# Presentation: 161415

## MANAGEMENT OF CHEMICAL CASUALTIES

- csepp multi-hazard
- medical curriculum

## Objectives

- List three symptoms of a nerve agent exposure
- State three chemical agents that would require decontamination to treat the exposure

## Chemical Incidents

- Local Communities must prepare:
- Develop regional response plans, protocols and resources
- Develop protective systems
- Training is required:
- Awareness and operational understanding
- Policies and procedures for assessment and treatment

**Notes:**
Although many communities in the U.S. have Hazardous Materials Response Teams (HMRTs), these teams have not been universally trained and their equipment has not been standardized.  Many teams may not be readily available to perform search and rescue after a terrorist attack.  Also, it may be difficult initially for first responders to recognize that injuries are due to a chemical release.  Thus, first responders (police, fire, EMS) and hospital providers may become secondary victims.
Chemical cross-contamination of ambulances and hospitals due to a lack of preparedness, PPE, and decontamination capability could cripple the capacity of the local pre-hospital and hospital system.  One patient exposed to a hazardous chemical can contaminate a transport vehicle and temporarily close a hospital emergency department (ED).  Hospitals and EMS providers have recently received funding (2002) and equipment through the HRSA and CDC grants program. Few hospitals are able to sustain a prolonged decontamination effort.  For communities to be prepared, law enforcement, fire, EMS, and hospital personnel must develop policies and procedures to address:
The safe identification, decontamination, treatment, and transport of the chemically contaminated victim. 
The procurement of adequate caches of antidotes that are readily available to quickly and accurately treat the victims of a chemical agent attack.
The purchase of appropriate PPE and decontamination equipment, with frequent training utilizing this gear to protect the safety of the first responder and hospital caregiver.

## Chemical Warfare Agents

- Chemical Agents
- Chemicals used in military operations to kill, injure or incapacitate
- Local and/or Systemic Effects

**IMAGE:  DOD**

**Notes:**
Chemical warfare agents are hazardous chemicals that have been designed for use by the military to irritate, incapacitate, injure, and or kill.  Some have local effects on the eyes, skin, or airways (chlorine), some have only systemic effects (hydrogen cyanide), and some have both (nerve agents and vesicants).

## Chemical Agents

- Nerve Agents				Tabun, Sarin, Soman, VX
- Cyanide					Hydrogen Cyanide,Cyanogen 							Chloride
- Pulmonary Intoxicants		Phosgene, Chlorine
- Miscellaneous	          		Ammonia
- Vesicants					Mustard, Lewisite
- Riot Control				Mace ®, Pepper Spray, 									Oleoresin Capsicum (OC)

**Notes:**
The types of chemical warfare agents listed on this slide are the ones we will focus on during this module.

## The Senses - Smell

- Sulfur Mustard
- Garlic
- Horseradish
- Phosgene
- Freshly mown hay
- Cyanide
- Bitter almonds
- Lewisite
- Geraniums

**IMAGES:  CDC, USDA, EPA, USDA**

**Notes:**
Some of the chemical warfare agents are said to have characteristic odors, such as those listed here.  However, these are not adequate warning properties for the purpose of protecting yourself against adverse health effects associated with exposure, as we shall see in a moment.

## Nerve Agent History

**Nerve Agent History**

- Organophosphates (Ops) known in 1800s
- 1936:  GA (Tabun)
- 1938:  GB (Sarin)
- 1944:  GD (Soman)
- Early 1950s:  VX
- Germany had in munitions in WWII
- Used by Iraq
- In stockpiles
- U.S. has VX, GB, minimal GA

**IMAGES:  CIA**

**Notes:**
The first of what we know today as a nerve agent was synthesized in pre-World War II in Germany by Dr. Gerhard Schrader, a chemist at IG Farben who had been conducting a search for more effective pesticides.  The code names of Wehrmacht nerve agents were standardized by the Tripartite Pact, the precursor of the North Atlantic Treaty Organization (NATO), as GA for Tabun, GB for Sarin, and GD for Soman.  The G was to stand for German, as in German A, German B, and so on.  Germany had stockpiles of G-agent munitions during World War II but did not use them for reasons which are still unclear.  In 1952, Dr. Ranajit Ghosh in England was conducting research for new pesticides to replace DDT, when he discovered an organophosphonate that was extremely toxic to mammals as well as insects.  This information was passed to the British military laboratory at Porton Down, and the technology was soon passed on to the United States.  Despite their potency and half-century of availability, nerve agents have only been used on the battlefield during the Iran-Iraq conflict.  The present U.S. chemical weapons stockpile contains the nerve agents GB and VX, and a very small amount of GA at one site.  Other experimental agents such as GD and GF are used in small amounts in research and development facilities. The greatest threat of human exposure today exists in laboratories in storage and disposal facilities where nerve agents are present or in terrorist events like those that occurred in Matsumoto in 1994 and in the Tokyo subway in March 1995.

## Chemical Agent Terrorist attacks

**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

**IMAGES:  CIA **

**Notes:**
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 about 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 5,500 who sought medical care.  Over 80 percent of those found their own transportation to the medical facilities.  One hundred thirty-five (135) of the first responders were injured. 
Hospital Lessons Learned [Vapor Exposure]
Clothing removal and shampooing of hair removes most of vapor exposure
First responders were not in adequate PPE
Chemical events need systems in place for event management

INSTRUCTOR NOTE:  Much confusion initially surrounded the Matsumoto attack.  Early news reports blamed the incident on a local resident attempting to make insecticide for his garden.  In reality, the Aum cult had used a 2-ton truck equipped with a heated vat of sarin and a computerized fan to disseminate it.  They originally planned to attack three judges in their courthouse (shown above), but later attacked their residence building instead.  Estimates of injuries vary, but range as high as 280 to 500 people.

## Physical Properties

**Physical Properties**

- Clear, colorless liquids (when pure)
- Not “nerve gas”
- Tasteless, most are odorless
- Freeze/melt <0oC
- Boil >150oC
- Volatility GB>GD>GA>GF>VX
- Penetrate skin, clothing

**Notes:**
The nerve agents are not “nerve gas” as they are commonly called, but are clear, colorless liquids, at least in their pure states.  They are said to be tasteless, and most are odorless, although GA and GD are said to have slight odors.  Their freezing/melting points are below 0C, and their boiling points are above 150C.  They are heavier than water, and their vapor densities are much greater than that of air.  Their vapors sink into valleys, trenches, and basements.
Their volatilities, or tendency to evaporate and form a vapor, vary.  The G-agents are more volatile than VX; the volatility of GB approximates that of water.  GF is the least volatile of the G-agents, which means that it evaporates slower from terrain and equipment in a hot climate.  VX has a volatility similar to that of a light motor oil and is not likely to present a vapor hazard in a temperate climate.  Most casualties from the G-agents have been from vapor exposure. GB is similar to gasoline.
All of these agents penetrate skin rapidly and readily.  However, small amounts of the G-agents tend to evaporate rather than penetrate when placed on skin, unless they are occluded and prevented from evaporating.  All penetrate normal clothing. 

