Transcript HRSA BTCDP Site Visit 2/25/04

New Jersey Preparedness
Training Consortium
Continuing Education
for health care professionals
“modulechemv1”
Chemical Agents of Terror
Background: Recent Chemical
Warfare Agents Terrorist Events
• 1993 World Trade Center Bombing
– Explosive used contained sufficient cyanide to
contaminate entire bldg.
– Cyanide destroyed in blast
• 1995 Aum Shinrikyo sect released Sarin
vapor into Tokyo Subway
– 12 deaths, 5,500 casualties (4,000 w/o clinical
manifestation of injury)
Background (continued)
• Sarin gas was released in the Tokyo subway
system by the Aum Shinrikyo Cult, creating more
than 5,000 victims and causing 12 deaths.
• The same cult had released sarin in an
apartment complex in Matsumoto in 1994, killing
seven and injuring more than 600 people.
• In Tokyo, sarin was concealed in lunch boxes
and bags. The terrorists punctured the bags
with umbrellas and ran out of the
subway tunnel.
Background (continued)
• Iraq reportedly used tabun and maybe
sarin in the Iran-Iraq war (1984–1988).
• Iranian soldiers had atropine autoinjectors.
• Many had atropine overdoses from misuse
of their auto-injectors.
Preparing public health
agencies for chemical attacks
• Enhance epidemiologic capacity for detecting
and responding to chemical attacks.
• Enhance awareness of chemical terrorism
among emergency medical service personnel,
police officers, firefighters, physicians, and
nurses.
• Stockpile chemical antidotes.
• Develop and provide means to detect and
diagnosis chemical injuries.
• Prepare educational materials to inform the
public during and after a chemical attack
Chemical agents
• Range from warfare agents to toxic chemicals
commonly used in industry.
• Criteria for determining priority chemical agents
include
– chemical agents already known to be used as
weaponry
– availability of chemical agents to potential terrorists
– chemical agents likely to cause major morbidity or
mortality
– potential of agents for causing public panic and social
disruption
– agents that require special action for public health
Source CDC
preparedness
Potential Terrorism Risks from
Chemical Warfare Agents
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Detonation of CWA-containing munitions
Atmospheric Dispersal
Contamination of Food Supplies
Contamination of Water Supplies
Product Tampering
Low Probability/High Consequence Event
Sources of CW Agents
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Foreign governments
Internet recipes
Crime and corruption in former Soviet Union
U.S. Chemical plants (e.g. Cl, Phosgene, etc)
U.S. Military Stockpile
– (est. 30,600 tons of nerve agents and vesicant at 8
sites across U.S.)
– 1985 law directed DoD destroy stockpile by 1994
…extended to 2004)
• U.S. Military non-stockpile
– (outdated CWA and recovered weapons…buried at
215 sites)
Sources (continued)
• The United States has over 30,000 tons of VX
and sarin.
• The government is planning the destruction of
this stock and has already destroyed small
batches.
• Dupont Chemical is negotiating for the contract
to destroy 1,200 tons of VX stored in the
Newport chemical depot.
• There is an ongoing discussion about the best
way to dispose of the end products.
CWA Characteristics
• Volatility
– Tendency to evaporate from liquid to gas form
– Greater volatility= shorter persistence
• Vapor Density
– Weight of the vapor or mist relative to air
– All CWA’s (except HCN) heavier than air
• Persistence
– Most evaporate > 24 hours
– Present increased risk for skin exposure to victims
and risk to responders
Toxicity of CWA’s
• Potential to cause injury in biologic systems
– LD50 – single dose causing death in 50% of animals
– ED50 – dose where 50% of exposed population will
exhibit signs or symptoms
– LD50 and ED50 limited use for toxicity of agents
inhaled or absorbed across mucous membranes
– Concentration-time (Ct) used for CW Agents
• Concentration in air x time exposed
• Represented as milligrams/minute/cubic meter
• Latency – time delay between exposure and
clinical signs/symptoms (sulfur mustard and
pulmonary have longest…nerve agents and
cyanides shortest)
Clues suggesting release of a
chemical agent
• An unusual increase in the number of patients
seeking care for potential chemical-release-related illness;
• Unexplained deaths among young or healthy
persons
• Emission of unexplained odors by patients
• Clusters of illness in persons who have common
characteristics, such as drinking water from the
same source
• Rapid onset of symptoms after an exposure to a
potentially contaminated medium (e.g.,
paresthesias and vomiting within minutes of
Clues suggesting release of a
chemical agent
• Unexplained death of plants, fish, or
animals (domestic or wild)
• Syndrome (i.e., a constellation of clinical
signs and symptoms in patients)
suggesting a disease associated
commonly with a known chemical
exposure (e.g., neurologic signs or
pinpoint pupils in eyes of patients with a
gastroenteritis-like syndrome or acidosis in
patients with altered mental status).
