Acetylcholinesterase inhibitors (AChEIs) are xenobiotics that bind acetylcholinesterase, the enzyme responsible for breakdown of acetylcholine. ^{Reference Vanderah, Pappano, Katzung and Vanderah1} AChEIs chemical groups are classified as quaternary alcohols, carbamates, and organophosphates (OPs), with the latter having the most potential for human harm. With industrial exposures, intentional overdoses, or as a chemical weapon, AChEIs can lead to an overwhelming accumulation of acetylcholine in the peripheral and central nervous systems. ^{Reference Suchard, Nelson, Howland and Lewin2}

Since World War I, there has been a significant expansion in the use of the subcategory of OPs referred to as nerve agents for the purpose of chemical warfare. Nerve agents began to be mass-produced as chemical weapons by Nazi Germany during World War II, and since then, second-, third-, and fourth-generation agents have been developed. ^{Reference Vale, Marrs and Maynard3} Fourth-generation agents are the most potent nerve agents known to date, and are sometimes referred to as Novichoks (“newcomer” in Russian).

The use of a nerve agent in a chemical attack, although rare, has the potential for catastrophic morbidity and mortality, as seen with the 1995 Tokyo sarin attack that injured over 5000 people. ^{Reference Tokuda, Kikuchi and Takahashi4} The CHEMPACK program was created as part of the Strategic National Stockpile and was designed for the forward placement of the necessary antidotes in the setting of a potential large-scale nerve agent attack in the United States. ^{Reference Madsen and Greenberg5} The possibility of terror attacks, particularly in New York City (NYC), proves the need for defense measures against chemical, biological, radiological, and nuclear (CBRN) agents. Since the 9/11 terror attacks occurred in NYC in 2001, NYC hospitals have prioritized CBRN planning across several sectors including law enforcement, fire department, emergency medical services, public health, and health-care stakeholders. Additionally, after several recent reports of poisoning using fourth-generation agents, health-care facilities renewed their interest in becoming better prepared for nerve agent exposure response. ^{Reference Vale, Marrs and Maynard3}

Because of the infrequency of CBRN events, preparation is critical and an ongoing challenge for health-care and emergency systems to ensure proper response to a mass casualty incident (MCI) involving hazardous agents. ^{Reference Tokuda, Kikuchi and Takahashi4,Reference Siman-Tov, Davidson and Adini6} One of the most well prepared countries for CBRN response due to previous and ongoing conflicts is Israel. ^{Reference Suchard, Nelson, Howland and Lewin2} In a review of MCI emergency preparedness in 23 acute care hospitals in Israel, a high rate of staff knowledge was observed for responding to rare events such as toxicological and biological attacks. ^{Reference Siman-Tov, Davidson and Adini6} This was despite most health-care workers in the system not having practical experience responding to such events. The review noted that each emergency department (ED) is supplied with information sheets with the management for each type of hazard immediately accessible to them to avoid clinicians having to recall from memory or spend time finding resources.

Effective hospital disaster preparedness should engage multiple stakeholders along with ancillary departments and external agencies. The pharmacy department may be an underused resource when engaging in MCI planning. ^{Reference Krajewski, Sztajnkrycer and Báez7} In addition to ensuring proper antidote stocking, storage, and dispensing in the event of an occurrence, pharmacy resources can be accessed to supplement clinical support for antidote management strategies. Because of the rarity of such an event, many institutions may not have a standardized dosing tool for OP incident management.

Methods

Our institution is a busy, 450-bed, academic Level 1 Trauma Center in NYC accustomed to unpredictable patient surges and multiple triage events including motor vehicle accidents, gunshot wounds, and multi-dwelling fires. Due to the urban location of the hospital, as well as proximity of the surrounding industrial areas, leadership has prioritized chemical event planning.

In the planning stage for a chemical incident MCI drill, it was proposed that medical staff would benefit from having a succinct antidote-dosing tool to rapidly disseminate during the drill. While the Centers for Disease Control and Prevention (CDC) maintains a job aid website for initial emergency department treatment, the algorithm does not differentiate between mild/moderate and severe manifestations, or provide detailed administration instructions and guidance. ⁸ Moreover, in a true nerve agent attack, it is reasonable to anticipate that medical staff may be overwhelmed with the additional task of locating an antidote dosing guide, while attempting to manage an unpredictable patient volume and acuity level under extreme psychological stress. Furthermore, in a catastrophic attack, Internet or online resources may be inaccessible. In collaboration with the full-scale exercise (FSE) planning team, the clinical pharmacist developed an antidote-dosing guide to use for the planned MCI chemical agent drill.

The dosing guide was created to be a 2-sided 1-page tool (Figure 1). Information provided on the first side included examples of nerve agents, personal protective equipment warnings, and pharmacy contact numbers. The tool included antidote-related pharmacotherapy information such as mechanisms of action, concentrations supplied, and administration instructions and goals of therapy for the primary used antidotes and therapies including atropine, pralidoxime, and benzodiazepines.

Figure 1. Nerve Agent Antidote-Dosing Tool

The second page was modeled after dosing guidance provided by the NIH (National Institutes of Health) and CDC, with additional therapeutic considerations added to the dosing guide. ^{Reference Suchard, Nelson, Howland and Lewin2,8–Reference Markenson and Redlener10} Treatment recommendations were stratified by level of toxicity and symptomology, as well as by age and weight. The pharmacy department maintains a 24/7 decentralized pharmacy satellite in the ED. Physical copies of the dosing guide were kept with stocked antidotes in the ED satellite, and as a supplement to the MCI Response Toolkit.

Antidote supplies were reviewed and doses calculated for an estimated initial patient influx to treat such an incident. Based off this review, our pharmacy department optimized par levels of stored antidotes to ensure adequate amounts for emergent treatment before the receipt of a theoretical authorized CHEMPACK distribution.

This exercise did not involve patient subjects and was exempt from Institutional Review Board (IRB) review.