts affecting U.S. military and civilian personnel. Depart- parity. Given that each drop from the vial is approximately
1
ment of Defense (DoD) personnel deployed to at-risk theaters 50μL and contains 0.5mg of AS, we can postulate that 4 drops
are routinely issued atropine autoinjectors. These automated would deliver 2mg of AS. This would be equivalent to the au-
devices deliver 2mg of atropine sulfate (AS) in 0.7mL of vehi- toinjector, which provides 2mg of drug in 0.7mL of vehicle.
cle; a second injector delivers 600mg of pralidoxime (2-PAM) Because 1mg of AS is equivalent to 0.84mg of atropine base,
in 2mL of vehicle. There are, however, well-documented the net predicted drug delivered by ophthalmic drops would
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manufacturer supply issues that affect the efficacy of injectors be 84% of expected (4 drops = 200μL of AS = 2mg of AS =
for end users. As recently as 2013, there were acknowledged 1.64mg of atropine base).
defects in injectors supplied to the DoD, including incomplete
doses and mechanical failure. 3 Alternative ROAs proposed are either sublingual or direct
to the buccal or intranasal mucosa. Bioavailability is defined
An alternative to the atropine autoinjector is desirable, given as the percentage of a given dose that ultimately reaches the
the likelihood of a mass casualty event involving organophos- target organ site. Ideal bioavailability is equal to 1.00. Most
phates or nerve agents. Whether due to industrial (insecticide ROAs see a decrease in bioavailability to less than 1.00 due to
or chemical manufacturing) or intentional deployment of factors including the first-pass effect for oral administration,
nerve agent, first responders may quickly exhaust their sup- limited absorption for transcutaneous or inhalation, and the
plies of injectors—if they have them at all. Local antidote re- need for bioactivation of a prodrug via hepatic metabolism.
sources would be long exhausted before the arrival of Strategic
National Stockpile push-packs (up to 12 hours before deliv- Lacrimal punctal occlusion is often suggested for the use of
ery) in the event of any significant civilian chemical disaster, ophthalmic topical medications (e.g., β-blockers for glau-
making the use of local pharmaceutical resources essential. 4 coma treatment) to minimize systemic absorption and sub-
sequent adverse effects. We can exploit systemic absorption
Several attempts to formulate and test alternatives to intra- of ophthalmic drugs via the ocular conjunctiva, lacrimal, or
5,6
muscular (IM) injection have included sublingual tablets, intranasal muscosal surfaces to generate intentional systemic
intraosseous infusion, and nasal drops and nanoparticle distribution and therapeutic effect. In a setting of nerve agent
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powders for inhalation. However, none of these strategies exposure and depending on the dose of agent and time after
5,8
have yet to gain widespread acceptance. Bioavailability has exposure, hypersalivation and emesis could predictably de-
been shown to be a match for the IM route of administration crease or block absorption of an oral dose of atropine solu-
(ROA), but gold standard randomized, double-blind clinical tion. Increased nasolacrimal and pulmonary secretions also
*Correspondence to christopher.j.calvano.mil@mail.mil
1 MAJ Calvano is the current USAR Ophthalmology Consultant to the Surgeon General and is a toxicologist. He is also an assistant professor of
Ophthalmology, Department of Medical Education, University of Central Florida. BG (Ret) Enzenauer is chief of pediatric ophthalmology at
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Children’s Hospital Colorado/University of Colorado. Dr Eisnor is a former Air Force physician and board-certified medical toxicologist and
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emergency physician who works with multiple defense and government entities. COL (Ret) Mazzoli is an oculoplastic and ophthalmic surgeon
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currently at the Vision Center for Excellence at Madigan Army Medical Center.
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