Classes of Chemical Agents
• Nerve Agents
– Inhibit acetylcholinesterase (AChE) causing Ach
accumulation and excessive cholinergic stimulation
• Incapacitating Agents
– Irritation and extreme pain to affected organs
• Pulmonary Agents
– Impair ability to function- not permanent
• Lacrimators, sternutators, vomiting
• Vesicants/Blistering/Vomiting Agents
– Extensive irreversible tissue damage
• Blood Agents
– Interfere with cellular respiration
General Treatment Guidelines
• Nerve Agents
– Atropine, pralidoxime chloride (2-PAMCl), or
diazepam
• Incapacitating Agents
– Remove to fresh air, decon w/water, 6% bicarbonate
solution
• Pulmonary Agents
– Supplemental oxygen, restrict physical activity,
medical attention
• Vessicants/Blister Agents
– Remove to fresh air, remove clothing, decontaminate
skin, supplemental oxygen, hospitalization, extensive
irrigation of eyes
• Blood Agents
– Amyl nitrate, sodium nitrate, sodiumthiosulfate
Patient Management and
Treatment
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Focus on Airway, Breathing, Circulation (ABCs)
Personal Protective Equipment (resp, skin)
Clothing Removal
Decontamination of Patient
Copious water w/any liquid soap
0.5-2% bleach solution (controversial)
Soft sponges (no abrasive cleaners)
Plain water or normal saline for eyes
Do not delay irrigation
Chemical Warfare Agent Detection
• Ionization Instruments
– Flame Ionization Detectors (FID)
• Poor range of detection
• Not selective
– Photo Ionization Detectors (PID)
• Good range of detection
• Not Selective
Chemical Warfare Agent Detection
• Ionization Instruments
– Ion Mobility Spectrometry (IMS)
• Excellent range of detection
• Moderately selective
Chemical Warfare Agent Detection
• Surface Acoustic
Wave (SAW)
– Very Good range of
detection
– Fairly Selective
• Filter Based Infrared
Spectroscopy(FBIS);
or Non-Dispersive
Infrared (NDIR)
– Very Good range of
detection
– Fairly Selective
Chemical Warfare Agent Detection
• Colorimetric Tubes
– Very good range of detection
– Fairly Selective
• Electrochemical Sensors
– Poor range of detection
Nerve Agents
Nerve
• Tabun (GA)
• Sarin (GB)
• Soman(GD)
• Cyclosarin (GF)
• VE
• VG
• V-Gas
• VM
• VX
Health Effects of Nerve Agents
• Toxic by inhalation, absorption or ingestion in
very small amounts
• Effects after dermal exposure may be delayed
for as long as 18 hours.
• Effects - runny nose, chest tightness, pinpoint
pupils, shortness of breath, excessive salivation
and sweating, nausea, vomiting, abdominal
cramps, involuntary defecation and urination,
muscle twitching, confusion, seizures, paralysis,
coma, respiratory paralysis, and death.
Nerve Agents
• Incapacitating effects occur within 1 to 10
minutes and fatal effects can occur within 1 to 10
minutes for GA, GB, and GD, and within 4 to 42
hours for VX.
• Fatigue, irritability, nervousness, and memory
defects may persist for as long as 6 weeks after
recovery from an exposure episode.
• We do not know if exposure to the nerve agents
GA, GB, GD, or VX might result in reproductive
effects in humans.
• Source: ATSDR
Nerve Agents
• “Nerve agents” are aptly named, since
they affect the nervous system.
• Structural name for these agents is
organic phosphorous compounds (OPCs)
• Term “nerve agents” commonly used to
refer to a specific military class of OPCs
– soman, sarin, tabun, VX
Nerve Agents
• In fact, the OPCs also include several hundred
“nonmilitary” OPCs.
