Historical Overview
There were over one million casualties from chemical weapons during World War I, leading to approximately 90,000 deaths, and untold morbidity and misery. Though chemical warfare was widely condemned and most nations have signed international treaties refusing to use chemical weapons, the unfortunate reality is that they have been used a number of times since World War IÑin 1935 by Italy against Ethiopia (mustard gas was sprayed from aircrafts), by Japan when they invaded China in 1936, by Egypt in the 1960s (phosgene and mustard gas by aerial bombs) in the Yemeni Civil War, and by Iraq during the Iran-Iraq war and on their own people, the Kurds (using sulfur mustard and nerve agents). More than 25 countries are thought to still be producing chemical warfare agents (CWA).
Unfortunately, CWAs have also been used by terrorists. The Japanese Aum Shinrikyo cult used sarin, a nerve agent, in a terrorist attack in Matsumoto in June of 1994, and again in the Tokyo subway system in March of 1995. It is the latter incident that has received much attention because of the number of people injured (over 5,000) and killed (12), and because the sect also had released anthrax in previous attacks and had produced other nerve and biologic agents. In addition, the agent was released in a subway. Subway systems are of great concern to planning agencies because there are massed concentrations of people at specific times and the sites have limited accessibility.
Though repugnant to all of us, it is not surprising that chemical weapons are used, purely on a cost-effectiveness basis. Conventional weapons (based on data from the 1960s) cost $2,000 to produce mass casualties per square kilometer, nuclear weapons cost $800, chemical weapons cost $600, and biologic weapons cost $1. Treating such chemical weapons, however, requires massive investment of medical resources to deal with results that are psychologically as or more devastating than any other weapon. In treating casualties, it is important to protect oneself, more so than in treating casualties from any other weapon of mass destruction. From an anesthesia perspective, patients who have been exposed to nerve agents or their antidotes may require modification of the anesthetic plan if they require surgery for other reasons.
One must also take into account that, because of the likelihood of an industrial accident, we may be more likely to see patients injured by chemical agents than by nuclear or biologic agents. The best example would be an industrial accident in which large amounts of chlorine were released either from an explosion, a train derailment, or truck crash.
Chemical Agents
There are four main groups of CWAs (Table 1). The chemical weapons, in addition to their generic names with which we are familiar, also have military-designated codes. Volatility must be taken into account when discussing these agents. Most of these chemicals are in liquid form at standard temperature and pressure (STP). Phosgene and cyanide are the most volatile, while the volatility of sarin, interestingly enough, is similar to that of water. Sulfur mustard and soman (VX) are the least volatile. When vaporized, with the exception of hydrogen cyanide, all are heavier than air and concentrate in trenches, basements, or foxholes. If exposed, individuals should ascend to higher levels within a subway system or building; one should avoid low-lying areas. Even standing can provide some protection as opposed to lying down.
Volatility is inversely related to the persistence of an agentÑthe more volatile, the quicker it evaporates and dissipates; the less volatile, the greater the persistence. Most industrial chemicals such as hydrochloric acid are relatively nonpersistent. Chemicals used for military use, however, tend to be persistent (e.g., VX or sulfur mustard). The more persistent an agent, the more likely it is to penetrate the dermis and to result in greater injury. These agents, therefore, also pose the greatest threat to paramedics and emergency medical personnel.
Toxicity is also an important component. In terms of toxicity, i.e., in mg/min/m2, soman > sarin > sulfur mustard > cyanide > phosgene > chlorine. We are used to terms such as mean effective dose (ED50) or mean lethal dose (LD50), but chemical agents are also discussed as a concentration-time (Ct) product. Ct takes into account the concentration of an agent in the atmosphere factored by the amount of time that an individual is exposed to that concentration and expressed as mg/min/m3. An LD50 relates to dose and the LCT50 relates to exposure. Dose does not equal exposure.
A final factor that must be taken into account is time of onset, i.e., latency. Mustard, phosgene, and chlorine have the longest latency, whereas the nerve and blood agents have the shortest onset times, usually within seconds to minutes.
General Principles of Treatment
In a situation in which there is chemical exposure, one must clearly demarcate the contaminated zone, there must be protected entry and exit points, and there must be procedures in place and resources available to protect oneself and to decontaminate patients.
Self-Protection
Depending on the nature of the injury, if it is a pulmonary agent one must wear a “self-protective mask” (gas mask). If dealing with a nerve agent or vesicant, a chemical-protective suit must be worn. If healthcare providers care for a patient who has been exposed to any of these classes of compounds, they may acquire the agent on their skin or through latex gloves and become a casualty. The best protection is from a chemical-protective garment that is impermeable to all classes of agents.
