Advances in Medical Countermeasures for Chemical Terrorism

The notorious 1995 Aum Shinrikyo terrorist attack on the Tokyo subway system that used sarin nerve agent to kill or injure a number of innocent citizens was a small but well publicized example of the major impact that even a relatively “minor” chemical-weapons incident can have on a major metropolitan area – and an entire nation. The fanatical religious/terrorist group had managed to produce a small quantity of sarin, deliver it in a simple way, and create widespread damage that resulted in 12 deaths and an estimated 50 or so serious injuries.

Hundreds of other people were directly exposed, though, and thousands more sought emergency care – most of them out of fear – as a precautionary measure. The attack, although tragic, had the potential to be much worse.

The one consolation for Japan and many other equally vulnerable nations is that what is now simply called “the Aum Shinrikyo incident” provides a small but enlightening glimpse into the numerous and unique challenges likely to be involved in responding to a much larger and better orchestrated terrorist attack, particularly one using chemicals.

The Challenges Posed by Chemical Terrorism

The management of a chemical terrorism response must take into consideration a wide range of challenges – involving, for example, responder health and safety, detection and analysis of the specific chemical agent(s) used, isolation and/or decontamination of patients, and diagnosis and treatment of victims. In recent years, fortunately, important progress has been made in dealing with numerous other types of mass-casualty incidents, both natural and manmade. Most responder agencies know how to cope effectively with hazmat (hazardous materials) spills and incidents.

Today, the weakest link in chemical terrorism preparedness, in most if not all political jurisdictions, is the medical component. Nonetheless, many chemical threats – including an array of toxic industrial chemicals that may be accidentally or intentionally released from a train, truck, or even a fixed facility – generate relatively common syndromes that the medical community is already fairly well trained and equipped to manage.

Industrial sources and many chemical weapons cause several types of toxic trauma such as respiratory failure, pulmonary edema (fluid accumulation in the lungs), and burns on the skin and mucous membranes. Although both physically and psychologically challenging, these are not uncommon conditions for well-trained clinicians to manage. However, there are certain chemicals that pose greater and immensely more difficult challenges, particularly in relation to the treatment(s) needed and/or readily available. Two particularly challenging chemical treatments involve organophosphorous agents and insecticides (nerve agents).

One year after the 11 September 2001 terrorist attacks against the United States, a new program was launched by the Strategic National Stockpile (SNS), a division of the U.S. Centers for Disease Control and Prevention (CDC), to address mounting concerns that future terrorist attacks might well include the use of nerve agents. What came to be known as the CHEMPACK Program led to the pre-positioning – in communities large and small throughout the United States – of nerve agent antidotes. Eventually, more than 1,600 containers – each of them packed with hundreds of antidote doses – were distributed to political jurisdictions in every state and major city throughout the country. The SNS rationale was both clear and logical: (1) to give local responders closer and better control; and (2) to decrease response times as much as possible – without compromising security.

Containers & Antidotes; Nerve Agents & the Time Factor

There are two types of containers fielded: (a) EMS (Emergency Medical Services) containers, primarily made up of auto-injectors designed for the rapid treatment of exposed populations in the field; and (b) hospital containers, which are tailored more for clinical care and consist mostly of multi-dose vials of antidotes. Both types of containers store all three of the drugs used, in combination, as the antidote for nerve agent exposure: atropine, pralidoxime chloride, and diazepam. The containers are strategically positioned in communities selected by the CDC in coordination with local officials. Each container is maintained under secure and very tightly controlled environmental conditions. All containers are monitored constantly, a precautionary requirement that not only improves safety but also helps assure the shelf life of the drugs.

In addition to commercial organophosphorus insecticides, there are four principal “nerve agents”: sarin, soman, tabun, and VX. All nerve agents attack and weaken or destroy the body’s neurological system – in two ways: (a) through the agents’ muscarinic effects on the glands (which are characterized as muscle twitching or jerking, followed by seizures or paralysis); and (b) through nicotinic effects on the skeletal muscles, which are characterized by increased salivation, watery eyes, runny nose, and an increased flow of mucous (which leads to coughing, wheezing, difficulty in breathing, diarrhea, and involuntary urination).