– Malathion
– Parathion
– Others
• Used commonly as insecticides, where military
OPCs are used to kill humans
• Both can kill humans, just differently
• Nerve agents are used in the treatment of
myasthenia gravis and anticholinergic drug
poisoning
Physical Properties
• Liquids with varying volatility and
persistence
• VX is the least volatile but the most
persistent; “oily.” Soman is odorless.
• Tabun, sarin, and soman have significant
volatility. Sarin is the most volatile.
• Absorbed via skin, mucus membranes,
lungs, and gastrointestinal system.
Toxicity
• Dermal toxicity: One drop of VX,1–10 ml of
the G agents may be fatal.
• Onset of symptoms may be delayed
several hours from exposure to the liquid
form, especially VX (up to 18 hours).
• Rapid development of symptoms after
exposure is more likely.
Lethality of VX
• An amount of VX
equal in size to one
column of the building
depicted on the back
of this penny would
be lethal.
Mechanism of Action
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Nerve agents bind and inhibit acetylcholine
esterases.
Acetylcholine esterase breaks down
acetylcholine (ACh).
ACh mediates neurotransmission at
 nicotinic muscular junctions,
 autonomic nicotinic synaptic junctions (sympathetic
and parasympathetic), and
 muscarinic end-organ synapses (GI tract, glands,
bladder, pupils).
Autonomic Nervous System
Parasympathetic
Autonomic
Ganglia
N
ACh
N
ACh
Somatic
Central
Sympathetic
N
ACh
N
ACh
M
ACh
End
Organ
Glands
Bladder
Gut
Heart
M
ACh
M
A
A
N
ACh Epinephrine Norepinephrine
Sweat Glands
Heart
Blood Pressure
ACh
Neuromuscular
Junction
Brain
Mechanism of Action (continued)
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Enzyme inhibition is reversible within a certain
period of time that is agent dependent.
This time period in which structural changes to
the enzyme occur is called “aging.”
Soman ages within minutes, whereas sarin
takes hours.
After aging occurs, the enzyme is inactivated.
Enzyme regeneration usually takes several
weeks.
Excess ACh at all these synapses accounts for
the clinical presentation.
Clinical Presentation
Muscarinic:
SLUDGE—
Salivation
Lacrimation
Urination
Diaphoresis
GI distress (diarrhea, vomiting)
Emesis
Miosis
BBBs—
Bradycardia
Bronchorrhea
Bronchospasm
Clinical Presentation (continued)
• Nicotinic: MTWThF
– Mydriasis
– Tachycardia
– Weakness
– Hyperthermia
– Fasciculation
Clinical Presentation (continued)
• Military class OPCs (sarin, soman, etc.)
– Preferential affinity for nicotinic receptors
• Muscle paralysis
• Effective battlefield weapon
• Insecticide class OPCs (malathion)
– Preferential affinity for muscarinic receptors
• SLUDGE
• BBBs
Clinical Presentation (continued)
• Dim vision and eye pain from ciliary spasm
or direct cortical effect?
• Cardiovascular effects are less predictable
and range from bradycardia with AV blocks
to tachycardia.
Clinical Presentation (continued)
• Compared with adults, children exposed to nerve agents
are thought to be less likely to have miosis and more
likely to have increased secretions.
• Children are also thought to have more seizures,
hypotonia, and weakness than adults.
• No studies have been done on nerve agents and
children, even though historical incidents have affected
children.
• Assumptions about children and nerve agents are based
on knowledge of organophosphates and of
characteristics of children such as lower weight, less
active metabolism (paroxanase activity), and greater
ventilatory rate.
Differential Diagnosis for Nerve
Agent Poisoning
• Gastroenteritis
• Ingestion of muscarinic mushrooms
(Amanita muscaria, Clytocybe, Inocybe)
• Pesticide poisoning
• Carbamate overdose
• Metal ingestion
Diagnostic Workup
• No lab workup is useful for acute nerve
agent poisoning.
• RBC and plasma cholinesterase
(butylcholinesterase) levels may be
checked. These results are usually not
immediately available.
Prehospital Care and
Decontamination
• First responders: Respirators, goggles,
protective clothing
• Self-contained breathing apparatus (SCBA) is
recommended in response to any nerve agent
vapor or liquid.
