Management of Chemical Casualties The Chemical Incident Management of Chemical Casualties

Hospital Provider Management of Chemical Agent Casualties MODULE 3: HOSPITAL MANAGEMENT OF CHEMICAL CASUALTIES Hospitals represent a vital disaster resource to local communities. After a terrorist attack, victims - either on their own or by emergency vehicles - will go to emergency departments regardless of the level of preparedness of the medical facility. It is essential that hospitals develop an awareness and operational level of understanding regarding the consequences of a terrorist attack. This module of instruction should enable students to describe types of chemical warfare agents, recognize signs and symptoms of exposure, and describe how to manage the victims of a chemical agent attack. NOTE: Greet the class and introduce yourself. Describe a few basic concepts to be covered in this module (such as the nature of chemical agents and hazards they present). Your knowledge base can be increased by referring to the references for this module prior to lecturing.

Chemical Warfare Agents Terminal Objective Describe types of chemical warfare agents Recognize signs and symptoms of exposure Describe management of chemical agent attack victims Upon completion of this module of instruction, students will be able to accomplish these three components of the terminal learning objective. NOTE: Do not dwell on background information or industrial chemicals. Blister and nerve agents should be the main focus of this presentation.

Chemical Warfare Agents Historical Perspective Chemicals used in military operations to kill, injure, or incapacitate Battlefield use World War I and Middle East conflicts Terrorist use Matsumoto and Tokyo, Japan CHEMICAL WARFARE AGENTS - HISTORICAL PERSPECTIVE Chemical warfare agents are hazardous chemicals that have been designed for use by the military to irritate, incapacitate, injure, or kill. Some have local effects on the eyes, skin, or airways (riot control agents, chlorine), and some also have systemic effects (nerve agents and vesicants). Germany first utilized chemical warfare agents during World War I at Ypres, Belgium, in the late afternoon of April 22, 1915. In that attack, the Germans released 168 tons of chlorine. The allies claimed 20,000 casualties and 5,000 deaths. In July 1917, the Germans first used sulfur mustard, again in Ypres. Overall, chemical agents caused large numbers of casualties in WW I, but killed fewer than 5 percent of these casualties, excluding those from Russia (who reportedly may have had insufficient and ineffective protective masks). During World War II, Germany developed several chemical agents, including nerve agents, but did not use them in battle for reasons that are still unclear. After the Second World War, Egypt allegedly used chemicals in Yemen, and Iraq used them against Iran and the Iraqi Kurds. On June 27, 1994, the Aum Shinrikyo, a well-funded Japanese religious cult, initiated the use of chemical warfare agent terrorism in Japan. The nerve agent GB, or sarin, was manufactured in a secret facility in Japan and was first released in Matsumoto, Japan with approximately 280 casualties and 7 deaths. Nine months later, on March 20, 1995, sarin was released in five separate subway cars in downtown Tokyo. There were 12 deaths, hundreds injured (a few dozen seriously), and thousands who sought medical care. Some of the first responders were contaminated, and a few of the hospital staff suffered exposure to the chemical, possibly due to vapor off-gassing from clothing. Some of the responders required admission to hospitals.

Chemical Agent Terrorist Attacks Matsumoto: Approximately 280 injured 7 dead Tokyo 12 dead Approximately 1,000 hospitalized 5,500 sought medical care 10% of first responders injured CHEMICAL AGENT TERRORIST ATTACKS The sarin nerve agent attack in Matsumoto, by the Aum Shinrikyo (June 27, 1994), was a haphazardly planned assassination attempt against three judges who were expected to rule against the Aum in their attempt to purchase real-estate. To prevent this ruling, the sect’s leader, Shako Asahara, ordered a sarin attack on the judges, according to confessions made later by senior Aum officials. Asahara believed that if the judges were killed they could not return a decision against the sect. The Aum converted a 2-ton, white refrigerator truck which contained three tanks to hold the liquid sarin, a heater to vaporize the chemical, and a fan to disperse the agent. The plan was to park the truck right in front of the district courthouse (pictured above) and spray the sarin through the front doors to the rooms inside. This was to occur during broad daylight, potentially exposing large numbers of innocent people to the deadly vapor. The attackers, however, arrived late at the courthouse after the judges had already left for the day. Instead of delaying the attack to the next day, the six-man team decided to release the sarin at the judges’ apartment building later that evening.

Chemical Warfare Agents Nerve Agents Vesicants Industrial Chemicals Riot Control Agents Tabun, Sarin, Soman, VX Mustard, Lewisite Phosgene, Chlorine, Ammonia, Cyanide Mace®, Pepper Spray CHEMICAL WARFARE AGENTS The types of chemical warfare agents listed on this slide are the ones we will focus on during this module. Some of the chemical warfare agents are said to have characteristic odors, such as a horseradish or mustard smell for mustard agent, Lewisite’s aroma of geraniums, or the freshly-mown hay smell of Phosgene. However, these are not adequate warning properties for the purpose of protecting yourself against adverse health effects associated with exposure. NOTE: Students might be interested to know that mustard agent got its name from its mustard or horseradish-like odor. The sense of smell is, in any case, a poor detector for chemical warfare-type agents, because a detectable odor would likely mean that a serious exposure has already occurred. An important point for hospital care providers, however, is that conscious patients may be able to provide agent odor information which might aid in diagnosis and treatment. Information on the common industrial chemical cyanide is provided in the Additional Reading section at the end of this book.

Nerve Agents Tabun (GA), Sarin (GB), Soman (GD), VX Most toxic of the chemical agents Penetrate skin, eyes, lungs Loss of consciousness, seizures, apnea, death after large amount Diagnosis made clinically; confirmed in laboratory (cholinesterase) NERVE AGENTS The nerve agents are tabun (GA), sarin (GB), soman (GD), and VX. Nerve agents are the most toxic of all the weaponized military agents. These agents can cause sudden loss of consciousness, seizures, apnea, and death. GB, or sarin, is one of the more commonly stockpiled nerve agents, and it may be inhaled as a vapor, or cause toxic effects by contact with the skin in the liquid form. VX is mainly a liquid skin hazard at normal ambient temperatures. These chemicals are easily absorbed through the skin, eyes, or lungs. The diagnosis of a nerve agent poisoned casualty must be made clinically. There usually is not time for laboratory confirmation. Nerve agents (and similar substances) inhibit cholinesterase, an enzyme present in tissues and blood; there is a laboratory test to determine its activity in blood. Nerve agents are organophosphates (pesticides) that were developed by the Germans (G-agents) in the 1930s and the British (V-agents) in the 1950s during their research into finding more toxic insecticides. . INSTRUCTOR NOTE: To reinforce the fact that nerve agents, while being a weapon of mass destruction, are nevertheless similar in some ways to common pesticides, students might be asked if they have ever used Malathion, Diazinon, or some other common domestic insecticides. Point out that such common substances which are of organophosphate composition are, in fact, household “nerve agents” for insects.

ACh Normal Nerve Function NORMAL NERVE FUNCTION Nerves communicate with muscles, organs, and other nerves by releasing chemicals or neurotransmitters at their connection site (synapse). One of the most common neurotransmitters is acetylcholine (ACh), which is released and collects at the receptor site stimulating the end organ to respond and produce a variety of effects: muscle contractions, gland secretion, and nerve-to-nerve conduction. ACh NOTE: In this graphic, the receptor target to the right of the synapse could be the continuing nerve, a gland, or a muscle. NOTE: At instructor’s discretion, an optional video describing nerve agent physiological effects may be used.

