Transcript Chemical Terrorism

Chemical Terrorism
Amita Shroff, MD
June 10, 2010
Chemical Terrorism - Background
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Dates back many years
First use: World War I
Modern use of chemical terrorism
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Cyanide: Chicago, Illinois – 1984
Sarin :Tokyo, Japan-1995
Carbamate Insecticide: Fresno, California – 1999
Nicotine: Grand Rapids, Michigan – 2002
QUESTION 1
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Reports of an unknown Chemical Substance have been
released during an outdoor family concert. Participants
arrive to the ED with C/O copious oral/nasal secretions,
labored breathing, and muscle fasciculation. What othre
PE finding should you expect?
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A. Dry Skin
B. Miosis
C. Normal Mental Status
D. Constipation
E. Hypotension
QUESTION 2
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Group of boy scouts present to ED. They were hiking
and encountered an oily, dark brown liquid with a
mustard odor. They had erythema and blisters of the
leg. Some have eye irritation and SOB. Which would be
helpful in treating these patients
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A. Supportive care only
B. Atropine and 2-PAM
C. Sodium Nitrite
D. Midazolam
E. Ciprofloxacin
QUESTION 3
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Terrorist release a chemical in a school with an odor of
newly mown hay. Few hrs later, students start
complaining of ocular and nasal irritation followed by DIB
and cough. Those seen in ED have CXR with
pulmonary edema. Most likely chemical of use is:
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A. Phosgene
B. Sarin
C. Cyanide
D. Lewisite
E.Mase
QUESTION 4
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A foreign diplomat’s 12 yr son presents to the ED with
C/O headache and nausea. He soon develops severe
dyspnea and cyanosis. As he is moved into the trauma
bay, he starts to seize. You suspect he has been
exposed to:
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A. Soman
B. Cyanide
C. Sulfur Mustard
D. Phosgene
E. 1-Chloroacetophenone
QUESTION 5
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Terrorist have released a chemical in a school bus full of
children across the street from the hospital. In
preparation for decon, HOSPITAL PERSONNEL should
don what type of PPE?
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A. Self –containing breathing apparatus (SCBA), fully
encapsulating chemical protective suit
B. SCBA, chemical resistant clothing
C. Full face air purifying respirator, chemical resistant clothing
D. Coveralls and safety shoes/boots
E. Gown and gloves
Chemical Terrorism - Background
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Apocalyptic groups
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Aum Shinrikyo, Japan (1995)
Restoration of the 10 Commandments, Uganda
(2000)
Political groups
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Hamas/Hizbollah, Middle East (2000-present)
Western Group of Federal Forces, Chechnya
(2000)
Revolutionary Armed Forces of Colombia (2001)
Al Qa’ida (2001-present)
1995: Nerve gas attack on Tokyo
subway
1995: Nerve gas attack on Tokyo subway
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Aum Shinrikyo converge at Kasumigaseki subway
station
Release lethal sarin gas
Terrorists take sarin antidote and escaped
Commuters, blinded and gasping for air, rushed to the
exits
Twelve people died, over 5,000 were treated in hospitals
(many comatose state)
Japanese police raided Aum Shinrikyo headquarters
Arrested hundreds of members, including: Master Shoko
Asahara.