• Butyl rubber gloves (most agents are lipophilic)
• 20% of healthcare workers in Tokyo had mild
symptoms after taking care of patients. These
symptoms included nausea, eye pain, and
headache.
Prehospital Care and
Decontamination (continued)
• Inhalation exposure: removal from
exposure
• Dermal: wash with soap and water or mild
(0.5%) sodium hypochlorite (bleach)
solution if availability of water is limited
• Ingestion: no charcoal as these patients
are at risk for vomiting and aspiration
Antidotes: Atropine
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Muscarinic receptor antagonist.
Only treats muscarinic symptoms.
Given IV, IM, or by ET tube.
Dose is 2 mg every 5–10 minutes. End point is resolution
of bronchorrhea.
• For children, give 0.5–1.0 mg IM/IV every 5–20 minutes.
For children < 6 months old, the dose is 0.05 mg/kg, with
the minimum dose being 0.1 mg. Same end point.
• If given early, atropine may prevent seizures.
• Glycopyrrolate may also be used but does not penetrate
the CNS.
Antidotes: Oximes
• Reverses the binding of the nerve agent to the
enzyme, especially if given prior to aging. Also
acts as a scavenger and inactivates circulating
nerve agents.
• Pralidoxime: Slow IV bolus. Dose is 25–
50 mg/kg in children or 2 g in adults, targeting a
serum level of > 4 mg/L. If given IM using the
auto-injector, level is achieved in 8 minutes.
• May repeat dose in 1 h. Effect is lost after 3 h of
exposure to sarin because of aging.
Antidotes: Oximes (continued)
• Side effect: elevated BP and EKG
abnormalities
• Other oximes (such as obidoxime and
P2S) are used in other countries and have
variable efficacy.
• There is ongoing research to develop
better agents.
Antidotes: Benzodiazepines
• Used to treat the seizures
• Diazepam IM/IV appears to be better than
other benzodiazepines.
• Dose is 5 mg IV/IM. May be repeated
every 5–15 minutes.
Antidotes: Pyridostygmine
• Subjects pretreated with pyridostigmine will be
less vulnerable to nerve agents.
• The U.S Army used pyridostigmine during the
Gulf War.
• Pyridostigmine is a carbamate that binds
reversibly to AChE. It does not cross the CNS.
• Pretreated individuals will have a store of AChE
that is bound to pyridostigmine and is protected
from the nerve agent.
Antidotes: Pyridostygmine
(continued)
• Bound pyridostigmine-AChE
spontaneously breaks after several hours,
releasing normal AChE. Administration of
2-PAM stimulates release of AChE that
was protected from the nerve agent by
pyridostigmine.
Antidotes: Pyridostigmine
Antidotes: MARK I Kit
• Contains pralidoxime
(600 mg) and atropine
(2 mg) self injectors
Psychological Impact
• Psychological impact has been seen after
exposure to nerve agents as well as other
terrorist attacks.
• Post traumatic stress disorder seen in 60% of
victims of the Tokyo sarin gas attack at
6 months.
• Fear of riding the subway, nightmares, and
depression were some of the common
symptoms (Kawana N, Ishimatsu S, Kanda K.
Psycho-physiological effects of the terrorist sarin
attack on the Tokyo subway system. Military
Medicine 166(12 Suppl):23–6, 2001 Dec.).
Experimental Therapies for Nerve
Agent Exposure
• Exogenous choline esterases to bind the nerve
agents
• Paroxinases that degrade the nerve agents
• Hl-6 thought to work better than pralidoxime for
exposure to soman, which ages quickly. HI-6
has been shown to work when it is administered
to rats up to 2 hours before exposure (Kassa J,
Fusek J. The influence of oxime selection on the
efficacy of antidotal treatment of somanpoisoned rats. Acta Medica 45(1):19–27, 2002).