ACh Normal Nerve Function When a nerve impulse reaches the synapse, ACh is released from the nerve ending and diffuses across the synaptic cleft to combine with receptor sites on the next nerve, and the electrical message continues. NOTE: Emphasize that the effect of unwanted electrical message propagation depends on the receiving end organ. A gland will continue to secrete, a muscle will continue to contract, a nerve will continue to generate additional electrical impulses.

Normal Nerve Function AChE ACh To stop further stimulation of the nerve, ACh is rapidly broken down by acetylcholinesterase (AChE), producing choline, acetic acid, and the regenerated enzyme. Thus, a “check and balance” system prevents the accumulation of ACh and the resultant over-stimulation of nerves, muscles, and glands. ACh NOTE: This slide is an artist’s depiction of AChE metabolism of the neurotransmitter. The actual location of AChE is on the post-synaptic membrane, not in the synaptic cleft. Consider re-emphasizing that inhibition of the AChE allows accumulated ACh to continue stimulating muscle contraction, gland secretion, and nerve propagation of unwanted impulses. This mechanism relates directly to the signs and symptoms resulting from nerve agent exposure, and relating this process of effects to patients with apparently bizarre and varied symptoms could be extremely important in making a correct diagnosis in the aftermath of a terrorist attack.

AChE GB ACh How Nerve Agents Work HOW NERVE AGENTS WORK The term “nerve agents” refers to chemicals that produce biological effects by inhibiting the enzyme AChE, thus allowing the neurotransmitter ACh to accumulate. Included among the “nerve agents” are some drugs (such as physostigmine and pyridostigmine) and some insecticides (Sevin®, malathion, and related insecticides). These compounds cause the same biological effects as the nerve agents developed for military use, but the latter are more than a hundred-fold more potent. As a result of inhibition of AChE, the neurotransmitter ACh accumulates to over-stimulate the organs it normally stimulates in the portion of the nervous system. This causes hyperactivity in these organs. These are all innervated by the cholinergic portion of the nervous system and have muscarinic receptors, nicotinic receptors, or a combination (central nervous system and cardiovascular system). ACh GB

Effects of Nerve Agents Organs with cholinergic receptors Muscarinic Smooth muscles Glands Nicotinic Skeletal muscles Ganglia EFFECTS OF NERVE AGENTS The clinical effects of nerve agents are in organs that have cholinergic receptors. These are divided into muscarinic sites and nicotinic sites. Organs with muscarinic receptors include smooth muscles and exocrine glands (post-ganglionic parasympathetic fibers); those with nicotinic sites are skeletal muscles and pre-ganglionic (sympathetic and parasympathetic) fibers. NOTE: The distinction between muscarinic and nicotinic receptor sites in the body is extremely significant, because atropine, the major antidote to nerve agent poisoning, has its primary effect on organs with muscarinic receptor sites. Atropine is relatively ineffective on organs with nicotinic receptor sites.

Signs and Symptoms of Nerve Agents Muscarinic Sites Increased secretions Saliva Tears Runny nose Secretions in airways Secretions in gastrointestinal tract Sweating NERVE AGENT SIGNS AND SYMPTOMS - MUSCARINIC SITES Over-stimulation at muscarinic sites will increase secretions. The victim may experience increased saliva, tearing, runny nose, phlegm in the airways, sweating, and copious secretions in the respiratory and gastrointestinal tracts.

Signs and Symptoms of Nerve Agents Muscarinic Sites Smooth muscle contraction Eyes: miosis Airways: bronchoconstriction (shortness of breath) Gastrointestinal: hyperactivity (nausea, vomiting, and diarrhea) The accumulated ACh also causes pinpoint pupils (miosis), bronchoconstriction (shortness of breath), and hyperactivity of the gastrointestinal tract (nausea, vomiting, and diarrhea). This man was accidentally exposed to an unknown amount of nerve agent vapor. The series of photographs shows his eyes gradually recovering their ability to dilate. All photographs were taken with an electronic flash (which blinks too quickly for the pupil to react to) after the subject had been sitting in a totally dark room for 2 minutes. These photographs were taken (from top to bottom) at 3, 6, 13, 20, 41, and 62 days after the exposure. NOTE: Pupil size of the above patient at 3 days post-exposure was approximately 2 mm, and at 62 days was approximately 8 mm. This test was developed to identify minute deficiencies in pupil response due to the effects of nerve agent exposure. Under normal indoor lighting conditions, the pupils of a nerve agent casualty might appear normal within approximately 7 days, but testing an exposure victim in complete darkness emphasizes the fact that pupil response does not completely return to normal for many weeks.

Signs and Symptoms of Nerve Agents Nicotinic Sites Skeletal muscles Fasciculations Twitching Weakness Flaccid paralysis Other (ganglionic) Tachycardia Hypertension GB ACh NERVE AGENT SIGNS AND SYMPTOMS - NICOTINIC SITES There are also nicotinic receptors which are stimulated by ACh. Over-stimulation causes skeletal muscle fasciculations, twitching, cramping, weakness, and finally paralysis. There is also stimulation of the pre-ganglionic fibers which may contribute to hypertension and tachycardia. The combination of pinpoint pupils and muscle fasciculations is the most reliable clinical evidence of organophospate (nerve agent) poisoning.

Nerve Agents Other Signs and Symptoms Cardiovascular Tachycardia, bradycardia Heart block, ventricular arrhythmias Central Nervous System Acute Loss of consciousness Seizures Apnea Prolonged (4-6 weeks) Psychological effects OTHER SIGNS AND SYMPTOMS OF NERVE AGENTS Cardiovascular. Bradyarrhythmias, heart block, tachyarrhythmias (sinus tachycardia), and ventricular arrhythmias (ventricular tachycardia and ventricular fibrillation) may occur, but most disappear once the antidote is given. Central nervous system. Acute severe effects include loss of consciousness, seizures, and apnea. Effects from a mild exposure include nervousness, fatigue, minor memory disturbances, irritability, and other minor psychological symptoms. The latter, whether caused by a severe or mild exposure, might linger for 4 to 6 weeks after exposure before resolving. NOTE: An optional sequence from the Chemical Stockpile Emergency Preparedness Project (CSEPP) video showing the effects of ACh and AChE may be shown.

Signs and Symptoms of Nerve Agents Vapor Exposure Mild exposure Miosis (dim vision, eye pain), rhinorrhea, dyspnea Moderate exposure Pronounced dyspnea, nausea, vomiting, diarrhea, weakness Severe exposure Immediate loss of consciousness, seizures, apnea, and flaccid paralysis Vapor effects occur within seconds, peak within minutes; no late onset VAPOR EXPOSURE SIGNS AND SYMPTOMS After a mild exposure to vapor of a volatile nerve agent like GB, the most common effects are miosis (often with pain in the eye or head, complaints of dim or blurred vision, or possibly nausea and vomiting), conjunctival injection, rhinorrhea, and some degree of bronchoconstriction and bronchosecretions (with associated complaints of “a tight chest” or “shortness of breath”). A moderate exposure to the agent may bring on additional systemic symptoms, such as nausea, vomiting and diarrhea. Increased respiratory difficulty would also occur, and the patient could be expected to experience a sensation of general muscle weakness. After a severe exposure to vapor, the casualty will almost immediately lose consciousness, and seizures will begin within 1 to 2 minutes. After several minutes of seizing, apnea and flaccid paralysis will occur. If the exposure has been small and a victim is removed from the area of the exposure, shortness of breath may improve. In this situation, the removal of clothing is often adequate decontamination. Effects begin within a minute or so after vapor exposure and generally do not worsen significantly once the casualty is out of the contamination. Peak effects usually occur within the first 5 minutes following exposure. NOTE: Emphasize that the effects of vapor exposure appear almost immediately. An emergency department patient who has exhibited no effects within 20 minutes after a possible vapor exposure most likely did not suffer a (vapor) exposure.