1995: Nerve gas attack on Tokyo subway
Master Shoko Asahara (Cult Leader)
Chemical Terrorism - Effects
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Toxic effects:
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Topical injury
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Skin
Eyes
Mucous membranes of respiratory tract
Systemic absorption
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Dermal
Respiratory
Chemical Terrorism - Treatment
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General treatment of contaminated victims:
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Triage
Emergent resuscitation
Decontamination if needed
Airway / cardiopulmonary support
Emergent antidotal therapy
Decontamination
Chemical Terrorism - Decontamination
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Decontamination
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Appropriate level PPE required (hot zone)
Field / Special designated area outside the ED
Simple disrobement: removes ≥ 80-90%
Irrigation with soap and tepid water
0.5% sodium hypochlorite (adults)
Pediatrics Considerations:
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Warmer water (>37.8C)
Low pressure systems
Chemical Terrorism - Decontamination
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Vapor exposure: clothing removal and hairwashing (sufficient)
Liquid dermal exposure: thorough
decontamination necessary
Ocular exposure: copious irrigation
Chemical Terrorism - PPE
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Level A
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Highest level of protection
Highly contaminated area (hot zone)
Self contained breathing apparatus (SCBA)
Fully encapsulated suit
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Slightly pressurized
Chemical resistant gloves
Hot, bulky and clumsy
Chemical Terrorism - PPE
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Level B
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Lower level than A
Respiratory protection, less skin protection
Outside hot zone / partially decontaminated pts
SCBA
Non-pressurized suit
Butyl rubber gloves/boots
Hot, bulky and clumsy
Chemical Terrorism - PPE
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Level C
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Lower than Levels A & B
Contaminants have been identified (low [ ])
Air-purifying respirator: sufficient
Some protection against skin contact
Equipment: easier to work with
Chemical Terrorism - Agents
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Nerve agents
Vesicants
Pulmonary agents (irritant gases)
Riot control agents
Incapacitating agents
Cyanide
Nerve Agents
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Highly toxic
Organophosphate insecticides (signs and
symptoms)
Powerful inhibitors of acetylcholinesterase
(AChE)
Acetylcholine accumulation → abnormal
neurotransmission
Nerve Agents
Breakdown of
Acetylcholine
Acetylcholine
accumulation
AchE inhibited by nerve agent →Acetylcholine accumulation → Abnl neurotransmission
Nerve Agents – Clinical Sx’s
Cholinergic Syndrome
Central
Nicotinic
Neuromuscular junction
Sympathetic ganglion
Altered mental status →
lethargy → coma, ataxia,
convulsions and respiratory
depression
Muscle fasciculation and
twitching → weakness → flaccid
paralysis
Tachycardia, hypertension and
metabolic abnormalities (↑
glucose, ↓ K+, and acidosis)
Nerve Agents – Clinical Sx’s
Cholinergic Syndrome
Muscarinic (parasympathetic)
Smooth muscle
Exocrine gland
Ocular: miosis, visual blurring,
and lacrimation
Respiratory: rhinorrhea,
bronchospasm and ↑ bronchial
secretions (cough, wheezing,
and dyspnea)
CV: bradycardia, hypotension
and AV block
Dermal: flushing + sweating
GI: salivation, N/V, diarrhea
and abdominal cramps
GU: frequency, urgency and
incontinence
Nerve Agents
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Onset and type of symptoms depends:
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Concentration
Route of exposure
Vital sign abnormalities:
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Sympathetic ganglia
Parasympathetic ganglia
Nerve Agents - Exposure
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Low doses:
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High doses:
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Respiratory effects
Severe exposure:
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Miosis
Cojunctival injection
Pain
Rhinorrhea
Neurologic findings
Death:
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Respiratory depression and apnea
Nerve Agents - Exposure
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Vapor exposure (triad):
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Ocular
Nasal
Respiratory
Dermal exposure (progression):
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Localized sweating and fasciculations → nausea,
vomiting , diarrhea and fatigue
Severe exposure → respiratory and neurologic
symptoms
Nerve Agents
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Children:
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Less likely: miosis and peripheral
parasympathetic effects
More likely: CNS depression, hypotonia,
weakness and seizures
Animal studies: children only need 10-33% of
lethal dose on an equivalent mg/kg basis
Nerve Agents - Examples
Agent
Odor
Sarin (most volatile)
Odorless
Venom X [VX] (most
potent / persistent)
Odorless
Tabun
Fruity
Soman
Fruity/Camphorous
1995: Sarin episode in Tokyo
Nerve Agents - Management
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Self protection / PPE (contamination HIGH)
Agents readily absorbed
Patient decontamination:
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Warm water / soap
? Diluted bleach solution (adults)
Nerve Agents - Management
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Restoring ventilation and oxygenation
Aggressive use of antidotes
Cardiac monitoring: dysrhythmias (torsades)
Benzodiazepines – neuroprotective
Close observation
Nerve Agents - Antidote
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Atropine
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.05 -.10 mg/kg IV or IM
 Min 0.1mg, max 5mg
 Repeat Q 2-5 min for secretions
Pralidoxime (2-PAM)
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25-50 mg/kg IV or IM
Max 1 gm
Repeat Q 30-60 min (persistent
weakness)
Nerve Agents - Antidote
Atropine
•Reverses parasympathetic
findings
•Blocks muscarinic receptors
• No effect on motor endplates
• Lacrimation
• Salivation
• Vomiting+diarrhea
• Urination
• Bronchorrhea
• Bronchospasm
• Bradycardia
2-PAM
• Reactivates AChE (nucleophilic • Weakness
attack on agent)
• Fasciculations
• Reverses nicotinic, muscarinic
and CNS effects
Nerve Agents - Antidote