Decontamination
In the event of any such large scale use of chemical weapons, there are specialized teams throughout the United States that would respond and facilitate decontamination. All hospitals, however, as part of their disaster preparedness plan, should have decontamination facilities available, especially those hospitals situated close to large chemical plants. In addition, antidotes to specific agents should be readily available (see below). Such antidotes would be in one of the 8 national pharmaceutical stockpiles (NPS) and would be rushed to the site, but unfortunately, to treat nerve agents and cyanide toxicity, antidotes must be administered within minutes rather than hours. There are also detectors used by the military and available to the civilian sector that can be used to identify specific agents.
Contaminated clothing must be removed and the skin should be rapidly decontaminated; it is best if done within a minute, but this is rarely achieved. Ideally, patients should be decontaminated at the scene before transportation, but this again infrequently occurs. Soap and water are effective decontaminates, and if available a dilute solution of hypochlorite (household bleach) can be used to decontaminate the skin. The military uses 0.5% and most emergency medical teams use 1 to 2% concentration (household bleach is 5%) hypochlorite.
Specific Agents
Nerve Agents. The 5 chemicals in this group are derived from organophosphate compounds first synthesized in Germany in the 1930s that inhibit acetylcholinesterase. They are liquid at room temperature and in vapor form penetrate the cornea, dermis, and respiratory tract. VX, though it has greater toxicity, has lower volatility than any other nerve agent. The antidotes for acetylcholinesterase poisoning include atropine at fairly high doses, on the order of several milligrams to hundreds of milligrams in some cases, and pralidoxime (2-pam), up to 8 mg. Because of the military’s prophylactic use of pyridostigmine, anesthesiologists caring for soldiers in the operating room must be aware of this possibility if one is contemplating using a neuromuscular blocking agent. Neuromuscular blockers should be used with caution, or avoided in patients who may have received pyridostigmine. The effects of these agents are due to unopposed action of acetylcholine at muscarinic and nicotinic receptors. Initial effects are related to the muscarinic effects including rhinorrhea, salvation, miosis, and headache. With severe poisoning, nicotinic effects can be observed. The combination of muscarinic and nicotinic effects are manifested by bronchospasm, vomiting, incontinence, muscle fasciculation, convulsions, respiratory failure, and death.
Pulmonary Agents. Chlorine and phosgene produce pulmonary toxicity. With inhalation, there is destruction of epithelium and endothelium with resultant pulmonary edema, which can lead to hypoxia and death. There are no specific antidotes for phosgene or chlorine. Patients must be removed from further exposure, given supplemental oxygen, and be evaluated and managed as would any other patient in whom you were worried about acute lung injury or ARDS. The need for airway skills and ability to ventilate large numbers of patients would have to be anticipated and emergency response plans implemented.
Blood Agents (Cyanide). Cyanide has toxicity because of binding to hemoglobin with the production of cyanohemoglobin; patients die of tissue hypoxia. The antidote for cyanide is the same as what we would use for patients who had an overdose of sodium nitroprusside, i.e., sodium thiosulfate. Amyl nitrate is more readily available but not as effective.
Skin Agents. Sulfur mustard is an oil at room temperature and will remain in liquid form in a cold environment, but will evaporate in a warm, dry environment. Mustard gas can penetrate ordinary clothing. It is an alkalating agent and, therefore, binds with most biologic molecules. Though mortality is low, the resulting effects on the eyes, skin, and respiratory tract can be quite debilitating. In high dose, it can also have effects on the hematopoetic system leading to leukopenia and anemia. There are no specific antidotes for sulfur mustard other than cleansing the skin. Dimercaprol is a specific antidote to lewisite.
Summary
A plan for dealing with chemical agents should be part of any hospital’s or healthcare provider’s plan to respond to an event or attack in which weapons of mass destruction may be used. One must consider exposure to a chemical agent in any situation where there are multiple casualties without a logical explanation or if patients present with unusual symptoms. If survival is to be improved, the diagnosis must be made and treatment given expeditiously, especially with nerve agent or cyanide poisoning. Healthcare providers must remember to protect themselves, lest they also become a casualty and place further burden on the healthcare system. The preliminary response to a chemical attack involves decontamination at the scene, with removal of clothes, shaving of contaminated hair, and irrigation with soap and water or dilute 0.5 to 2% hypochloride. Antidotes can be given to specific agents if they are suspected or proven. The best response to any such scenario can only be achieved through preparedness.
Dr. Murray’s affiliation and credentials are detailed on Page 3 following his previous Newsletter contribution.
Reading List
- Wetter DC, Daniell WD, Treser CD: Hospital preparedness for victims of chemical or biological terrorism. Am J Pub Health 91:710-716, 2001.
- Evison D, Hinsley D, Rice P: Chemical weapons. Br Med J 324:332-5, 2002.
- Brennan RJ, Waeckerle JF, Sharp T, Lillibridge SR: Chemical warfare agents: emergency medical and emergency public health issues. Ann Emerg Med 32:191-204, 1999.
- Tucker JB: National health and medical services response to incidents of chemical and biological terrorism. JAMA 278:362-368, 1997.