Signs and Symptoms of Nerve Agents Liquid Exposure Mild exposure (to 18 hours) Localized sweating Fasciculations No miosis Moderate exposure (<LD50) (to 18 hours) Gastrointestinal effects Miosis uncommon Severe exposure (LD50) (<30 minutes) Sudden loss of consciousness Seizures Apnea Flaccid paralysis Death LIQUID EXPOSURE SIGNS AND SYMPTOMS Persistent agents like VX present more of a liquid contact hazard. The onset of effects following exposure can be delayed from 10 minutes to 18 hours after contact with the agent, depending on the dose. A mild exposure could present as small fasciculations and diaphoresis on the skin at the site of the droplet. Moderate exposure effects might be gastrointestinal (GI), including nausea, vomiting, and diarrhea. A droplet the size of a Lethal Dose for 50 percent of the exposed population (LD50) (10 mg for VX as shown on this penny) on the skin could cause severe exposure symptoms, such as sudden loss of consciousness, seizures, flaccid paralysis, and apnea will occur within minutes. NOTE: The droplet on the penny is a simulant used for demonstration purposes, and is not actually VX, which is nearly colorless. One example to help explain the effects of an LD50 of VX would be to explain that if a drop of the size depicted above were put on the skin of 100 people, 50 of those people would die from the agent’s effects, with the remainder suffering lesser signs and symptoms. While this could occur in minutes in some victims, it could take hours in others, because a number of factors effect the rate at which the body absorbs liquid agent. A patient potentially exposed to liquid nerve agent should be kept under medical observation for 18 hours to guard against potentially serious delayed effects.

Diagnosis of Nerve Agent Exposure Symptomatic May be systemic or organ-specific Combination of symptoms is more definitive Situational Multiple casualties with similar symptoms Time or location factors in common DIAGNOSIS OF NERVE AGENT EXPOSURE Diagnosis of casualties exposed to nerve agent will be based primarily on observations of symptoms. Casualties may exhibit indications of exposure to a specific organ system, such as miosis, or may be suffering from systemic effects such as vomiting or seizures. Any combination of nerve agent symptoms without a definite alternative cause should generate a high index of suspicion that organophosphate poisoning has occurred. The combination of pinpoint pupils and muscle fasciculations is the most reliable clinical evidence of organophospate poisoning. Suspicion that the poisoning could be a terrorist attack involving nerve agents (rather than accidental) should be triggered by the occurrence of several or many casualties with similar nerve agent-like symptoms, particularly if the casualties arrive within a short time period, or all developed symptoms while at the same location or event. While chemical agent detection and identification may eventually confirm a suspicion that a nerve agent attack has taken place, the results of chemical monitoring will probably not be available soon enough to be useful in the initial diagnosis of exposed victims.

Nerve Agent Treatment Airway/ventilation Antidotes High resistance Atropine 2-PAMCl Diazepam TREATMENT OF NERVE AGENT EXPOSURE - AIRWAY AND VENTILATION Establishment of a patent airway is essential for the survival of the severely exposed patient. Severely intoxicated patients will die if aggressive airway management is not quickly available. With large numbers of victims, rapid scene and resource assessment will influence triage decisions regarding interventional therapy. Because of the intense bronchoconstriction and secretions associated with nerve agent exposure, effective ventilation may not be initially possible due to high airway resistance (50 to 70 cm H2O). Adequate atropinization will reverse these muscarininc effects; therefore, atropine should be administered before other measures are attempted. Endotracheal intubation, followed by positive pressure ventilation with a bag-valve mask, should be performed as quickly as possible. Periodic suctioning of secretions will help to improve ventilation and air exchange. Patients with seizures and respiratory failure can be saved with immediate and adequate intervention. Antidote administration. Three medications are used to treat the signs and symptoms of nerve agent intoxication: atropine sulfate, pralidoxime chloride, and diazepam. The general indications for use of these antidotes will be presented first, followed by a discussion of their use in the treatment of mild, moderate, or severe nerve agent intoxication. NOTE: It is important to stress that attempts to ventilate the rigid airways of a nerve agent patient before treatment with atropine will be very difficult or totally unsuccessful.

Nerve Agent Treatment Atropine Antagonizes muscarinic effects Dries secretions; relaxes smooth muscles Given IV, IM, ET No effect on pupils No effect on skeletal muscles IV in hypoxic patient Ù ventricular fibrillation TREATMENT - ATROPINE Atropine works to block the effect of the accumulated neurotransmitter, ACh, at muscarinic sites. The more ACh at the sites, the more atropine is required to counteract its effects. Atropine can be administered intravenously (IV), intramuscularly (IM), or endotracheally (ET). Parenteral atropine will reverse the muscarinic effects such as rhinorrhea, salivation, sweating, bronchoconstriction, bronchorrhea, nausea, vomiting, and diarrhea. Atropine will not reverse nicotinic effects such as fasciculations, twitching, or muscle weakness. Nor are miosis or ciliary body spasm reversed by parenteral atropine; relief of intractable pain in or around the eye requires the instilling of 1 percent homatropine or atropine topically. Although the IV route of atropine administration is preferred when treating system effects, this should be avoided in hypoxic nerve agent casualties. Because studies have documented the occurrence of ventricular fibrillation when atropine is administered IV to hypoxic animals, atropine should be administered IM in these patients. NOTE: Atropine is, of course, a common medication in ambulances as well as healthcare facilities. Care should be taken in planning for response to nerve agent exposure, however, because the quantity of atropine needed to treat organophosphate exposure is far in excess of that which is typically used to care for a cardiac patient. Counting on cardiac dosages of the medication to deal with the effects of a nerve agent attack could lead to complete depletion of a hospital’s stock of atropine.

Nerve Agent Treatment Starting dose - 2 mg Maximum cumulative dose - 20 mg Total dose calculated over time; but enough must be administered to abate severe symptoms if casualty is to survive Insecticide poisoning requires much more Side effects in normal people Mydriasis Blurred vision Tachycardia Decreased secretions and sweating The initial parenteral dose of atropine is 2 to 6 mg in the adult, with subsequent doses titrated to the severity of the nerve agent signs and symptoms. Treatment for chemical nerve agent exposure might require up to 10 to 20 mg of atropine, or more if required to abate severe symptoms. Severely symptomatic casualties who receive inadequate atropine will be difficult to ventilate effectively, and will therefore have a poorer prognosis than those treated with sufficient medication to abate the most serious airway symptoms. (In patients poisoned with insecticides, over 2,000 to 3,000 mg of atropine might be necessary.) When atropine therapy exceeds the amount necessary to reverse the effect of the cholinergic hyperstimulation, it may cause toxicity manifested by dry mouth, flushing, and diminished sweating, but this would be extremely unlikely in a patient poisoned by an organophosphate (OP) compound. Side effects in unexposed people (not poisoned by OP compounds) include mydriasis, blurred vision, tachycardia, and diminished secretions. The latter (i.e., loss of sweating) may be of concern in a hot environment.