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Military Mark I autoinjector kits:
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2 mg of atropine
600 mg of 2-PAM
Immediate IM use in the field
Stockpile (civilian first responder)
Not approved in pediatrics
Pediatric auto-injector recently approved
Nerve Agents - Aging
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Aging: permanent inhibition of AChE activity
(irreversible covalent binding)
Need early 2-PAM therapy prior to aging
Nerve Agents
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Difference from organophosphate pesticide
poisoning:
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Continuous infusions usually not necessary
(atropine or 2-PAM)
Delayed peripheral neuropathies not seen
Life support + antidotal therapy →prognosis
good
Potential advances in treatment:
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More effective oximes: HI-6
Fetal bovine serum acetylcholinesterase
Vesicants
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Vesicants: agents that produce blistering
Severe dermal manifestation in children
Released as an aerosol
3 primary vesicants:
Sulfur mustard (H and HD)
Lewisite (L)
Phosgene oxime (CX)
Vesicants - Sulfur Mustard
(SM)
Vesicants - Sulfur Mustard
(SM)
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Most viable threat ( ≥ 12 countries have SM
in their arsenals)
Easiest to synthesize
WWI: more casualties then all chemical
agents combined
1980’s: >45,000 casualties in Iran-Iraq war
Vesicants - Sulfur Mustard
(SM)
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Alkylating agent, highly reactive and
electrophilic
Oily liquid with odor of garlic, mustard or
horseradish
LD 50 is approximately 1.5 teaspoons
Clinical effects: dose dependent
Symptoms usually delayed for 4-8 hours
Vesicants - Sulfur Mustard
(SM)
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Symptoms:
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Low doses: vessication
Higher doses: vessication and systemic toxicity
Skin: erythema → blister formation
Ocular: edema, conjunctival injection, corneal
ulceration
Respiratory: cough/hoarseness, tachypnea,
bronchospasm, pulmonary edema
Vesicants - Sulfur Mustard
(SM)
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Systemic absorption involves:
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Hematopoietic
GI
CNS
Expected mortality = 3% for those reaching
medical facility
Children:
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More rapid onset
Worse dermal reactions
Vesicants – Lewisite (L)
Vesicants – Lewisite (L)
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Potency similar to sulfur mustard
Oily, colorless liquid with geranium odor
Released by Japan during wartime
Known stockpiles in Russia
Active ingredient: trivalent arsenic
Inhibits various enzymes and glycolysis
Skin irritation and pain present within 15-30
minutes, blister formation by 2 hours
Vesicants – Lewisite (L)
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Skin lesions:
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less erythema
more tissue destruction then sulfur mustard
lesions
Ocular pain and irritation within minutes
Central airway inflammation and upper
airway irritation
Edema in severe cases
Hypotension and hemolytic anemia rare
Vesicants – Lewisite (L)
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BAL (British anti-Lewisite) or dimercaprol:
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Arsenic chelator
Prevents / decreases severity of skin and eye
lesions if applied within minutes of exposure
Topical form not widely available
IM BAL reduces mortality from systemic effects of
lewisite
Vesicants – Phosgene Oxime (CX)
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Extensive tissue damage
Instantaneous pain and irritation of the skin,
eye and airways
Skin → blanches → turns gray → urticarial,
erythematous and edematous → necrosis /
eschar formation
True vesicle formation DOES NOT occur
Vesicants – Phosgene Oxime (CX)
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Ocular findings similar to lewisite
Pulmonary edema is common and may see
bronchiolitis
Vesicants
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Vesicant toxicity: clinical diagnosis
Urinary thiodiglycol metabolites will confirm
sulfur mustard exposure
Death most frequently occurs 5-10 days after
exposure (pulmonary insufficiency / infection)
Long-term hospitalization expected
Vesicants - Treatments
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PPE for healthcare workers
Immediate decontamination (water and soap)
Only water for phosgene oxime exposure
Dilute hypochlorite solution (adults) – for
water insoluble mustards and lewisites
Vesicants - Treatments
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No antidote
Aggressive airway, fluid, electrolyte and pain
management
? GCSF - mustard induced leukopenia
Infection prevention with antibiotics
Burn center referral
Pulmonary Agents (Irritant Gases)
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Pulmonary agents classified according to
anatomical infliction
Affect central or peripheral pulmonary system
Central: Upper airways (cough or stridor)
Peripheral: lower airways (pulmonary edema)
Pulmonary Agents (Irritant Gases)
Phosgene (CG, carbonyl chloride, DStoff, or green cross)
Chlorine
Nitrogen oxides
Ammonia
Pulmonary Agent - Phosgene
Pulmonary Agents - Phosgene
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Gas with a density 4X that of air
Found in plastics, pharmaceutical and textile
industries
When released:
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forms a white cloud
odor of newly mown hay
Water insoluble
Pulmonary Agents - Phosgene
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Initially asymptomatic with perception of odor
Mild exposure:
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Major toxicity:
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Eyes, nose, throat and upper airway irritation
Acid burn to lower airways
Diffuse capillary leak
Pulmonary edema
Pulmonary edema: delay 4-6 hrs (as late as
24 hrs)
Pulmonary Agents – Phosgene
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Management
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Primarily supportive care
Decontamination: removal of victim to fresh air
Respiratory:
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Pulmonary secretions
Bronchospasm
Pulmonary edema
Aggressive treatment of secondary bacterial
infections
Pulmonary Agents - Phosgene
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Management:
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Steroids: ?severe bronchospasm
Anti-inflammatory agents (NAC/ibuprofen): ?