## Toxicity

**Toxicity**

-         LCt50 (mg-min/m3)                     LD50 (mg/70kg)
- 		GA		400		     	1,000
- 		GB		100		     	1,700
- 		GD	 	  70		              50
- 		GF	  	  50		              30
- 		VX		  10		              10

**Notes:**
LCts are measurements of approximately how much of a particular compound is needed to induce fatal effects for 50% of the population.  This measurement is based on an average healthy person, with no underlying disease processes.  Clinicians must keep in mind that those persons who have pre-existing conditions (primarily respiratory) may be more susceptible to effects of the agent than other people.  LCt50 specifically stands for Lethal Concentration times time for 50% of the population, and is primarily a vapor or aerosol measurement. Median lethal concentration for 100 people who are exposed there will be 50 affected.
The LD50 is a measurement of the actual dose, in milligrams per unit of weight.  This specifically stands for Lethal Dose for 50% of the population.  Again, this is based on healthy persons without underlying disease.  LD50 measurements are primarily for quantifying liquid exposures for a 70 kilogram person.
The estimated LCts of the nerve agents are about 400 mg-min/m3  for GA, 100 mg-min/m3 for GB, 70 mg-min/m3 for GD, 50 mg-min/m3 for GF, and slightly lower for VX.  The estimated LD50s for liquid on skin are estimated to be 1,000 mg for GA, 1,700 mg for GB, about 50 mg for GD, 30 mg for GF, and 10 mg for VX.

## Examples of AChE Inhibitors

- Carbamates
- Physostigmine (Antilirium®)
- Neostigmine (Prostigmine®)
- Pyridostigmine (Mestinon®)
- Sevin® (insecticide)
- Organophosphates
- Malathion
- Diazinon
- “Nerve Agents”

**IMAGE:  USGS **

**Notes:**
The nerve agents belong to a class of chemicals called organophosphates and have a physiological effect similar to that of many insecticides commonly found in the community, such as malathion, diazinon, and chlorpyrifos.

## Nerve Agent

- A substance that causes biological effects by inhibiting acetylcholinesterase (AChE) allowing excess acetylcholine (ACh) to accumulate in the synaptic junction
- Effects are due to excess acetylcholine

**Notes:**
Nerve agents act by inhibiting cholinesterase enzymes at different locations within the central, peripheral, and autonomic nervous systems.  Acetylcholinesterase is responsible for the hydrolysis of the cholinergic neurotransmitter acetylcholine (ACh).  Cholinesterase (ChE) enzymes are present in blood, brain, muscle, and other effector organ sites.  Blood cholinesterases include butyrylcholinesterase in the plasma and erythrocyte cholinesterase (ChE) in the red blood cell (RBC).  The plasma and RBC-ChE enzymes provide an estimate of tissue enzyme activity, and may be used to monitor those who work around cholinesterase‐inhibiting substances, such as organophosphorus pesticides, carbamates, or nerve agents.  Organophosphorus pesticides preferentially inhibit either plasma cholinesterase or RBC-ChE.  Both GB and VX inhibit RBC-ChE to a greater extent than plasma ChE following exposures.  This information is important to consider when attempting to confirm the presence of a mild or moderate exposure.  Following high‐level exposures, both plasma and RBC‐ChE activities will be significantly depressed.  The time course for RBC‐ChE depression is rapid.  Maximal inhibition of RBC-ChE activity may occur within seconds to minutes after vapor exposures, and within several hours following liquid percutaneous exposures.  During the recovery phase, the plasma enzyme activity more closely parallels tissue enzyme activity.  RBC-ChE activity recovers at the rate of erythrocyte replacement (about 1 percent per day) following GB exposures.  Recovery of RBC‐ChE activity is more rapid following VX exposures due to the spontaneous reactivation of agent‐bound enzyme.  Tissue and plasma ChE activities return with the synthesis of a new enzyme.

## Normal Nerve Function

**IMAGE:  DOD **

**Notes:**
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.
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.
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.
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.
The 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.

## Effects Of Nerve Agents

- Organs with cholinergic receptors
- Muscarinic
-  Smooth muscles
-  Glands
- Nicotinic
-  Skeletal muscles
-  Ganglia

**Notes:**
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.
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. 
ACh is a chemical messenger. One analogy that can be used is that typically a stoplight is going to manage traffic flow from different directions. But with a nerve agent exposure: the green light on the traffic column is left on. Therefore, the ACh continues to flow unmonitored because the green light is left on.

## SLUDGE

-  S = Salivation
-  L = Lacrimation
-  U = Urination
-  D = Defecation
-  G = Gastrointestinal Distress
-  E = Emesis

**Notes:**
SLUDGE is a useful acronym to serve as a reminder for several of the major physiological effects of nerve agents. Salivation and lacrimation occur as a result of excess acetylcholine stimulating exocrine glands. Urination, defecation, and GI distress are due to the excess smooth muscle stimulation. Nausea and vomiting are early signs of skin exposure.

## Signs And Symptoms Muscarinic Sites

- Increased secretions
- Saliva
- Tears
- Runny nose
- Secretions in airways
- Secretions in gastrointestinal tract
- Sweating

**IMAGE:  DOD **

**Notes:**
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. Of particular importance in the early management of the casualty are the copious bronchial secretions. The excess secretions in the airway coupled with bronchoconstriction produced by smooth muscle contraction can be life threatening.

## Signs And Symptoms Muscarinic Sites

**Signs And Symptoms Muscarinic Sites**

- Smooth muscle contraction
- Eyes: miosis (constriction)
- Airways:  bronchoconstriction (shortness of breath)
- Gastrointestinal:   hyperactivity (nausea, vomiting, and diarrhea)

**IMAGE:  DOD **

**Notes:**
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.
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 Nicotinic Sites

**GB**

**Signs and Symptoms Nicotinic Sites**

- Skeletal muscles
- Fasciculations
- Twitching
- Weakness
- Flaccid paralysis
- Other (ganglionic)
- Tachycardia
- Hypertension

**IMAGE:  SAIC **

**Notes:**
This is a drawing of smooth muscle being continuously stimulated by acetylcholine. The blue dots represent AChE, the larger brown dots are acetylcholinesterase and the black ‘squares’ is nerve agent that is blocking the action of the acetylcholinesterase resulting in the continuous stimulation of the smooth muscle fibers. 
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.

## 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

**IMAGE:  USAF **

**Notes:**
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.

## Signs And Symptoms Vapor Exposure

- Mild exposure
- Miosis with 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
- Effects occur within seconds, peak within minutes; no delayed onset

**Notes:**
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. 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 Liquid Exposure

- Mild exposure (onset of symptoms up to 18 hrs)
- Localized sweating
- Fasciculations
- No miosis
- Moderate exposure (<LD50) (onset of symptoms up to 18 hours)
- Gastrointestinal effects
- Miosis uncommon

**Notes:**
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.  
Delayed onset of symptoms indicates a percutaneous exposure and potential worsening of S&S. Care must be taken with these casualties as they may progressively deteriorate and require additional antidote during transport and for several hours post exposure.
A case study involving a soman exposure is well documented in the Textbook of Military Medicine. A 33 year old man working with soman in solution  [25% (V/V) concentration with the total volume < 1 ml] when a syringe - needle connection broke and splashed some of the solution into and around his mouth. He immediately washed his face and rinsed his mouth and was brought to the emergency room. 5 - 10 minutes after the exposure he collapsed. Physical examination showed that he was comatose, mildly cyanotic with slightly labored respirations, miosis, markedly injected conjunctiva, marked oral and nasal symptoms, moderate trismus and nuchal rigidity, prominent fasciculations, and hyperactive deep-tendon reflexes. He was treated with Atropine [4 mg IV and 8 mg IM] and pralidoxime chloride [2 gm IV over 30 minutes]. Within 30 minutes, his condition began to improve. 