Nerve Agent Treatment Atropine - How much to give? Until secretions are drying or dry Until ventilation is “easy” If conscious or casualty is comfortable Do not rely on heart rate/pupil size Atropine dosing is guided by the patient’s clinical presentation and should be given until secretions are dry or drying and ventilation becomes less labored. When shortness of breath, increased airway resistance, and secretions have abated and the patient is breathing easier, he or she has received enough atropine. Heart rate and pupillary size, ordinarily accurate reflections of atropine dosing, are not useful for clinical monitoring after nerve agent exposure. NOTE: While nebulized bronchodilators such as albuterol are one standard approach to relieving dyspnea due to bronchoconstriction, these medications will be less effective than atropine when treating a nerve agent casualty. The primary effect of albuterol is on beta-adrenergic receptors, while atropine has the specific anti-cholinergic action necessary to counteract the effects of bronchoconstriction and hypersecretion caused by nerve agent exposure.

Nerve Agent Treatment Pralidoxime Chloride (2PAM-Cl) Nerve Agent Remove nerve agent from AChE in absence of aging 1 gram slowly (20-30 minutes) in IV infusion Hypertension with rapid infusion No effects at muscarinic sites Helps at nicotinic sites AChE 2-PAMCl Nerve Agent TREATMENT - PRALIDOXIME CHLORIDE (2PAMCl) This is an antidote that can specifically break the bond between the nerve agent and the enzyme AChE and remove the agent. This will free the enzyme, making it once again available to break down ACh. Clinically, this will decrease muscle twitching, improve muscle strength, and allow the patient to breathe better; however, it has little effect on the muscarinic effects described previously. The bond between the enzyme and the nerve agent can age, a process by which the enzyme and agent become irreversibly bound. The half time for aging of sarin is 4 to 5 hours; this means that half of the bound sarin-enzyme complex can be reactivated 4-5 hours after sarin exposure by administration of the antidote. For VX exposure, the half time for aging of the VX-enzyme complex is 60 hours. The complete time for aging of sarin is about 10 times the half time (40-50 hours), and at this point the bond becomes permanent. Usually, there is plenty of time to treat patients with 2-PAMCl after exposure to nerve agents with the exception of GD. The soman-enzyme complex ages in about 2 minutes. NOTE: The speed with which Soman ages probably will not be significant from the immediate medical treatment standpoint for two reasons: 1. The exact identity of the chemical agent (Soman vs. other nerve agents) probably will not be immediately known after an attack. 2. The amount of 2-PAMCl used will not harm the patient. Administration of the 2-PAMCl should be by slow IV infusion, over 20 to 30 minutes. Rapid IV infusion will produce hypertension. The oxime can also be given IM, 1 gram in 3.3 ml in divided doses, as in the MARK I autoinjector.

Nerve Agent Treatment - Autoinjectors TREATMENT - AUTOINJECTORS - MARK I KIT Atropine and pralidoxime chloride (2-PAMCl), are used by the military in autoinjectors which together are called the MARK I kit. The atropine autoinjector contains 2 milligrams (mg) of atropine and is administered IM by pressing the end of the device onto the thigh. A spring pushes the needle into the muscle and causes the atropine to be injected. This device causes atropine to be absorbed more rapidly than when administered by a conventional needle and syringe. The other autoinjector contains 600 mg of 2-PAMCl. The Food and Drug Administration (FDA) has approved the autoinjectors, but local protocols will determine their use in the field.

MARK I Injection vs. IM or IV MARK I INJECTION VS. IM OR IV ROUTE Using cardiac response as an indicator of atropine uptake over time, the above chart demonstrates the effectiveness of the MARK I injector at administering the medication. While intravenous atropine predictably has an immediate effect, it is an effect which also begins to diminish rapidly. Standard intramuscular injections of atropine may not cause peak effects for nearly an hour, whereas the autoinjector administration, due to its force of injection, causes peak reaction in half the time noted for a standard IM dose. The MARK I injection effects are also seen to be of comparatively long duration.

Nerve Agent Treatment Diazepam Decreases seizure activity Reduces seizure-induced brain injury Give to severely-intoxicated casualties whether convulsing or not TREATMENT - DIAZEPAM Seizures are treated with benzodiazepines such as diazepam. These medications can be used IV or via an autoinjector which contains 10 mg of diazepam. In an emergency department setting where respiratory status can be closely monitored, higher doses may be necessary; animal data shows that doses which equate to 30 or 40 mg in humans may be required to stop seizures. Some authorities recommend treating all severely exposed patients with diazepam whether they are convulsing or not. If three atropine MARK I kits are required initially because of the victim’s clinical presentation, diazepam should be administered immediately thereafter. Other benzodiazapines commonly used in hospitals may work equally well. It is important for emergency department personnel to be aware that other commonly used anticonvulsants, including phenytoin, valproic acid, phenobarbitol, and carbamazepine, are INEFFECTIVE against nerve agent-induced seizures. The pathophysiology of this state is not the same as commonly encountered status epilepticus. One class of drugs which is not commonly used in status epilepticus but which, based on animal data, is highly effective against nerve agent-induced seizures is the anticholinergic class. Trihexyphenidyl HCI and scopolamine have been shown effective in monkeys in ongoing studies.

Nerve Agent Treatment Treatment regimen No signs/symptoms Reassure Observe Vapor: 1 hour Liquid: Up to 18 hours TREATMENT REGIMEN - LATENT EFFECTS Asymptomatic victims who present to the ED alleging exposure to nerve agents should be considered potentially exposed, triaged for other injuries, and observed for up to 1 hour if a vapor exposure is alleged, or up to 18 hours if a liquid exposure is possible (or if the exposure history is uncertain).

Parenteral atropine will not reverse miosis Nerve Agent Treatment Mild vapor exposure Miosis, rhinorrhea - observation only Increasing SOB - treat Mild liquid exposure Localized fasiculations & sweating - treat One MARK I kit (2 mg atropine/ 600 mg 2 -PAMCl) OR 1 gram 2-PAMCl IV 2 mg atropine, IM or IV Parenteral atropine will not reverse miosis TREATMENT OF MILD VAPOR AND LIQUID EFFECTS Mild vapor effects: The presence of miosis and rhinorrhea requires observation only. If the victim is suffering from airway effects (shortness of breath, chest tightness, and profuse airway secretions) that are not improving, then treat with 2 mg of atropine IM or IV, or with the MARK I kit. If they are comfortable although slightly short of breath, give nothing and observe. Supplemental oxygenation will be needed only in those patients with pulmonary or cardiac disease. IM atropine dosing can be repeated at 5 to 10 minute intervals as needed. [Note: Patients with pinpoint pupils may have severe light sensitivity and pain, but only require reassurance since these symptoms will resolve. At the hospital, these patients should be given a topical atropine or homatropine only for relief of severe pain in the eye(s) or head because the drug causes blurred vision. This may be done if miosis occurs as part of moderate or severe systemic effects as well.] Mild liquid effects: If there are mild effects from liquid exposure (localized sweating and fasciculations at the site of liquid contact), give 2 mg of atropine and 600 mg 2-PAMCl IM (MARK I kit) or 1 gram (gm) 2-PAMCl IV slowly over 20 to 30 minutes. NOTE: After the 1995 Tokyo subway nerve agent attack, 95 percent of symptomatic casualties suffered only from miosis.