Incapacitating Agents
Riot Control/Tear
• Bromobenzylcyanide
Chloroacetophenone
• Chloropicrin
• CNB - (CN in
Benzene and Carbon
Tetrachloride)
• CNC - (CN in
Chloroform)
• CNS - (CN and
Chloropicrin in
Chloroform)
Vomiting
• Adamsite (DM)
• Diphenylchloroarsine
(DA)
• Diphenylcyanoarsine
(DC)
Other
• Agent 15
• BZ
• Canniboids
• Fentanyls
• LSD
• Phenothiazines
Health Effects of Incapacitating
Agents
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Short Duration of Action
Irritation and extreme pain
Eyes, nose, respiratory tract
Occasionally vomiting follows exposure
Sometimes esophageal or laryngeal
constriction
• Hallucinogenic
Choking/Lung/Pulmonary
Damaging Agents
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Chlorine (CL)
Diphosgene (DP)
Cyanide
Nitrogen Oxide (NO)
Perflurorisobutylene (PHIB)
Phosgene (CG)
Red Phosphorous (RP)
Sulfur Trioxide-Chlorosulfonic Acid (FS)
Teflon and Perflurorisobutylene (PHIB)
Titanium Tetrachloride (FM)
Zinc Oxide (HC)
Health Effects of Pulmonary
Agents
• Inhalation primary route of entry
• Variety of upper respiratory and pulmonary
effects
• Variable latency (water solubility impacts) from
minutes to 72 hours
• Latency decreased with length of exposure and
physical activity
• Shallow breathing, chest tightness, cough
• Laryngeal spasm, airway obstruction, pulmonary
edema (2-6 hours post exposure)
Blister/Vesicants
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Distilled Mustard (HD)
Lewisite (L)
Mustard Gas (H) (Sulfur Mustard)
Nitrogen Mustard (HN-2)
Phosgene Oxime (CX)
Ethyldichloroarsine (ED)
Methyldichloroarsine (MD)
Mustard/Lewisite (HL)
Mustard (H)
Acute Effects of sulfur mustard
exposure
• 5% Fatality. Low or no garlic like odor.
• Symptoms delayed 2 to 24 hours.
• Skin: redness and itching of the skin may occur
2 to 48 hours after exposure and change
eventually to yellow blistering of the skin.
• Eyes: irritation, pain, swelling, and tearing may
occur within 3 to 12 hours of a mild to moderate
exposure. A severe exposure may cause
symptoms within 1 to 2 hours and may include
the symptoms of a mild or moderate exposure
plus light sensitivity, severe pain, or blindness
(lasting up to 10 days).
Acute Effects of sulfur mustard
exposure
• Respiratory tract: runny nose, sneezing,
hoarseness, bloody nose, sinus pain,
shortness of breath, and cough within 12
to 24 hours of a mild exposure and within
2 to 4 hours of a severe exposure.
• Digestive tract: abdominal pain, diarrhea,
fever, nausea, and vomiting.
Chronic Effects of Mustard
• Exposure to sulfur mustard liquid is more likely
to produce second- and third- degree burns and
later scarring than is exposure to sulfur mustard
vapor. Extensive skin burning can be fatal.
• Extensive breathing in of the vapors can cause
chronic respiratory disease, repeated respiratory
infections, or death.
• Extensive eye exposure can cause permanent
blindness.
• Exposure to sulfur mustard may increase a
person’s risk for lung and respiratory cancer.
Blood Agents
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Arsine (SA)
Cyanogen Chloride (CK)
Hydrogen Chloride
Hydrogen Cyanide (AC)
Health Effects of Blood Agents
• Immediate signs and symptoms of cyanide
exposure
• Rapid breathing
• Restlessness
• Dizziness
• Weakness
• Headache
• Nausea and vomiting
• Rapid heart rate
Health Effects of Blood Agents
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Convulsions
Low blood pressure
Slow heart rate
Loss of consciousness
Lung injury
Respiratory failure leading to death
Survivors of serious cyanide poisoning may
develop heart and brain damage.
Sources of Information
www.bt.cdc.gov/agent/agentlistchem-category.asp
Helpful Resources
• http://www.bt.cdc.gov/agent
• NJ Poison Information and Education 1-800-222-1222
• Medical Management of Chemical Casualties Handbook
(http://www.fas.org/nuke/guide/usa/doctrine/army/mmcch
/NervAgnt.htm)
• CDC. Case Definitions for Chemical Poisoning. MMWR
Recommendations and Reports, January 14, 2005,
54:RR-1. Available at www.cdc.gov and at www.njptc.org
• To obtain emergency information from CDC, 1-770-4887100