## Signs And Symptoms Liquid Exposure

- Severe exposure (LD50) (onset of symptoms <30 minutes)
- Sudden loss of consciousness
- Seizures
- Apnea
- Flaccid paralysis
- Death

**IMAGE:  SAIC**

**Notes:**
The graphic depicts an LD50 dose of VX (10 mg).  A droplet of this size on the skin will produce a Lethal Dose for fifty percent of the exposed population (LD50).  This exposure could potentially cause severe symptoms, such as sudden loss of consciousness, seizures, flaccid paralysis, and apnea will occur within minutes.
One example to explain the effects of an LD50 of VX would be 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 serious but 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

**Notes:**
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.  However, two or more signs and symptoms must be present before administering antidote.
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. In fact, an astute triage team recognizing the signs and symptoms of chemical agent exposure can direct the initial detection team to confirm their diagnosis. The detection team will need to continue their analysis to rule out a multiple chemical event.

## Nerve Agent Treatment

- Airway/ventilation
- High resistance
- Antidotes
- Atropine
- 2-PAM Cl
- Benzodiazepine
- Valium
- Versed

**IMAGE:  USMC**

**Notes:**
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 a benzodiazepine (Valium or Versed).  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.
It is important to remember 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
- Given IV in hypoxic patient may cause ventricular fibrillation

**Notes:**
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.

## Nerve Agent Treatment

- Starting dose - 2 mg atropine
- Enough must be administered to abate respiratory distress if casualty is to survive
- Insecticide poisoning requires more atropine than chemical warfare agents per equivalent amount
- Side effects in non-contaminated or non-exposed people
- Mydriasis
- Blurred vision
- Tachycardia
- Decreased secretions and sweating

**Notes:**
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

**Notes:**
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.
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

**Nerve Agent Treatment**

- Pralidoxime Chloride (2-PAM Cl)
- Removes nerve agent from AChE in absence of aging
- 1 gram slowly (20-30 minutes) in IV infusion
- Hypertension with rapid infusion
- For IM use, up to 1.8 grams
- No effects at muscarinic sites
- Helps at nicotinic sites

**IMAGE:  SAIC**

**Notes:**
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. The soman-enzyme complex ages in about 2 minutes.  The speed with which Soman ages probably will not be significant from the immediate medical treatment standpoint for two reasons:

The exact identity of the chemical agent (Soman vs. other nerve agents) probably will not be immediately known after an attack.
The amount of 2-PAM Cl used will not harm the patient.

Administration of the 2-PAM Cl should be by slow IV infusion, over 20 to 30 minutes.  Rapid IV infusion will produce hypertension.  Patients receiving IV infusions should be monitored for arrhythmias. The oxime can also be given IM, 600 mg per unit dose, as in the MARK I autoinjector. 

## Treatment - Autoinjectors

**Treatment - Autoinjectors**

- 600 mg pralidoxime chloride (IM) in injector #2
- 2 mg atropine (IM) in injector #1

**IMAGE:  SAIC**

**Notes:**
Atropine and pralidoxime chloride (2-PAM Cl), are used by the military in autoinjectors which together are called the Mark I Antidote 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-PAM Cl. The Food and Drug Administration (FDA) has approved the autoinjectors for adults and pediatrics, but local protocol will determine their use in the field.

INSTRUCTOR NOTE:  A demonstration of Mark I Antidote Kit administration can be performed at this point.  This may be accomplished by firing a kit through a piece of cardboard or into a sandbag.  It is very important to encourage proper technique (no fingers over either end) and prompt disposal of the kit after use into an approved sharps box.

## Autoinjection vs. IM Or IV

**Source Unknown**

**IMAGE:  DOD**

**Notes:**
Using cardiac response as an indicator of atropine uptake over time, the above chart demonstrates the effectiveness of the Mark I autoinjector 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 autoinjection effects are also seen to be of comparatively long duration.

## Mark I Autoinjector - Dispersal

**Mark I Autoinjector - Dispersal**

**IMAGE:  DOD**

**Notes:**
Rapid absorption of antidote following automatic injection is enhanced by the degree of tissue dispersion achieved by the autoinjector.  The radiograph shows IM autoinjector doses (on left) compared to standard syringe IM doses (on right).  The autoinjector medication is obviously more efficiently diffused into surrounding muscle due to the force with which it is expelled from the injector (as seen in the above photo).

## Nerve Agent Treatment

**Nerve Agent Treatment**

- A benzodiazepine
- Decreases seizure activity
- Reduces seizure-induced brain injury
- Given to casualties with severe symptoms whether convulsing or not
- 10 mg increments, titrate to effect

**IMAGE:  DOD**

**Notes:**
Seizures are treated with benzodiazepines such as diazepam lorazepam or midazolam.  These medications can be administered IV or diazepam 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 Antidote 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.  
Diazepam is recommended because the FDA has approved its use in nerve agent-induced seizures.  The military fields this medication only for anticonvulsant use.  Many emergency departments have other benzodiazepines more readily available.  Animal data indicates that the other benzodiazepines are as efficacious as diazepam, and in particular midazolam (Versed) may work faster but has a shorter duration than others in this class.

## Nerve Agent Treatment

- Treatment regimen
- No signs/symptoms or miosis only
- Reassure
- Observe
- Vapor:  1 hour
- Liquid:  Up to 18 hours

**IMAGE:  EPA**

**Notes:**
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). Also, individuals with miosis in the absence of additional S&S should not receive antidote.

## Nerve Agent Treatment

**Nerve Agent Treatment**

- Mild vapor exposure
- Miosis, rhinorrhea - observation only
- Increasing SOB - treat
- Mild liquid exposure
- Localized fasciculations & sweating - treat

- One Mark I Antidote Kit (2 mg atropine/ 600 mg 2 –PAM Cl) IM
- 	 _OR_
- 1 gram 2-PAM Cl IV
- 2 mg atropine, IM or IV
- 	Parenteral atropine will not reverse miosis

**Notes:**
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 and 600 mg of 2-PAM Cl, or with the Mark I Antidote 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-PAM Cl IM (Mark I Antidote Kit) or 1 gram (gm) 2-PAM Cl IV slowly over 20 to 30 minutes.
After the 1995 Tokyo subway nerve agent attack, 95 percent of symptomatic casualties suffered only from miosis.
Note:  This pralidoxime administration can be provided via Mark I Antidote Kit or by reconstituting powdered 1 gram vials with 3.3 ml of sterile water.  An infusion may be mixed with the following ratio: 1 g of 2-PAM Cl in 250 ml of Normal Saline and infused over a 20-30 minute period.

## Nerve Agent Treatment

- Moderate vapor or liquid exposure
- One or two Mark I Antidote Kits
- Or give IV:
- 2 to 4 mg atropine initial dose
- 1gm 2-PAM Cl (infusion)
- Titrate to effect

**IMAGE:  USAF **

**Notes:**
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 Antidote Kits each containing a total of 2 mg atropine and 600 mg 2-PAM Cl.  Treatment may also be given IV, with 2 to 4 mg atropine given IV push, and 1 gram of 2-PAM Cl 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-PAM Cl for a total of 1,800 mg 2-PAM Cl with the Mark I Antidote Kit IM (or 1 gm 2-PAM Cl IV over 20 to 30 minutes).
Moderate Liquid Exposure:  For moderate toxicity several hours after liquid exposure, 2 mg of atropine and 600 mg 2-PAM Cl should be given initially.  Repeated doses of atropine and 2-PAM Cl 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.

## Nerve Agent Treatment

- Severe - vapor or liquid
- Give 3 Mark I Antidotes Kits or 6 mg atropine and 1 gram of 2-PAM Cl as soon as possible
- Airway
- Ventilation/Oxygen
- Diazepam 10 mg (2 to 5 mg increments, IV or IM)
- Repeat atropine every 5 to10 minutes as needed
- Repeat 2-PAM Cl in one hour

**Notes:**
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 of atropine IM immediately, and 2-PAM Cl should be started.  Alternatively, 3 Mark I Antidote Kits should be given as quickly as possible, with diazepam administered immediately to avoid or control seizures. These patients will require assisted ventilation with oxygen.
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 - Initial treatment
- Infants & children (IV/IO/IM)   0.02 mg/kg
- IM
- Infant (0 to 2)		0.5 mg
- Child (2 to 10)		1.0 mg
- Elderly			1.0 mg

**Notes:**
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.
Category		Age		Dose		
Infant		0 to 2 years	0.5 mg single dose
Child		2 to 10 years	1.0 mg single dose
Adolescent		Young adult	2.0 mg single dose	
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 Antidote 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.