Moderate vapor or liquid exposure Nerve Agent Treatment Moderate vapor or liquid exposure One or two MARK I kits Or give IV: 2 to 4 mg atropine 1gm 2-PAMCl (infusion) TREATMENT OF MODERATE VAPOR AND LIQUID EXPOSURE Moderate Vapor Exposure: Be more aggressive with moderate vapor exposures. Symptoms will include those for mild exposures with more severe respiratory distress and may be accompanied by muscular weakness and possibly GI effects (vomiting and diarrhea). Initial dose for these patients is 1 or 2 MARK I kits containing a total of 2 mg atropine and 600 mg 2-PAMCl. Treatment may also be given IV, with 2 to 4 mg atropine given IV push, and 1 gram of 2-PAMCl given by IV infusion slowly. This dosing can be followed by repeat doses of 2 mg of atropine at 5 to 10 minute intervals as needed, and 600 mg of 2-PAMCl for a total of 1,800 mg 2-PAMCl with the MARK I kit IM (or 1 gm 2-PAMCl IV over 20 to 30 minutes for a total of three doses at hourly intervals). Moderate Liquid Exposure: For moderate toxicity several hours after liquid exposure, 2 mg of atropine and 600 mg 2-PAMCl should be given initially. Repeated doses of atropine and 2-PAMCl may also be necessary. Oxygen may be needed in those with cardiac or pulmonary disease who have severe breathing difficulty, but generally, it is not necessary.

Severe - vapor or liquid Nerve Agent Treatment Severe - vapor or liquid Give 3 MARK I kits or 6 mg atropine and 1 gram of 2-PAMCl as soon as possible Airway Ventilation/O2 Consider diazepam 10 mg IM (2 to 5 mg IV) Repeat atropine every 5 to10 minutes as needed Repeat 2-PAMCl in one hour TREATMENT OF SEVERE EXPOSURE The severe vapor-exposed casualty will be unconscious, possibly seizing or post-ictal, twitching or flaccid, possibly apneic or with severe dyspnea. There may be effects in two or more body systems (dyspnea, vomiting/diarrhea, severe twitching, loss of consciousness). These casualties should be given 6 mg or atropine IM immediately, and 2-PAMCl should be started. Alternatively, 3 MARK I kits should be given as quickly as possible, with diazapam considered. These patients will require assisted ventilation with oxygen. NOTE: It should be emphasized that antidote administration must be the top priority in treating a severely exposed nerve agent casualty. Maintaining the airway and providing ventilatory support will be vital, but these measures are unlikely to be effective if atropine has not been administered. Airway constriction and hypersecretion can require positive pressure ventilation at 70 cm/H20 or higher pressures prior to treatment with atropine. This is particularly significant in light of the fact that some bag valve mask ventilators have pressure relief valves preset to 45 cm/H20.

Nerve Agent Age-Related Treatment Atropine Infant (0 to 2) 0.5 mg IM IV for infants and children 0.02 mg/kg Child (2 to 10) 1.0 mg IM Adolescent (> 10) 2.0 mg Elderly 1.0 mg IM SPECIAL AGE-RELATED ANTIDOTE DOSING CONSIDERATIONS Atropine: Certain members of the population may be more sensitive to atropine. These include infants, young children, and the elderly. Pediatric experts have divided the age groups for IM administration of atropine. These doses may be repeated as clinically indicated. If atropine is to be given IV, then the dose is 0.02 mg/kilogram (kg) for infants up through young adults. If only standard MARK I kits are available, the use of a 2 mg atropine autoinjector can be used, but infants and small children are at risk of being injured by the autoinjector needle. The most significant adverse effect of high dose atropine in the younger patient is the inhibition of sweating. Elderly: In the frail or medically compromised adult, use a 1 mg dose and repeat as necessary. Category Infant Child Adolescent Dose 0.5 mg single dose 1.0 mg single dose 2.0 mg single dose Age 0 to 2 years 2 to 10 years Young adult NOTE: Advise students that the proper antidote dose varies with age group, and that the dosing information is included in their course materials. This will prevent expending an extended period of time covering information they can refer to directly later.

Nerve Agent Age-Related Treatment 2-PAMCl < 20 kg 15 mg/kg IV > 20 kg 600-mg IM autoinjector Elderly 1/2 adult dose (7.5 mg/kg IV) 2 PAMCl-induced hypertension Phentolamine Adult 5 mg IV Child 1 mg IV Pralidoxime chloride: No data are available for 2-PAMCl use in nerve agent exposed children. The standard IV dose for a patient from an infant to a 70-kg person is 15 mg/kg, with the dose repeated twice at hourly intervals. Above 70 kg, the dose should be a total of 1 gm, repeated twice at hourly intervals as necessary. For IM use, the doses should be : These may be adjusted according to subsequent clinical presentation. Elderly: If frail, hypertensive, or with renal disease, use one-half the usual adult dose of 2-PAMCl (7.5 mg/kg IV). If hypertension becomes significant during the administration of the 2-PAMCl, treat with IV phentolamine as follows: Adult: 5 mg IV Child: 1 mg IV Weight < 20 kg > 20 kg Dose 15 mg/kg 600 mg autoinjector NOTE: Advise students that the proper antidote dose varies with age group, and that the dosing information is included in their course materials.

Nerve Agent Age-Related Treatment Diazepam - Infants > 30 days old 0.2 - 0.5 mg/kg IV to 5 years q 2 to 5 min (max 5 mg) - Children > 5 years 1 mg IV q 2 to 5 min (max 10 mg) Diazepam: Recommended pediatric doses: Infants > 30 days to age 5 0.2 to 0.5 mg/kg IV slowly every 2 to 5 minutes to maximum dose of 5 mg 1 mg IV every 2 to 5 minutes to maximum dose of 10 mg Children > 5 years NOTE: Advise students that the proper antidote dose varies with age group, and that the dosing information is included in their course materials.

Nerve Agent Summary Vapor exposure Liquid exposure Symptoms develop suddenly Most ambulatory victims require minimal intervention Risk of secondary contamination, which is minimized by removing the victim’s clothing Requires immediate access to antidotes Liquid exposure Symptoms delayed minutes to hours Greater need for decontamination High risk of secondary contamination; victims require decontamination (clothing removal & washdown) Requires immediate access to antidotes NERVE AGENT SUMMARY Volatile nerve agents, such as sarin, are non-persistent chemicals that pose primarily an inhalation hazard. Symptoms of exposure develop within seconds, but tend not to worsen if the victim is able to be evacuated from the area. Those individuals who either inhale a toxic dose or are unable to be evacuated from the release site, will experience the highest mortality rates. Those individuals who are able to leave the release area quickly or who are exposed to low levels of the agent will experience the least amount of symptoms and will require minimal medical intervention (the “walking wounded”). Since these agents are highly volatile, first responders and medical personnel are at risk of becoming secondarily contaminated from agent off-gassing. This occurs if the victim’s clothing is not properly handled and responders fail to wear appropriate respiratory protection. Symptomatic individuals require immediate treatment, including airway management and antidote therapy. Nerve agents such as VX are very persistent agents, do not readily vaporize, and pose primarily a liquid threat. The symptoms from such a contamination may be delayed for minutes to hours depending on the concentration, dose, and location of the contaminant on the skin (absorption occurs more readily on moist areas of the skin). Symptoms may even develop slowly in cases where liquid exposure is high. Because victims of a VX attack are contaminated with a liquid, decontamination takes on a higher priority to limit the amount of agent absorption and to minimize the risk of spreading the contamination. Decontamination should ideally be provided simultaneously with antidote administration and airway management, when necessary.

Vesicants (Blister Agents) Sulfur mustard Lewisite BLISTER AGENTS OR VESICANTS Chemical warfare vesicants include sulfur mustard and Lewisite. A close relative of sulfur mustard, nitrogen mustard, was the first cancer chemotherapeutic agent.