pulmonary edema
24- hour observation for all asymptomatic patients
Pulmonary Agents - Phosgene
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Poor prognosis: dyspnea or pulmonary
edema within 4 hours
Patients usually survive if symptomatic after 6
hrs and ICU available
Recovery within 3-4 days
Pulmonary Agents - Chlorine
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Widely available
Dense, green-yellow gas with pungent odor
Intermediate water solubility → upper + lower
airways affected
Early inflammatory injury
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Formation of acids and oxidants upon contact
with moist mucous membranes
Pulmonary Agents - Chlorine
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Mild Exposure:
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Immediate ocular, nasal and upper airway
irritation
Nausea and vomiting
Severe Exposure: (sx within 12-24 hrs)
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Coughing and hoarseness
Pulmonary edema
Permanent reactive airway disease (inhalation)
Pulmonary Agents - Chlorine
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Management:
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Supportive care
Humidified oxygen
Bronchodilators
? Nebulized sodium bicarbonate (3.75%) solution
Skin decontamination
Pulmonary Agents-Nitrogen Oxide
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Silo gas:
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Product of fire combustion
Industrial process
Military blast weapons
Limited water solubility
Lower airway toxicity
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Nitrogen oxide converted to nitric acid → alveolar
injury → pulmonary edema
Pulmonary Agents-Nitrogen Oxide
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Triphasic illness:
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Dyspnea and flu-like symptoms
Transient improvement
Pulmonary edema with worsening dyspnea (24-72
hrs)
Other consequences:
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Methemoglobinemia
Bronchiolitis obliterans (late complication)
Pulmonary Agents - Ammonia
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Fertilizer and industrial chemical
Highly water soluble
Colorless, alkaline, corrosive gas
Rapidly reacts with water to form ammonium
hydroxide
Pungent odor
Pulmonary Agents - Ammonia
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Immediate eye, mucous membrane and
throat irritation
Lower airway involvement:
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Bronchospasm
Pulmonary edema
Reactive airway disease
Pulmonary Agents - Ammonia
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Treatment
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Supportive
Humidified oxygen and bronchodilators
Ocular irrigation → evaluation for corneal burns
Riot Control Agents
Riot Control Agents
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Lacrimators or “tear gas”
Significant disruption and panic in crowds
Transient but intense noxious effects
Symptoms resolve within a few hours
Pulmonary edema with large exposure in
confined spaces
Riot Control Agents
CS (0-chlorobenzylidene malonitrile)
CN (1-chloroacetophenone) “mace”
OC (capsaicin) “pepper spray”
Riot Control Agents
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Symptoms
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Immediate irritation of eye and respiratory tract
Blepharospasm
Lacrimation
Coughing, sneezing and rhinorrhea
Burning sensation: exposed skin and mucous
membranes
Nausea, headaches and photophobia
↑ [ ], skin blistering / pulmonary involvement
Riot Control Agents
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Management
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Removal from exposure
Copious ocular irrigation
Skin decontamination
Incapacitating Agents - Military
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Military incapacitating agents: physiologic or
mental effects
Usually not lethal
Recovery: several hours to days
Anticholinergic deliriants (QNB, BZ)
Incapacitating Agents
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Signs and symptoms (Anticholinergic):
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Delirium
Hallucinations
Mydriasis
Tachycardia
Ileus
Dry mucous membranes
Absent axillary sweat
Urinary retention
Hyperthermia
Incapacitating Agents
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Treatment:
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Supportive care
Benzodiazepines to prevent:
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Hyperthermia
Rhabdomyolysis
Physostigmine:
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Refractory seizures
Profound tachycardia
Incapacitating Agents
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Other incapacitation agents: (besides military
agents)
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Stimulants
Potent opioids (carfentanyl, aerosol fentanyl)
Hallucinogens (LSD, Cannabinoids)
Vomiting Agents
Cyanide
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Long term use as a toxin for sinister purposes
Chemical terrorism agent: limited
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volatility in open air
low lethality compared to nerve gas