## Nerve Agent Age-related Treatment

- 2-PAM Cl
- < 20 kg		15 mg/kg IV
- Elderly		1/2 adult dose (7.5 mg/kg IV)
- > 20 kg		600-mg IM autoinjector
- 2 PAM Cl-induced hypertension
- Phentolamine	Adult	 	5 mg IV
-    (regitine)		Child		1 mg IV

**Notes:**
Pralidoxime Chloride:  No data are available for 2-PAM Cl 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.  For IM use, the doses should be :

Weight		  Dose		
	           < 20 kg	           15 mg/kg			 < 20 kg	       	600 mg autoinjector
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-PAM Cl (7.5 mg/kg IV).
If hypertension becomes significant during the administration of the 2-PAM Cl, treat with IV phentolamine as follows:
Adult:  5 mg IV
Child:  1 mg IV

## Nerve Agent Age-related Treatment

- Diazepam
- Children > 30 days old to 5 years
- 0.2 - 0.5 mg/kg IV q 2 to 5 min (max 5 mg)
- Children > 5 years
- 1 mg IV q 2 to 5 min (max 10 mg)

**Notes:**
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
Children > 5 years		1 mg IV every 2 to 5 minutes to 			maximum dose of 10 mg

## Nerve Agent Summary

- _Vapor 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

**Notes:**
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 Agent Summary

- _Liquid exposure_
- Symptoms delayed minutes to hours
- Greater need for decontamination
- High risk of secondary contamination; victims require decontamination
- Requires immediate access to antidotes

**Notes:**
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 be provided simultaneously with antidote administration and airway management, when necessary. 

## Blister Agents Or Vesicants

- Definition
- Military vesicants
- Sulfur mustard
- Lewisite
- Other vesicants
- Riot control agents
- Poison ivy, poison oak & sumac
- Industrial chemicals
- Sunlight
- Cancer chemotherapeutics

**IMAGES:  DOD, NIBB/USGS, CDC, DOD**

**Notes:**
Vesicants cause blistering.  They may be plant, animal, chemical, or sunlight.  Those to be discussed are the chemical warfare vesicants, namely sulfur mustard and Lewisite.  A close relative of sulfur mustard, nitrogen mustard, was the first cancer chemotherapeutic agent.

## Mustard

- Vapor and liquid threat
- Latent period between exposure and effects
- Topical eye, skin, and airway damage
- Treatment is symptomatic
- Systemically toxic; damages bone marrow

**IMAGE:  DOD**

**Notes:**
Sulfur mustard is a vesicant or blister agent, which is 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.

## Mustard - Onset

- Chemical cell damage:  1 to 2 minutes
- Clinical effects:  2 to 48 hours; usually 4 to 8 hours
- Initial responders will not see these casualties at the scene, but may be called upon to transport them hours later when they manifest symptoms

**IMAGE:  DOD**

**Notes:**
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, there is no immediate skin discoloration, and there is no immediate eye irritation.  Hours later, the casualty realizes 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.

## How Mustard Works

- Quickly cyclizes in tissue
- Alkylates cell components, such as  DNA
- DNA damage, cell death
- May affect eyes, skin, and respiratory tract
- Vesicle fluid does not contain agent

**IMAGE:  SAIC**

**Notes:**
Despite years of research, the exact mechanism by which mustard damages cells is unknown.  It alkylates cell components, such as DNA, and clings to proteins and other cellular components.  The end result is DNA damage and cellular death.  Mustard agent is a radiomimetic agent, which means that the injury is very similar to that produced by radiation.  As mentioned earlier, the three organ systems directly affected topically by mustard are the eyes, skin, and respiratory tract. The eyes are the most sensitive “organ” to sulfur mustard [HD] exposure.

INSTRUCTOR 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 Eye Effects

- Mild conjunctivitis
- Moderate/severe conjunctivitis, lid inflammation and edema, blepharospasm, corneal roughening
- Corneal opacification, ulceration, and/or perforation
- 85% of the mustard casualties had mild to moderate conjunctivitis (WWI)
- Under 1% had permanent damage to cornea by liquid

**Notes:**
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 (involuntary eye closure), 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.  Miosis is sometimes observed after mustard exposure and is thought to be due to cholinergic effects.

## Mustard Skin Effects

- Erythema
- Small vesicles; later coalesce
- Blisters/bulla
- Possible coagulation necrosis with liquid agent exposure

**IMAGES:  SAIC**

**Notes:**
Skin effects begin hours after exposure with erythema (redness, irritation) 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 (liquid to solid) necrosis (cell death) extending into the dermis (skin) 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.

## Mustard Airway Effects

- Upper
- Nose bleeding
- Sore throat
- Hacking cough
- Mid:  Larynx (hoarseness)
- Lower:  Bronchioles (dyspnea, productive cough)
- Pulmonary edema rare

**Notes:**
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.  With increased concentration and exposure, the more severe the response.  After a small exposure or initial phase of a large exposure, there may be epistaxis, sinus discomfort, and a mild to moderate pharyngitis with a hacking cough.  After a moderate exposure or progressive phase of a large exposure, there may be laryngitis with voice loss and a productive cough.  

## Mustard Airway Effects

**Mustard Airway Effects**

- Cross-section of airway bronchiole with necrosis and sloughing of tissue occluding the lumen

**IMAGE:  DOD**

**Notes:**
If the exposure is large, the agent reaches the smallest airways to cause dyspnea and productive cough.  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.

## Mustard Bone Marrow Effects

- Damages stem cells
- Decreased WBC, RBC, platelets
- Survival rare if WBC < 200 (normal = 3,000 to 10,000)

**IMAGE:  NASA**

**Notes:**
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 quite large, there is no recovery and the cell count will reach zero.  Survival usually does not occur when this happens.  The red blood cells and platelets also decline following the white blood cells.  The absence of these cells increases susceptibility to infection and contributes to death. Mustard exposure treatment with colony stimulating factors such as Neupogen ® and Neulasta ® have not been studied but could provide increased white blood cells to ameliorate the infectious process.

## Mustard Gastrointestinal Effects

**Mustard Gastrointestinal Effects**

- Within 24 hours
- Nausea, vomiting, diarrhea
- After 3 to 5 days
- May have tissue destruction

**IMAGES:  SAIC, USN / CDC**

**Notes:**
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. Hematemesis and diarrhea [sometimes bloody] can also develop.
Gastrointestinal effects seen after 3 to 5 days are thought to be due to tissue destruction in the abdomen.

## Mustard Skin Decontamination

- Part of supportive treatment
- Physical removal of agent
- Remove clothing
- Flush skin with soap and water
- Flush eyes with sterile saline or sterile water
- Must be done within 2 minutes to prevent damage
- Delays in decontamination will not prevent illness,         **but will prevent cross-contamination**

**Notes:**
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.  Skin decontamination may be performed with soap and water.  Decontamination must be done as quickly as possible since cellular damage occurs in as little as two minutes.  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.