Mustard Properties Vapor & liquid threat Latent period between exposure & effects Systemically toxic - similar to radiation MUSTARD - PROPERTIES Sulfur mustard is both a vapor inhalation and liquid contact hazard. Mustard causes injury to the eyes, skin, airways, and some internal organs. This chemical warfare agent has a delayed action, and exposure to it may result in blisters on the skin, temporary blindness, and respiratory distress. More extensive injury can result in death because of respiratory failure from airways injury, or sepsis as a result of bone marrow damage, decrease in white blood cells, and an impaired immune system. There is no specific therapy beyond supportive care. Mustard is absorbed and causes chemical cellular damage within 1 to 2 minutes, but clinical effects do not begin for hours. There is no immediate pain, skin discoloration, or eye irritation after exposure. Hours later, the casualty may recognize that he or she has been exposed and presents to the ED for evaluation and treatment. The onset time for clinical effects ranges from 2 to 48 hours; most commonly is between 4 and 8 hours. NOTE: Emphasize that clinical effects do not occur immediately after exposure. Many patients exposed to mustard might report to the hospital immediately after an incident, but will have no clinical effect, though they could be contaminated and should undergo decontamination. If discharged, these patients may return hours later with erythema and blisters, or eye or airways effects. Although there will be no injury initially apparent, cell changes will have already begun in mustard exposed casualties.

Mustard Effects Quickly cyclizes in tissue Alkylates cell components, including DNA DNA damage, cell death MUSTARD EFFECTS Despite years of research, the exact mechanism by which mustard damages cells is unknown. It alkylates DNA and clings to proteins and other cellular components. The end result is DNA damage and cellular death. The injury is very similar to that produced by radiation, and mustard is a radiomimetic agent. As mentioned earlier, the three organ systems directly affected topically by mustard are the eyes, skin, and respiratory tract. NOTE: As an example of the effects of mustard exposure, the above photo is an injury that occurred when liquid mustard seeped through a grommet on the boot of a chemical weapons destruction plant worker. The worker experienced erythema on the back of his lower leg about 8 hours after exposure. Within 18 to 20 hours, the above blister had appeared. Laboratory testing confirmed his exposure to mustard.

Mustard Effects Eye Injury Mild conjunctivitis Moderate/severe conjunctivitis, lid inflammation and edema, blepharospasm, and corneal roughening Corneal opacification, ulceration, and/or perforation Well over 95% had only mild to moderate conjunctivitis Under 1% had permanent damage to cornea MUSTARD EFFECTS - EYE INJURY There is a spectrum of eye involvement. The eye lesion, after a small exposure to mustard, may consist only of mild conjunctivitis. A larger exposure will produce a more severe conjunctivitis, lid inflammation and edema, blepharospasm, and corneal roughening. These casualties will be unable to open their eyes and will be temporarily without sight. A larger exposure, particularly if by liquid, may produce corneal opacification, corneal ulceration, or corneal perforation. Even with the potential for serious eye damage, the documentation for World War I mustard victims indicates that over 95 percent of those suffering eye injuries from the agent developed only mild to moderate conjunctivitis, and that less than one percent experienced permanent corneal injury. Miosis is sometimes observed after mustard exposure and is thought to be due to cholinergic effects.

Mustard Effects Eye Injury This Iranian casualty has severe keratoconjunctivitis with corneal edema, lid edema, and pus at the corner of the eyes. NOTE: This is the eye of a victim from the Iran/Iraq war, 7 days after exposure to mustard. Using a pointer, emphasize the lid edema, the finger holding the eye open (suggesting blepharospasm which could render a victim functionally blind), conjunctival injection, subconjunctival hemorrhage, and corneal roughening. The yellowish exudate could be pus, but is more likely the residue of medication previously introduced into the eye.

Mustard Effects Skin Injury Erythema Small vesicles; later coalesce Blisters/bulla Possible coagulation necrosis with liquid MUSTARD EFFECTS - SKIN INJURY These begin hours after exposure with erythema as shown in this Iranian casualty (accompanied by burning and itching), followed later by the development of small vesicles; later, these small vesicles coalesce to form blisters. The size and depth of the lesion depends on the amount of exposure and whether exposure was by vapor or liquid. Coagulation necrosis extending into the dermis may develop under blisters caused by liquid, such as those blisters shown on this photograph of a worker’s hand several days after he was accidentally exposed to liquid mustard. NOTE: The erythema evident on the Iranian mustard victim shown above probably developed within 24 hours of the time of his exposure; the photo was taken 5 days after exposure. In addition to skin damage, this patient also suffered pulmonary injury (note the oxygen cannula.)

Mustard Effects Airway Injury Upper: nose sinuses, pharynx (epistaxis, sore throat, hacking cough) Mid: Larynx (hoarseness) Lower: Bronchioles (dyspnea, productive cough) Pulmonary edema is rare MUSTARD EFFECTS - AIRWAY INJURY Mustard damages the mucosa or lining of the airways. This damage begins in the upper airways and descends in a dose-dependent manner to the smallest bronchiole. After a small exposure or initially after a large exposure, there may be epistaxis, sinus discomfort, and a mild to moderate pharyngitis with a hacking cough. After a moderate exposure, or later after a large exposure, there may be laryngitis with voice loss and a productive cough. If the exposure is large, the agent reaches the smallest airways to cause dyspnea and productive cough, as the mustard will damage not only the mucosa, but the underlying musculature as well. At this stage, there may be hemorrhagic pulmonary edema around the bronchioles, as depicted above, but otherwise, pulmonary edema is rare. NOTE: The above photo depicts a cross-section from the lung of a mustard vapor victim. Using a pointer, emphasize the absence of mucosa, the absence of a muscular layer, the necrotic, inflammatory debris in the lumen, the slight hemorrhage around the bronchiole, and the relatively clear alveoli.

Mustard Effects GI Injury Gastrointestinal Within 24 hours Nausea and vomiting Cholinergic effects After 3 to 5 days Tissue destruction MUSTARD EFFECTS - GASTROINTESTINAL INJURY Gastrointestinal effects within the first 24 hours following exposure include nausea and vomiting. These effects are thought to be in part due to cholinergic stimulation. There may be some added effects of mustard on the GI tract from the swallowed tracheal secretions. The initial GI effects effects are are transient, and clear within 24 hours. Gastrointestinal effects seen after 3 to 5 days are thought to be due to tissue destruction in the abdomen, and fluid and electrolyte loss.

Mustard Effects Bone Marrow Damage Damages stem cells Decreased WBC, RBC, platelets after 3 - 5 days Survival rare if WBC < 200 MUSTARD EFFECTS - BONE MARROW DAMAGE Absorption of significant amounts of mustard produces damage to and death of the stem or precursor cells of the bone marrow. If this occurs, the white blood cell count, after an initial increase because of the toxic exposure, starts decreasing on about the third or fourth day after exposure and continues downward until recovery begins. If the amount of mustard absorbed is sufficient to cause leukopenia with a white cell count below 200 cells/mm3, the prognosis is poor; the white blood count may in fact reach zero. Following the white blood cell decrease, the red blood cells and platelets also decline. The relative deficiency of these cells increases susceptibility to infection and contributes to death.