These symptoms are controlled by first using the drug atropine. As it blocks the effects caused by excess acetylcholine, the patient will become more “dry” and have less difficulty breathing. The administration of atropine is immediately followed by administering a second type of drug, pralidoxime chloride, which can break the bond between the nerve agent and the neurological system by reactivating acetyl cholinesterase and reducing the levels of acetylcholine, thus ameliorating the symptoms. Finally, in severely exposed patients, diazepam also may be administered – primarily to decrease the severity of symptoms caused by the acetylcholine-induced seizures.

The same three drugs comprise the complete antidote for nerve agent exposure and, for that reason, have been a principal focus of U.S. efforts to upgrade and improve the nation’s overall chemical terrorism preparedness capabilities.

Because time is so critical in the administration of nerve agent antidotes, a kit was developed decades ago for field military use to rapidly inject the drugs. The kit contains two auto-injectors: (a) a small injector containing atropine; and (b) a larger one containing pralidoxime chloride. Not only do the auto-injectors provide a rapid, spring-loaded injection, they also deliver the drugs with enough force to diffuse them, quickly and safely, into the muscle tissue for rapid uptake by the body. During a mass-casualty response involving a nerve agent, the speed at which an antidote is delivered is perhaps the most critical factor in determining the overall severity of an injury or disabling medical condition. The auto-injector technology now available enables first responders to treat a large number of exposed individuals in the field much more rapidly than was ever previously possible.

A Two-in-One Solution: The Dual-Chambered Auto-Injector

In recent years, this new rapid-delivery process has been cut in half through the development of a dual-chambered auto-injector containing both atropine and pralidoxime chloride. When the device is activated (usually by pressing it against the victim’s thigh), it delivers one drug from the first chamber as the needle proceeds through the thigh tissue and, after that chamber is fully extended, continues the flow by starting the other drug from the second chamber. For practical purposes, two rapid injections are given with one needle, in one quick auto-injection, while at the same time keeping the drugs safely separated within the tissue.

The necessity to properly train and frequently exercise EMS responders and/or hospital providers in the CHEMPACK sequence cannot be emphasized too strongly. Any lack of program awareness among responders could significantly delay fielding of the nerve-agent antidote and result in critical minutes being lost. Training providers to quickly recognize the unique clinical signs indicative of nerve agent exposure is particularly important for assuring rapid treatment. After the ability to quickly diagnose is refined and the logistics of fast deployment are established, focus will turn to the safe use of auto-injectors.

An important cautionary note: Despite current training methods, and notwithstanding the clear directions printed on the device, it is not uncommon for responders to initially flip the device backward. This almost reflexive action is partly due to the fact that the safety cap of the auto-injector is on the back side of the device, in a better position to release the activation mechanism – instead of on the front of the device to shield the needle itself, as is common on syringes. The real danger is that, if a healthcare worker puts his or her thumb over the end of the device (to apply pressure more quickly), that action might well activate the needle through the person’s thumb. Consequently, training should always emphasize the proper handling of the device – namely, make a fist without placing a thumb on the end.

The CHEMPACK program has significantly enhanced U.S. preparedness to cope with a nerve agent terrorist attack and/or an industrial accident involving organophosphorus insecticides. The fielding of this antidote is therefore an important step forward in chemical terrorism preparedness. As is required and expected in the treatment of nerve agents, any antidote must be available very quickly so that it may be administered before a permanent injury occurs. By allowing stock to be rotated and expanding the use of medical countermeasures, public health preparedness capabilities will benefit on an even broader scale in the foreseeable future.

For additional information on: The CHEMPACK Program, visit the U.S. Department of Health and Human Services, Chemical Hazards Emergency Medical Management website at

Bruce Clements

Bruce Clements is the Public Health Preparedness Director for the Texas Department of State Health Services in Austin, Texas, and in that post is responsible for health and medical preparedness and response programs ranging from pandemic influenza to the health impact of hurricanes. A well-known speaker and writer, he also serves as adjunct faculty at the Saint Louis University Institute for BioSecurity. His most recent book, Disasters and Public Health: Planning and Response, was released in 2009.



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