## Mustard Treatment

- Administer oxygen/intubate if indicated
- Administer bronchodilators if indicated
- Cover/shield eyes (no pressure) after flushing if pain associated with light
- Reassure patient

**Notes:**
Upper or minor airway symptoms (sore throat, non-productive cough, and hoarseness) may be relieved by humidified air/oxygen 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 severe upper airway 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.
A discussion of the therapy for ocular exposures is best begun by repeating the observation that mustard fixes/adheres 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 (pupil dilators) should be applied topically to prevent synechiae (scar) 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 vaseline should be applied to lid edges to prevent them from adhering.  

## Lewisite

- Vesicant effects similar to sulfur mustard
- Causes severe irritation immediately upon exposure to eyes, skin and airways
- Produces skin blisters, eye and lung injury, and pain
- No bone marrow effects

**IMAGES:  USN / CDC-NIOSH**

**Notes:**
     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.  Unlike mustard, it does not damage the bone marrow.
Skin:  Lewisite causes greater skin damage than sulfur mustard.  A gray area of dead skin can progress to blisters and severe tissue necrosis and sloughing.
Lungs:  Since lewisite causes immediate irritation to the nose and sinuses, and effort by the victim to evacuate the area of contamination may prevent more severe lung damage.  Pseudomembrane (layer of dead tissue of the throat) formation is common.
Cardiovascular system:  Lewisite causes increased capillary permeability, leading to volume depletion and hepatic and renal injury.
     The above images, taken during the Gulf War of the early 1990s, shows injury attributed to Lewisite or a chemical agent similar to it.  It was contributed to the CDC/NIOSH educational program “Occupational Dermatoses” by U.S. Navy Captain James W. Steger, M.D.

## Lewisite Treatment

- Self protection
- Immediate decontamination
- British anti-lewisite (BAL)
- For systemic effects
- 2-5 mg/kg IV

**IMAGES:  SAIC**

**Notes:**
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.  As it is administered parenterally, BAL has no effect on Lewisite damage to the skin and eyes.

## Cyanide

- Widely used throughout the U.S.
- Printing
- Agriculture
- Photography
- Manufacturing of paper and plastics
- Over 300,000 tons produced annually
- Combustion byproduct of burning synthetic materials

**IMAGES:  USCG, USN**

**Notes:**
Cyanide is a chemical that is widely utilized, manufactured, and transported in the United States.  More than 300,000 tons of cyanide are produced annually.  It is used in printing, agriculture, photography, and in the manufacture of paper and plastics.  It is also a combustion product of burning synthetic materials.  Rail cars with 30,000-gallon tanks of cyanide represent potential transportation and terrorist threats.

## Cyanide
Salts (solids)
Sodium, potassium, calcium
Liquids
Hydrocyanic acid, cyanogen chloride
Bitter almond odor - unreliable since undetected by 40% of the population
Must be delivered in large quantities (bombs and shells) to produce death

- Salts (solids)
- Sodium, potassium, calcium
- Liquids
- Hydrocyanic acid, cyanogen chloride
- Bitter almond odor - unreliable since undetected by 40% of the population
- Must be delivered in large quantities (bombs and shells) to produce death

**Cyanide Characteristics**

**Notes:**
Cyanide is stored and utilized militarily in the liquid or solid state.  It may have an odor of bitter almonds, but the ability to smell the cyanide exists for only 40 percent of the population.

## Types Of Cyanide

- 			         Hydrocyanic               Cyanogen
- 			           Acid (AC)	              Chloride (CK)
- Vapor 	 		Lighter than air	  Heavier than air
- Density
- Odor			Bitter Almonds           Pungent
- Irritation		  None	                       Eyes, nose, throat

**Notes:**
The three types of cyanide that may be encountered are hydrogen cyanide (AC), cyanogen chloride (CK), and cyanide salts.  The term “cyanide” refers to the anion, CN, or to its acidic form, hydrocyanic acid (HCN).  Cyanogen (CN2) is formed by the oxidation of cyanide anions.  However, the term cyanogen has also come to mean a substance that forms cyanide upon metabolism and produces the biological effects of free cyanide.  Cyanogen chloride is a pungent, heavier-than-air vapor which can cause irritation of the eyes, nose, and throat.  This is in distinct contrast to hydrogen cyanide, which has no irritant properties.
Cyanide salts (for example, NaCN) are compounds that dissociate into the cyanide anion (CN-) and a cation (Na+).  Salts are most dangerous following ingestion; onset of action is slower and more prolonged.  Cyanide salts generate hydrogen cyanide gas on contact with a strong acid such as sulfuric acid.

## How Cyanide Works

- Small amounts
- Metabolized and excreted
- Minimal toxicity
- Large amounts
- Binds to iron in mitochondria preventing cells from using oxygen
- Without oxygen, cells die - heart and brain affected initially

**Notes:**
Cyanide exists normally in human tissues and is usually metabolized by hepatic enzymes (rhodanese) into thiocyanante, which is excreted in the urine.
Under normal conditions, the cyanide anion is attracted to iron in the ferric state (Fe+++).  In the mitochondrion of the human cell, cytochrome A3 in the cytochrome oxidase complex contains Fe+++.  Cyanide is bound to cytochrome A3 and thus inhibits the effect of the cytochrome oxidase.  This enzyme complex is responsible for the utilization of oxygen within the cell.  In the presence of cyanide, even though there is plenty of dissolved oxygen in the blood, the cells cannot use oxygen.  As a result, cells must utilize anaerobic metabolism, or the creation of energy without the benefit of oxygen, which causes a severe lactic acidosis.  When cells cannot get enough energy, they die. Cells in the brain and heart are affected initially.

## Acute Inhalational Cyanide Poisoning

- Low concentrations (non-lethal)
- Victims become anxious
- Hyperventilate
- Develop headache, dizziness, and vomiting
- Symptoms improve when victim is removed from the source

**Notes:**
Acute cyanide poisoning occurs after inhaling the agent, but may also occur after drinking solutions of cyanide (it is sometimes used with suicidal intent) or by skin contact with large amounts of liquid cyanide.  After inhalation of a low concentration, the patient may become anxious, will often hyperventilate, and typically develops a headache with dizziness and vomiting.   Skin color may initially be flushed but may also be normal or cyanotic.

## Acute Inhalational Cyanide Poisoning

- High concentrations (inhalation)
- 0 to 15 seconds - anxious and hyperventilate
- 0 to 30 seconds - seizures
- 3 to 5 minutes - breathing ceases
- 6 to 10 minutes - asystole -> death
- Normal or dilated pupils
- Initial absence of cyanosis
- Skin may be flushed or “cherry red” color (terminal finding)

**Notes:**
In about 15 seconds after inhaling a large amount of cyanide, victims become anxious and start to hyperventilate. Thirty seconds after exposure, the patient may begin to convulse.  In 3 to 5 minutes, breathing ceases.  Asystole or cessation of heart activity occurs in 6 to 10 minutes, followed by death. The patient may have normal sized or dilated pupils. Death can occur within 8 minutes of exposure. If a patient is exposed to a low concentration of vapor and removed from the source of the cyanide, the symptoms should not progress.
Pulse oximeter readings are unreliable indicators of tissue delivery of oxygen. The cells cannot use the oxygen carried in the blood. There is high oxygen content to venous blood because oxygen is not extracted from arterial blood by cells.  A metabolic (lactic) acidosis may also be present from the lack of oxygen to the tissues.  Cyanide toxicity can be measured at the hospital by checking serum cyanide concentrations.  These values may, however, only be available after a delay of several hours.