Skin Treatment Decontamination must be done within minutes to reduce damage Delays in decontamination will not prevent illness, but will prevent cross-contamination Supportive care - soothing lotions, frequent irrigation, topical antibiotics, pain medication Do NOT overhydrate; not a thermal burn SKIN TREATMENT Treatment is largely supportive since there is no antidote for the effects of sulfur mustard. Decontamination should consist of physical removal of any residual agent by whatever means available. The casualties should remove all clothing, rings, and jewelry. Limited animal studies have shown that the use of 0.5 percent hypochlorite solutions (bleach) in decontaminating unbraided skin exposed to liquid sulfur mustard may substantially reduce the size of the erythematous lesions, if performed within the first five minutes following exposure. In all other circumstances, the use of copious amounts of water (or soap and water) to flush contaminated skin is probably the best, most expedient method of decontaminating casualties. Wound decontamination should always be performed with sterile water or sterile saline, not hypochlorite solutions. Decontamination must be done as quickly as possible since cellular damage occurs in less than 1 minute. Decontamination of the casualty at the ED 30 minutes or more after contact with mustard will not change the clinical course of the patient’s illness, but is effective in preventing cross-contamination of providers.

Eye Treatment Topical mydriatics Topical antibiotics Vaseline on lid edges Topical steroids (only in the first 24 hrs) EYE TREATMENT A discussion of the therapy for ocular exposures is best begun by repeating the observation that mustard fixes to tissues within the first several minutes after exposure. Gentle irrigation with saline or water during this time period will be helpful. Aggressive attempts to pry apart severely painful, blepharospastic eyelids to accomplish an irrigation 30 minutes or more after exposure is of dubious value, since the damage has been done and the agent has evaporated or has been absorbed. With severe eye injuries, homatropine or other mydriatics should be applied topically to prevent synechiae formation. Topical analgesics may be used for initial examination. However, oral pain medication is preferred to topical analgesics, which may allow damage to the cornea and delay healing. Topical antibiotics should be applied several times a day and petroleum jelly should be applied to lid edges to prevent them from adhering. Many ophthalmologists feel that the application of topical steroids within the first 24 hours, but not after, might be of benefit. Early involvement of an ophthalmologist is advised, and a visual acuity should be obtained before treatment measures are instituted.

Airway Treatment Cool mist, cough suppressants for mild symptoms Oxygen Assisted ventilation Early intubation Bronchodilators (steroids) Antibiotics AFTER organism identified AIRWAY TREATMENT Upper or minor airway symptoms (sore throat, non-productive cough, hoarseness) may be relieved by cool mist inhalation and cough suppressants. The initial chemical pneumonitis should be treated in the usual manner; however, antibiotics should not be used until an organism is demonstrated, which usually occurs between the third and fifth day post-exposure. A patient with severe airway effects will benefit from oxygen and assisted ventilation, particularly positive end expiratory pressure (PEEP) or continuous positive airway pressure (CPAP). Intubation should be performed if there are signs of impending laryngeal involvement, and it should be done early before laryngeal spasm or edema makes it difficult. Bronchodilators may be needed; if they fail to relieve bronchospasm, steroids may be tried. Steroids, however, are of questionable benefit otherwise.

Lewisite Effects Causes severe irritation to eyes, skin, and airways IMMEDIATELY on exposure (no delay) Tissue necrosis, pseudomembranes Increased capillary permeability No bone marrow effects LEWISITE EFFECTS Lewisite is a vesicant that has been stockpiled militarily, but there have been few human exposures to the chemical. Lewisite is rapidly absorbed by the eyes, skin, and lungs and produces blisters similar to sulfur mustard. In contrast to sulfur mustard, however, Lewisite is highly irritating on initial exposure. It also produces visible lesions more quickly. Lewisite causes greater skin damage than sulfur mustard. A gray area of dead skin can progress to blisters and severe tissue necrosis and sloughing. Since it causes immediate irritation to the nose and sinuses, any effort by the victim to evacuate the area of contamination may prevent more severe lung damage. Pseudomembrane formation is common. Lewisite also causes increased capillary permeability, leading to volume depletion and hepatic and renal injury. Unlike mustard, it does not damage the bone marrow. NOTE: Lewisite, named for its inventor, Captain W. Lee Lewis of the U.S. Army Chemical Warfare Service, was produced in 1918 for use in World War I, but didn’t make it to the front before armistice was declared. A stockpile of it destined for Europe was enroute by ship when the war ended. The Japanese mixed Lewisite with mustard for use in bombs and artillery shells which were probably used to attack China starting in about 1935, and the Soviets also stockpiled this agent.

Lewisite - Treatment Immediate decontamination British anti-Lewisite (BAL) for systemic effects Supportive Care Oxygen LEWISITE TREATMENT Decontamination with soap and water will remove most of the chemical if it is performed quickly after contamination. An antidote is available, called British anti-Lewisite (dimercaprol or BAL), which can be used IM to reduce the systemic effects of the vesicant, such as increased capillary permeability with subsequent hypotension and hemoconcentration (which can adversely effect renal function.) As it is administered parenterally, BAL has no effect on Lewisite damage to the skin and eyes. NOTE: Lewisite exposure will necessitate skin decontamination at the earliest possible opportunity because patients will probably be highly symptomatic. Unlike mustard exposure victims, casualties contaminated with Lewisite will suffer immediate and possibly severe skin irritation; prompt decontamination will not only minimize injury, but will increase patient comfort. NOTE: Under emergency circumstances, dilute bleach, soap and water, or copious water are all acceptable decontaminants. The most important factor for Lewisite treatment initially is decontaminating patients as soon as possible with whatever decontamination solution is available.

Vesicant Agent Summary Agents damage eyes, skin, respiratory system; cause additional systemic effects Mustard Fast acting; symptoms delayed, no specific antidote Lewisite Fast acting, symptoms immediate, BAL antidote available Decontamination is best initial treatment VESICANT AGENT SUMMARY Mustard and Lewisite both cause damage within a short period of contacting a victim, though mustard’s symptoms may be delayed many hours while Lewisite causes immediate skin irritation. Both agents can cause injury in their vapor or liquid state by contacting human tissue; the eyes, skin, and respiratory systems are susceptible to damage from their effects. In addition, mustard can cause systemic damage in the form of neurological, gastrointestinal, bone marrow, and blood-forming system effects. The system effects of Lewisite exposure include injury to circulatory system capillaries, allowing fluid imbalances which can lead to liver and kidney damage. Dimercaprol (BAL) can be used to treat Lewisite exposure; treatment for mustard is supportive and generally includes no specific antidote medication. The best initial treatment for persons exposed to either agent is prompt and thorough decontamination. This will also protect healthcare providers from secondary contamination.

Phosgene At high concentrations: Cl Toxic to lungs by inhalation Irritates eyes, nose, upper airways; possible laryngospasm Toxic to lungs by inhalation Carbonyl group damages alveolar-capillary membrane Non-cardiac pulmonary edema: onset 2 to 12 hours Dyspnea, cough with sputum Management of non-cardiac pulmonary edema Hypoxia, fluid loss; requires pulmonary care, careful fluid replacement ABSOLUTE REST POST-EXPOSURE Cl C = O INDUSTRIAL CHEMICALS - PHOSGENE Phosgene has the odor of newly mown hay and becomes a gas at 47 degrees F. It damages primarily the lungs, and must be inhaled to cause this damage. At high concentrations, the chlorine part of the molecule irritates the eyes, nose, and upper airways, and may cause fatal laryngospasm. The real damage is done by the carbon, double-bond oxygen group (carbonyl group) of the phosgene molecule; this causes severe, though not immediately apparent, lung injury. Phosgene is a common industrial chemical, and was also formerly used as a warfare agent. After phosgene is inhaled, the carbonyl group combines with the components of the membrane dividing the alveolus from the capillary, and fluid from the blood leaks first into the alveolar septi and then into the alveoli themselves. Symptoms appear usually from 2 to 12 hours after exposure; the earlier the onset of symptoms, the more severe the effects will be. Dyspnea at exertion worsens to dyspnea at rest after a severe exposure. This is accompanied by a cough productive of frothy, clear sputum. The fluid loss after a severe exposure may be as great as 1 to 2 liters per hour. There are two major components to the physical effects of phosgene exposure: hypoxia because of the fluid-filled alveoli, and fluid loss leading to hypovolemia and hypotension. Management of this non-cardiac pulmonary edema consists of early intubation if the onset of illness is early; ventilation, oxygen, and positive end expiratory pressure (PEEP); bronchodilators if there is evidence of bronchospasm; and antibiotics after a bacterial pheumonia occurs and an organism can be identified. (Steroids may be needed if the usual bronchodilators are not helpful; steroids are not otherwise useful in treating exposures.)