Devastating effects in a crowded, closed
room
Cyanide
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Toxicity: Interference with normal
mitochondrial oxidation → lactic acidosis
High affinity for ferric iron (Fe3+)
Brain and heart targeted because most
dependent on oxidative phosphorylation
Cyanide
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Clinical presentation: route and dose of
exposure
Inhalation of gas: LOC within seconds
Oral exposure: symptoms from 30 min up to
several hours
“Bitter almond” smell
Cyanide
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Mild exposures:
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Tachypnea and hyperpnea
Tachycardia
Flushing
Dizziness and headaches
Diaphoresis
Nausea and vomiting
Serious exposures:
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Seizures, coma and apnea
Cardiac arrest
Cyanide
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Laboratory findings:
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Cyanide levels (levels > 1.0 mg/L produce
acidosis)
Large anion gap (lactic acidosis)
Venous blood gas: diminished arterial-venous o2
(Ao2-Vo2) difference
EKG changes
Cyanide
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Management:
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Removal of victim to fresh air
Removal of any wet clothing and skin decon
Intensive supportive care
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100% oxygen
Mechanical ventilation
Circulatory support (crystalloids and vasopressors)
Correction of metabolic acidosis (IV NaHCO3)
Benzodiazepines for seizure control
Antidotes: Sodium nitrite and sodium thiosulfate
Cyanide - Antidote
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Stage I – Sodium Nitrite:
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Methemoglobin-forming agent (high affinity for
cyanide)
Antidote should be infused slowly over 5-10
minutes
Nitrite induced hypotension
Pediatric dosing based on weight and hgb [ ]
Cyanide
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Stage I – Sodium Nitrite:
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Methemoglobin levels should be monitored
Levels peak at 35-70 minutes
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10-15% (therapeutic level)
Levels of 20-30%: headaches and nausea
Levels of 30-50%: weakness, dyspnea and
tachycardia
Levels of 50-70%: dysrhythmias, CNS depression and
seizures
Level of 70%: death
Cyanide
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Stage I – Sodium Nitrite:
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Amyl nitrite perles: administered first
Perles crushed in gauze and held near nose and
mouth for 30 seconds
Produces a methemoglobin level of 3-7 %
Once IV line established, sodium nitrite can be
administered
Little utility in severely toxic patient
Cyanide
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Stage II – Sodium thiosulfate:
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Provision of a sulfur donor
Conversion of cyanide → thiocyanate
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Less toxic
Renally excreted
Treatment:
Efficacious and benign
Used alone for mild to moderate cases
Cyanide
Taylor Cyanide Antidote Kit:
• Amyl Nitrite (inhaled) + Sodium nitrite (IV):
formation of methemoglobin which combines
with cyanide (high affinity)
• Sodium thiosulfate (IV) – produces
thiocyanate, excreted in urine
Cyanide
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New antidote under investigation:
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Hydroxocobalamin (vitamin B12a)
Cyanide couples with cobalt →
cyanocobalamin (nontoxic)
No hypotensive side effects (Na nitrite)
Pediatric data lacking
Summary/Take Home Points
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Decontamination
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Appropriate PPE
Disrobing, Water/soap
Peds considerations
Nerve Agents (Sarin)
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Acetylcholinesterase inhibitors → cholinergic
syndrome (SLUDGE) (3 B’s)
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NMJ: muscle fasciculation and twitching
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Respiratory/neurological symptoms
Antidote: Atropine/ 2-PAM
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Summary/Take Home Points
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Vessicants
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Derm/ocular manifestations
Severe: respiratory
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Sulfur mustard: garlic/mustard odor
Lewisite: geranium odor / antidote: BAL
Phosgene oxime: no vesicle formation
Pulmonary agents
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Severe respiratory symptoms/pulmonary edema
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Phosgene: newly mown hay smell
Summary/Take Home Points

Cyanide



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Lactate acidosis
Bitter almond smell
Seizures/coma
Antidote: Sodium nitrite and sodium thiosulfate
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Monitor methemoglobin levels
Other agents:
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Riot control agents
Incapacitating agents
Chemical Terrorism
THANKS!!