## Cyanide Inhalational Treatment Regimen

**Cyanide **_**Inhalational **_**Treatment Regimen**

- Remove from area; take off clothing
- If conscious and breathing - administer oxygen and observe; no antidotes
- If unconscious - administer oxygen, provide airway management, ventilate with bag-valve mask, administer cyanide antidote kit
- Mechanical resuscitation is required - no mouth-to-mouth

**Notes:**
Remove from area of exposure and remove clothing.
Mild exposure:  If conscious and breathing, give O2, IV fluids. Observe, no antidotes necessary.
Severe exposure:  If unconscious, whether breathing or not, give O2, and bag-mask ventilate with 100 percent O2.  Cardiac monitor.  Oxygen saturation may or may not be normal.
Amyl Nitrite Administration
Crush pearles into a 4 x 4 piece of gauze and place over face (however, if the patient is breathing, they probably do not need the drug) or in a bag mask.  Add another ampule every few minutes.  Give only until IV drugs are available.
When IV established, give sodium nitrite 300 mg (10 cc ampule) over 5 minutes for adults.  For children, use 0.2 to 0.3 mg/kg or 6 to 9 cc/kg of the 3 percent solution.  Watch for orthostatic hypotension (however, if the patient can stand, they do not need this).
Then, sodium thiosulfate 12.5 gms (50 cc) IV.  For children, use 0.4 mg/kg or 1/65 cc/kg of the 25 percent solution.

## Cyanide - Severe Inhalation                        or Symptomatic Ingestion

- Remove cyanide from the cell
- Cyanide likes to bind to iron (Fe+++)
- Convert hemoglobin (Fe++) → methemoglobin (Fe+++) using amyl nitrite/sodium nitrite
- Add sodium thiosulfate to complete detoxification
- Oxygen, hyperventilate, bicarbonate, IV fluids

**IMAGE:  DOD**

**Notes:**
Patients who have inhaled significant doses of cyanide must be rapidly treated with appropriate antidotes to prevent brain damage.  Cyanide is also attracted to iron (Fe+++) in a form of hemoglobin called methemoglobin.  In fact, cyanide will preferentially leave the cytochrome oxidase enzyme in the cell and bind to the circulating methemoglobin.  Drugs such as amyl nitrite and sodium nitrite, which are found in the cyanide treatment kit, increase blood concentrations of methemoglobin and are antidotal.  Adding sodium thiosulfate completes the detoxification process.
Patients should be treated with IV saline for hydration and sodium bicarbonate and hyperventilation (after intubation) for the metabolic acidosis.  Oxygenation should be maintained with high-flow oxygen by mask or by endotracheal tube.  Monitor and treat significant arrhythmias.

## Amyl Nitrite Perles
Break gauze, 30 seconds rx
Methemoglobin
Sodium Nitrite
300 mg (10 cc amp) over 5 min, hypotension
Sodium Thiosulfate
12.5 gm (50 cc amp) IV over 5 min
Thiocyanate in urine

- Break gauze, 30 seconds rx
- Methemoglobin
- Sodium Nitrite
- 300 mg (10 cc amp) over 5 min, hypotension
- Sodium Thiosulfate
- 12.5 gm (50 cc amp) IV over 5 min
- Thiocyanate in urine

**Cyanide - Severe Inhalation****or Symptomatic Ingestion ****(cont’d)**

**Notes:**
The Pasadena Cyanide Antidote Kit:  This kit (formerly known as the Lily Cyanide Kit) contains amyl nitrite, sodium nitrite, and sodium thiosulfate.  (This has a limited shelf life)
Amyl nitrite:  Amyl nitrite is available in perles which are broken and placed in either a gauze bandage or in the bag-mask and inhaled for 15 seconds, then taken away for 15 seconds (although, if the patient is breathing, he probably does not need the antidote).  This is the initial step in antidote therapy.  Amyl nitrite is a methemoglobin former and reduces the elevated total peripheral resistance caused by the acidosis and cyanide.  This should be used only until the IV drugs can be given.  This will cause orthostatic hypotension. However, if the patient can stand, he or she does not need the antidote.
Sodium nitrite:  Sodium nitrite is a strong methemoglobin former that is available for IV use in a dose of 300 mg in 10 cc.  This dose is injected over 5 minutes and has a potential side effect of orthostatic hypotension.  Normal saline infusion and supine posture can help to correct the hypotension.  However, if the patient can stand, they do not need the sodium nitrite.  The pediatric dosage is 0.2 mg/kg, not to exceed 10 cc. The adult dose has been administered to children with lethal results. Formation of methemoglobin was too great to support oxygenation and death resulted.
Sodium thiosulfate:  This compound is a co-factor for the enzyme rhodanese for detoxification (to change cyanide to a form that can be excreted by the kidneys).  The drug is administered in a 50-cc ampule (12.5 gms) over 5 minutes IV.

## If cyanide antidotes available
Amyl nitrite - give until IV started
Sodium nitrite IV
Sodium thiosulfate IV
If cyanide antidotes not available
Intubate/hyperventilate
Administer oxygen
Administer IV fluids/sodium                            bicarbonate

- Amyl nitrite - give until IV started
- Sodium nitrite IV
- Sodium thiosulfate IV
- If cyanide antidotes not available
- Intubate/hyperventilate
- Administer oxygen
- Administer IV fluids/sodium                            bicarbonate

- Cyanide - Severe Inhalationor Symptomatic Ingestion (cont’d)

**IMAGE:  SAIC**

**Notes:**
Cyanide antidotes are usually available in limited amounts.  For single exposures where only one patient is exposed, hospitals will most likely be able to treat appropriately.  However, few facilities have multiple doses of cyanide antidotes, and other treatment methods must be employed until the antidote becomes available. 

## Chemical Weapons Differential Diagnosis

- _Nerve Agents_
- Miosis
- Copious secretions
- Muscle twitching
- Convulsions
- GI effects (nausea, vomiting, diarrhea)

- _Cyanide_
- Pupils normal
- Few secretions noted
- No twitching
- Convulsions
- Nausea only

**Notes:**
The following slides provide a review of signs and symptoms for those personnel potentially exposed to a chemical agent.  Although many have similar signs and symptoms, specific combinations will greatly assist in the identification of the specific material.

## Pulmonary Intoxicants(Phosgene, Chlorine, Ammonia)

- Cause severe life-threatening injury after inhalation
- Adverse effects often delayed
- Treatment is supportive

**IMAGE:  DOD**

**Notes:**
Pulmonary intoxicants cause severe life-threatening lung injury after inhalation.  These effects are generally delayed several hours after exposure.  Treatment is usually supportive and may require advanced intensive care techniques including intubation, use of a mechanical ventilator in the hospital, and PEEP breathing.  Pulmonary intoxicants included with this group are phosgene and chlorine.

## Phosgene

- Manufacturing of dies, coal tar, pesticides, pharmaceuticals
- Used in WWI

**IMAGE:  National Archives**

**Notes:**
Phosgene is widely used today in the manufacturing of dyes, coal tar, pesticides, and pharmaceuticals.  It was widely used in WWI until mustard was introduced on the battlefield.  The National Archive photo shows a World War I unit practicing gas mask donning.

## Phosgene (cont’d)

**Phosgene (cont’d)**

- 1984 Bhopal tragedy
- 50,000 lbs. methylisocyanate released
- 150,000 affected
- 10,000 severely injured
- 3,300 killed
- Phosgene and isocyanate injuries

**IMAGES:  CIA**

**Notes:**
The Bhopal, India disaster of 1984 at the Union Carbide plant involved the release of 50,000 pounds of methylisocyanate.  This chemical is composed of phosgene and methylamine.  There were 150,000 people affected, 10,000 severely injured, and 3,300 killed.  The effects of the release were thought to be due to a combination of isocyanate and phosgene.

## Phosgene - Characteristics

- Colorless gas (white appearance may be due to water vapor)
- Smells like freshly mown hay
- Four times heavier than air
- Converts to a gaseous state above 47°F

**Notes:**
Phosgene has a characteristic odor of freshly mown hay and is four times heavier than air.  It is a gas above 47 degrees F, and is principally a hazard by inhalation.