Chlorine High concentration or prolonged exposure Pulmonary edema, sudden death Eye irritation, cough, dyspnea More severe airway and lung damage with high concentration Management Remove from exposure; manage airway Oxygen, ventilation, PEEP Intubation, bronchodilators CHLORINE Chlorine was the first chemical used on a large scale in modern warfare; it was used in 1915 in World War I. Most people are familiar with chlorine and its odor because it is used as a disinfectant in swimming pools. It is commonly stored at water treatment plants, and is also widely used in industry; large amounts are shipped by rail and on roadways. During the 1996 Atlanta Olympics, railroad tank cars of it moved past Olympic Village every day. Chlorine causes irritation to the eyes both as a gas and in solution in swimming pool water. If chlorine gas is inhaled, it causes airway irritation with cough, and a feeling of shortness of breath. Chlorine injures cells by reacting with water to produce hydrochloric acid and oxygen free radicals. It is toxic to any body surface, including the eyes, skin, and respiratory and gastrointestinal tracts. A high concentration will cause more severe pulmonary damage with both airway and parenchymal damage. Sudden death can result from severe hypoxia and cardiac arrest. After an exposure to a high concentration or a prolonged exposure, chlorine can cause non-cardiac pulmonary edema. Intubation should be performed before laryngospasm occurs; oxygen, cool mist, assisted ventilation, the use of PEEP, and bronchodilators may be needed. Fluid replacement may be necessary. Toxicity to the eyes and skin should be treated with copious flushing with water. NOTE: A show of hands regarding how many students in the class have smelled chlorine or suffered effects from it such as eye irritation may emphasize what a common industrial chemical it is.

Ammonia Anhydrous Ammonia Management pH>12; (household ammonia pH < 12) Wide industrial use Plastics, fertilizer, explosives Irritating, corrosive; causes necrosis, severe pain Serious injury to eyes, lungs, skin, GI tract Management Remove from exposure, decontaminate Symptomatic; maintain airway AMMONIA Anhydrous ammonia is not a military chemical agent, but is included because it is very damaging to human tissue and is widely available. Anhydrous ammonia is not to be confused with the household cleaning chemical; anhydrous has a very alkaline pH and is much more toxic. It has a pungent odor. It irritates human tissues, and acts as a corrosive material causing necrosis of tissues. A very small anhydrous ammonia exposure in the eyes will cause burning and tearing; a large exposure can cause severe corneal damage. Both cause severe pain. Airway effects include shortness of breath, coughing, and irritation. A severe exposure will produce a chemical pneumonia with hemorrhage. Ammonia acts like a corrosive on the skin, with pain, erythema, blisters and tissue necrosis. If ingested, it severely damages the gastrointestinal tract. Other than to remove the patient from the exposure and provide thorough decontamination (including copious eye wash), there is no specific management. The airways should receive careful attention.

Riot Control Agents Irritating agents, lacrimators, “tear gas” Cause reaction in Eyes: burning, tearing, eyelid spasm, redness Airways: burning, coughing, dyspnea Skin: burning, erythema Eye irrigation and supportive care RIOT CONTROL AGENTS Most people are familiar with riot control agents or “tear gas.” These agents are used by the military for training, and by law enforcement agencies to subdue crowds or individuals. Mace is sold for individual protection in small spray devices. Pepper spray, derived from the capsicum family of peppers, is relatively new, and is used by the military, law enforcement, and for personal protection. These agents produce eye, nose, mouth, skin, and respiratory tract irritation. This class of chemical agents causes involuntary eye closing due to irritation. For police, this is an effective weapon as it can disable an assailant. The deleterious effect is usually transient (about 30 minutes after exposure). Medical treatment for those exposed to riot control agents will have to deal with their effects on the eyes, respiratory tract, and skin. Eyes should be irrigated copiously with water or saline. Remove contact lenses. Utilize slit lamp exam to make certain that all solid particle foreign bodies are removed. Follow-up with an ophthalmologist is recommended. Treat wheezing with bronchodilators or steroids if standard bronchodilators fail. Provide oxygen therapy if indicated. Most symptoms should be maximal within 1 to 2 hours. Most skin exposures require little more than reassurance. With prolonged pain, decontaminate with soap and water or a solution containing a carbonate and/or a bicarbonate. Do NOT use bleach. Delayed onset dermatitis should be managed with frequent irrigation and soothing ointments or creams. NOTE: Though the signs and symptoms related to riot control agents are generally temporary, exposure to high levels of the chemicals can result in more serious illness. This is especially true in the elderly, children, and individuals with underlying pulmonary disease such as asthma and COPD.

Chemical Agent Summary Vapor exposure Nerve agent symptoms develop suddenly, mustard and phosgene symptoms are delayed Most ambulatory victims require minimal intervention Risk of secondary contamination Requires airway management; antidotes for nerve agents and Lewisite CHEMICAL AGENT SUMMARY Volatile nerve agents (such as sarin) are non-persistent chemicals that pose primarily an inhalation hazard. Their symptoms of exposure develop within seconds, but tend not to worsen if the victim is able to be evacuated into a fresh air environment.. Those individuals who either inhale a toxic dose, are unable to be evacuated from the release site, or have underlying lung disease, will experience the highest morbidity and mortality rates. Victims who are able to leave the release area quickly or who are exposed to low levels of the agent will typically experience the least amount of symptoms and will require minimal medical intervention (the “walking wounded”). Since these agents are highly volatile, first responders and medical personnel are at risk of becoming secondarily exposed from agent off-gassing. This occurs if the victim’s clothing is not properly handled and responders fail to wear appropriate respiratory protection. Symptomatic individuals require immediate treatment, including airway management and antidote therapy. In contrast to the nerve agents, symptoms of phosgene and mustard vapor exposure do NOT develop rapidly. Victims of vapor exposure to these agents will have no symptoms at the time of exposure, but will have serious ones later on. While there is no antidote for mustard exposure, BAL can be used in treatment of Lewisite exposure.

Chemical Agent Summary Liquid exposure Symptoms delayed minutes to hours Greater need for decontamination Risk of secondary contamination, victims require clothing removal & decontamination Requires immediate access to antidotes VX and blistering agents are persistent chemicals that do not readily vaporize, and pose primarily a liquid threat. The symptoms from such a contamination may be delayed for several minutes to hours depending on the concentration, dose, and location of the contaminant on the skin (absorption occurs more readily on moist areas of the skin). Because victims of these types of attacks are contaminated with a liquid, decontamination takes on a higher priority to limit the amount of agent absorption and to minimize the risk of spreading the contamination. Decontamination should ideally be provided simultaneously with antidote administration and airway management, when necessary.