## Phosgene - Toxicity

- Inhalation hazard
- Phosgene + Water = Carbon dioxide  + Hydrochloric Acid
- When phosgene comes in contact with mucous membranes, it will produce irritation to eyes, nose, throat, and airways with delayed injury
- Mild cough, transient

**Notes:**
The primary damage from phosgene is from the carbonyl group.  Phosgene dissolves slowly in water to form carbon dioxide and hydrochloric acid (HCl).  In contact with the upper airways, HCl causes a transient irritation of the eyes, nose, sinuses, and throat.  It can also irritate the upper airway and bronchi, causing a dry cough. Because the upper respiratory tract is little affected, warning signs of exposure are slight, and symptoms may fail to appear for from 2 to 24 hours after exposure. However, the release of hydrochloric acid in the lungs causes pulmonary edema and may also cause bronchial pneumonia and lung abscesses; in severe cases death may result within 36 hours.

## Phosgene - Toxicity (cont’d)

- Penetrates slowly down airways
- Symptom-free period (2 to 24 hours)
- Carbonyl group attacks alveolar capillary membrane leakage of fluid into air cells
- Up to 1 liter per hour
- Patients become severely short of breath (non-cardiogenic pulmonary edema) and hypotensive
-  **NO DIURETICS**

**Notes:**
Phosgene penetrates poorly into the airways due to its poor water solubility.  There is a symptom-free period of 2 to 24 hours.  Over the first several hours, the carbonyl group from the phosgene attacks the surface of the alveolar capillaries.  Eventually, this causes the leakage of serum from the capillaries in the lung into the alveolar septi.  The fluid fills the tissues, causing severe hypoxia and apnea.  As the fluid leaks into the alveoli, massive amounts of fluid (up to 1 liter per hour) pour out of the circulation. The leakage of fluid in the lungs causes volume depletion.  Although the patient clinically looks like traditional heart failure, DO NOT USE DIURETICS!  These patients are volume depleted.  Treat hypotension with fluids.  These patients may require intubation and PEEP.

## At the scene
ABCs
Remove from source of exposure
Keep victims quiet, do not allow them to ambulate
Transport by stretcher
Decontaminate by removal of clothing prior to transport
NO EXERTION

- ABCs
- Remove from source of exposure
- Keep victims quiet, do not allow them to ambulate
- Transport by stretcher
- Decontaminate by removal of clothing prior to transport
- _NO EXERTION_

**Phosgene - Treatment**

**IMAGE:  DOD**

**Notes:**
Upon arrival at the hospital, the initial examination of a patient, symptomatic or not, should include - as a minimum - auscultation, chest x-ray, and arterial blood gases.  If the victim develops severe dyspnea due to upper airway irritation, early intubation should be considered to manage oxygen delivery and to prevent laryngeal spasm.  The airway should be suctioned frequently to remove secretions.  According to some authorities, antibiotic use should be guided by gram stain and culture results.  Another source recommends prophylactic antibiotics, as autopsy studies show uniform evidence of pneumonia and bronchitis.

## During transport
ABCs
SpO2 monitoring
NO EXERTION
For Advanced Providers
IV Fluids
Bronchodilators
Need for positive pressure ventilation may necessitate early intubation
NO DIURETICS

- ABCs
- SpO2 monitoring
- _NO EXERTION_
- For Advanced Providers
*IV Fluids*
*Bronchodilators*
*Need for positive pressure ventilation may necessitate early intubation*
- _NO DIURETICS_

**Phosgene - Treatment (cont’d)**

**IMAGE:  DOD**

**Notes:**
Ventilator management, PEEP, and oxygen administration might require consultation with a pulmonologist.  Fluid hydration may be necessary to treat the hypotension, bradycardia, or impending renal failure.  Diuretics such as Lasix are contraindicated because of the hypotension and the noncardiac nature of the non-cardiogenic pulmonary edema.  Standard  bronchodilators will usually control bronchospasm, but if not, steroids may be needed for this purpose.  Routine steroid use is controversial, but they seemed to offer some efficacy after the Bhopal tragedy.  Once the patient recovers, there should be little residual pulmonary effect.

## Ammonia

- Colorless, water-soluble, alkaline gas
- Pungent odor
- Wide industrial use
- Used to make fertilizer, explosives, dyes, and plastics

**IMAGE:  OSHA**

**Notes:**
Ammonia is a colorless, highly water-soluble, alkaline gas that has a pungent odor.  It is widely used industrially in the U.S. with over 500,000 workers potentially exposed annually.  It is used as an agricultural fertilizer and is used in the manufacture of explosives, dyes, and plastics.

## Ammonia - Characteristics

- Rapidly absorbed by mucosal surfaces (eyes, throat, and lungs)
- Corrosive produced when combined with water
- Liquefaction necrosis
- Household ammonia pH < 12
- Limited damage
- Anhydrous ammonia pH > 12
- Extensive damage

**Notes:**
Ammonia is rapidly absorbed by mucosal surfaces and causes damage to the eyes, oral cavity, throat, and lungs.  When mixed with water, it forms a corrosive agent, ammonium hydroxide (NH4OH - a potent alkali) which causes considerable damage in the form of liquefaction (solid to liquid) necrosis (cell death).  Due to its high water solubility, it penetrates rapidly into tissue.  Household ammonia generally has a pH less than 12 and generally causes limited damage to eyes or mucosa.  

## Ammonia - Clinical Signs

- Eyes
- Burning, tearing, severe pain -> injury to the cornea and lens
- Lungs
- Cough, SOB, chest pain, wheezing and laryngitis with mild exposure
- Hypoxia, chemical pneumonia, hemorrhage with moderate to severe exposures

**Notes:**
Eyes:  Initially, ammonia causes burning, tearing, and severe pain.  It has a tremendous capacity to penetrate the eye, causing corneal opacification and lens damage leading to cataract formation. 
Lungs:  Mild exposure causes cough, shortness of breath, chest pain, wheezing, and laryngitis.  Higher exposure can cause hypoxia, chemical pneumonia (pneumonitis), and hemorrhage.  This will gradually improve over 72 hours.  If the patient survives the first 24 hours, recovery is probable.

## Ammonia - Clinical Signs (cont’d)

- Skin
- Pain, blister formation, deep burns
- Gastrointestinal (ingestion)
- Severe mouth pain, cough, abdominal pain
- Nausea and vomiting
- Edema to lips and mouth (leading to airway obstruction)
- Esophageal strictures and perforation

**Notes:**
Skin:  Pain, blister formation, and possibly deep burns similar to frostbite can occur.
Gastrointestinal:  If ammonia is ingested, severe mouth pain, cough, abdominal pain, nausea, and vomiting can occur.  Severe edema of lips and mouth is seen.  The patient should be examined to make certain that laryngeal irritation does not cause airway obstruction.  Esophageal stricture and perforation is common.

## Ammonia - Treatment

- Remove from the exposure
- Decontaminate in field prior to transport
- Irrigate eyes (Morgan lens)
- Early intubation (if inhaled)

**IMAGE:  DOE**

**Notes:**
After the patient has been removed from the area of exposure, decontamination should be started immediately in the field.  Remove all clothing and wash with soap and large amounts of water for 15 to 20 minutes.  Cover burns with a sterile dressing.  The eyes should be irrigated continuously with water.  A Morgan-lens device and topical analgesics will enable continuous eye irrigation therapy.  Both of these items should be considered part of an antidote/equipment cache.  Slit lamp exam after fluorescein staining will reveal the ocular injury.
Damage to the lungs is common after inhaling anhydrous ammonia, often resulting in non-cardiogenic pulmonary edema.  The victims may quickly develop shortness of breath and laryngeal swelling, so early intubation should be considered to protect the airway.

## Chlorine

- Significant irritant to the eyes and respiratory tract
- Characteristic pungent odor
- Used in swimming pools and laboratories
- Industrial exposures produce large number of casualties

**IMAGE:  EPA**

**Notes:**
Chlorine is a significant irritant to the eyes and respiratory tract.  It is widely used in the manufacture of chemicals, plastics, and paper and is commonly used in swimming pools and laboratories.  Industrial exposures have produced large numbers of injuries. The image above shows an uncontrolled chlorine leak resulting from a train derailment in Graniteville, SC in 2005.  The incident released more than 11,000 gallons of chlorine resulting in 9 deaths, caused more than 500 nearby residents to seek medical treatment, and forced the evacuation of more than 5,000. 

## Chlorine - Characteristics

- Properties
- Greenish-yellow gas
- Less alkaline than ammonia
- Chlorine + water = Hydrochloric acid + Free oxygen radicals
- 30x more irritating to lungs than hydrochloric acid
- Effects
- Eye irritation, cough, SOB, wheezing
- 12 to 24 hours, non-cardiogenic pulmonary edema
- Sudden death due to hypoxia

**Notes:**
Characteristics:  Chlorine is a greenish-yellow gas that has a characteristic pungent odor that is irritating to the nasal mucosa.  It is transported as a liquid and is less alkaline than ammonia.
Toxicity:  Chlorine injures cells by reacting with water, producing hydrochloric acid (irritating) and free oxygen radicals (attack cells).  It is toxic to any body surface including the eyes, skin, respiratory tract, and GI tract.  Chlorine gas is 30 times more irritating to the respiratory mucosa than HCl.
In seconds after the exposure, there are symptoms of irritation to the eyes, nose, and throat.  This is followed by irritation of the respiratory tract with coughing, shortness of breath, wheezing, chest pain, and sputum production.  Initial respiratory distress is followed in 12 to 24 hours by a noncardiogenic pulmonary edema.  Sudden death is usually due to severe hypoxia and cardiac arrest.

## Chlorine - Treatment

- Remove from source of exposure
- ABCs
- Flush skin & eyes with water
- Administer oxygen, cool mist, bronchodilators
- Airway management (intubation, Positive End Expiratory Pressure  [PEEP] management)
- Hydration

**IMAGE:  SAIC**

**Notes:**
Treatment:  Move exposed victims away from the source of exposure.  If the victim has no complaints, probably no treatment will be necessary.
Toxicity to skin and eyes should be treated with copious flushing with water.  Irritation of the respiratory tract is treated with oxygen, cool mist to moisten the damaged mucosa, and bronchodilators to resolve bronchospasm.
Intubation, mechanical ventilation, and assessment of hydration may be required.  Bronchoscopy may be useful to remove mucosal plugs.

## Riot Control Agents

- Irritating agents, lacrimators, or “tear gas”
- Eye, nose, mouth, lung irritation
- Widely used as self-protection
- Effects last about 30 minutes

**IMAGE:  USCG**

**Notes:**
Irritating agents, lacrimators (chemicals that stimulate lacrimal glands to produce tears), riot control agents, and tear gas are synonyms for a group of aerosol-dispersed chemicals that 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.  It is widely used in the civilian arena for self-protection.  The deleterious effect is usually transient (about 30 minutes after exposure).
Riot control agents are solids.  They are sometimes dispersed in a solution that is aerosolized and can be dispersed from grenade or bomb.  Some police SWAT teams have small grenades that contain rubber pellets and/or CS.  CN (the active ingredient in Mace®) has caused several deaths from pulmonary injury.  CS is less toxic.  Capsicum, or pepper spray, is derived from the oleoresin capsicum in certain peppers.  It is also used as an over-the-counter topical pain medication.
The Coast Guard volunteer above demonstrates the ocular effects of exposure to OC, or pepper spray.

INSTRUCTOR NOTE:  Though the signs and symptoms related to riot control agents are generally temporary, exposure to high levels of the chemicals or exposure of agent to a patient with underlying respiratory illness can result in more serious illness.

## Riot Control Agents

- CN (Mace)
- CS (tear gas)
- OC (oleoresin capsicum, capsaicin, pepper spray)
- DM (adamsite)

**IMAGE:  SAIC**

**Notes:**
Riot Control Agents include:
  CN (Mace®)
  CS (tear gas)
  OC (oleoresin capsicum or pepper spray)
Adamsite is commonly known as “vomiting” agent.  The onset of its effects is delayed for three to four minutes compared to seconds for CN and CS with symptoms usually resolving in 15 to 30 minutes once removed from the agent environment.

## Riot Control Agents

- Medical management
- Most victims will not seek medical care
- Most effects over in 30 minutes
- < 1% will need care of physician
- Patients seeking care _**MUST**_ be decontaminated - high potential of cross-contamination
- Skin:  soap and cool water
- Eye irrigation
- Lungs:  bronchodilators, oxygen

**IMAGE:  SAIC**

**Notes:**
Medical Management
The effects of the riot control agents will rarely last longer than 30 minutes, although the skin redness or erythema may last longer.  In fact, most people will not seek medical care.  Less than 1 percent will have eye, airway, or skin complaints severe enough to be medically assessed.  A higher percentage might seek care because of anxiety and panic.
There is no antidote available for these agents.  Treatment is supportive and directed towards alleviating symptoms which are not usually severe.
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 ophthalmologist is recommended.
Lungs:  Treat wheezing with bronchodilators or steroids if standard bronchodilators fail.  Oxygen therapy if indicated.  Most symptoms should be maximal within an hour or two.
Skin:  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.  The delayed onset dermatitis should be managed with frequent irrigation and soothing ointments or creams.

## Chemical Weapons Key Points

- _Agent__	__Effects__	__	__	__	__Onset_
- Nerve	Vapor: miosis, 		 	Seconds 		rhinorrhea, dyspnea
- 		Liquid: SLUDGE			Minutes		Both: seizures, apnea 		to hours
- Pulmonary 	Dyspnea, coughing			Hours

**Notes:**
Key signs and symptoms and their onset times.

## Chemical Weapons Key Points

- _Agent__	__Effects__	__Onset_
- Vesicants	Erythema, blisters, 	Hours 		eye irritation, cough, 				dyspnea
- 		(immediately after Lewisite)
- Cyanide	Loss of consciousness, 	 Seconds 	  	convulsions, apnea

**Notes:**
Additional signs and symptoms as well as time of onset for several agents.

## Summary

- Safe medical response to any hazardous materials incident
- Development and implementation of
- Local resources, protocols, policies
- ABCs, antidotes, decontamination
- Exercises, equipment
- Integration of multi-agency planning and training

**Notes:**
To safely respond to a chemical terrorist attack, local communities must develop resources, protocols, and policies that will enable  a safe and appropriate response.  Patients exposed to hazardous chemicals require evacuation, life-saving intervention (ABCs), antidote therapy if available, and decontamination.  First responders and medical personnel must be trained and equipped to safely function in a chemically contaminated environment.
There are a number of chemicals that can cause serious injury to victims.  This lecture has assembled a few of the most common irritants and potentially lethal liquids, gases, and solids that might be used by a terrorist.
Community planning requires multi-agency education and exercises.  Contact the local emergency manager, law enforcement, fire, and EMS leadership to arrange community-wide drills.  Develop a regional and a statewide network that can assist in the event of an attack.

## Questions

- ?

**Notes:**
Questions regarding the chemical agents section?