Chemical Terrorism

Amita Shroff, MD

June 10, 2010

Chemical Terrorism - Background

Dates back many years First use: World War I Modern use of chemical terrorism

Cyanide: Chicago, Illinois – 1984 Sarin :Tokyo, Japan-1995 Carbamate Insecticide: Fresno, California – 1999 Nicotine: Grand Rapids, Michigan – 2002

QUESTION 1

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? A. Dry Skin B. Miosis C. Normal Mental Status D. Constipation E. Hypotension

QUESTION 2

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 A. Supportive care only B. Atropine and 2-PAM C. Sodium Nitrite D. Midazolam E. Ciprofloxacin

QUESTION 3

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: A. Phosgene B. Sarin C. Cyanide D. Lewisite E.Mase

QUESTION 4

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: A. Soman B. Cyanide C. Sulfur Mustard D. Phosgene E. 1-Chloroacetophenone

QUESTION 5

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? 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

Apocalyptic groups Aum Shinrikyo, Japan (1995) Restoration of the 10 Commandments, Uganda

(2000) Political groups

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

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

Toxic effects: Topical injury

Skin Eyes Mucous membranes of respiratory tract

Systemic absorption Dermal Respiratory

Chemical Terrorism - Treatment

General treatment of contaminated victims: Triage Emergent resuscitation Decontamination if needed Airway / cardiopulmonary support Emergent antidotal therapy

Decontamination

Chemical Terrorism - Decontamination

Decontamination 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:

Warmer water (>37.8C) Low pressure systems

Chemical Terrorism - Decontamination

Vapor exposure: clothing removal and hair-washing (sufficient)

Liquid dermal exposure: thorough decontamination necessary

Ocular exposure: copious irrigation

Chemical Terrorism - PPE Level A

Highest level of protection Highly contaminated area (hot zone) Self contained breathing apparatus (SCBA) Fully encapsulated suit

Slightly pressurized Chemical resistant gloves

Hot, bulky and clumsy

Chemical Terrorism - PPE

Level B 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

Level C 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

Nerve agents Vesicants Pulmonary agents (irritant gases) Riot control agents Incapacitating agents Cyanide

Nerve Agents

Highly toxic Organophosphate insecticides (signs and

symptoms) Powerful inhibitors of acetylcholinesterase

(AChE) Acetylcholine accumulation → abnormal

neurotransmission

Nerve Agents

AchE inhibited by nerve agent →Acetylcholine accumulation → Abnl neurotransmission

Breakdown of Acetylcholine

Acetylcholine accumulation

Nerve Agents – Clinical Sx’s

Central Altered mental status → lethargy → coma, ataxia, convulsions and respiratory depression

Nicotinic

Neuromuscular junction

Sympathetic ganglion

Muscle fasciculation and twitching → weakness → flaccid paralysis

Tachycardia, hypertension and metabolic abnormalities (↑ glucose, ↓ K+, and acidosis)

Cholinergic Syndrome

Nerve Agents – Clinical Sx’s

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

Cholinergic Syndrome

Nerve Agents

Onset and type of symptoms depends: Concentration Route of exposure

Vital sign abnormalities: Sympathetic ganglia Parasympathetic ganglia

Nerve Agents - Exposure

Low doses: Miosis Cojunctival injection Pain Rhinorrhea

High doses: Respiratory effects

Severe exposure: Neurologic findings

Death: Respiratory depression and apnea

Nerve Agents - Exposure

Vapor exposure (triad): Ocular Nasal Respiratory

Dermal exposure (progression): Localized sweating and fasciculations → nausea,

vomiting , diarrhea and fatigue Severe exposure → respiratory and neurologic

symptoms

Nerve Agents

Children: 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

Self protection / PPE (contamination HIGH) Agents readily absorbed Patient decontamination:

Warm water / soap ? Diluted bleach solution (adults)

Nerve Agents - Management

Restoring ventilation and oxygenation Aggressive use of antidotes Cardiac monitoring: dysrhythmias (torsades) Benzodiazepines – neuroprotective Close observation

Nerve Agents - Antidote

Atropine .05 -.10 mg/kg IV or IM Min 0.1mg, max 5mg Repeat Q 2-5 min for secretions Pralidoxime (2-PAM) 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 attack on agent)

• Reverses nicotinic, muscarinic and CNS effects

• Weakness

• Fasciculations

Nerve Agents - Antidote

Military Mark I autoinjector kits: 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

Aging: permanent inhibition of AChE activity (irreversible covalent binding)

Need early 2-PAM therapy prior to aging

Nerve Agents

Difference from organophosphate pesticide poisoning: Continuous infusions usually not necessary

(atropine or 2-PAM) Delayed peripheral neuropathies not seen

Life support + antidotal therapy →prognosis good

Potential advances in treatment: More effective oximes: HI-6 Fetal bovine serum acetylcholinesterase

Vesicants

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)

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

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)

Symptoms: 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)

Systemic absorption involves: Hematopoietic GI CNS

Expected mortality = 3% for those reaching medical facility

Children: More rapid onset Worse dermal reactions

Vesicants - Sulfur Mustard (SM)

Vesicants – Lewisite (L)

Vesicants – Lewisite (L)

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)

Skin lesions: 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)

BAL (British anti-Lewisite) or dimercaprol: 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)

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)

Ocular findings similar to lewisite Pulmonary edema is common and may see

bronchiolitis

Vesicants 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

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

No antidote Aggressive airway, fluid, electrolyte and pain

management ? GCSF - mustard induced leukopenia Infection prevention with antibiotics Burn center referral

Pulmonary Agents (Irritant Gases)

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, D-Stoff, or green cross)

Chlorine

Nitrogen oxides

Ammonia

Pulmonary Agent - Phosgene

Pulmonary Agents - Phosgene

Gas with a density 4X that of air Found in plastics, pharmaceutical and textile

industries When released:

forms a white cloud odor of newly mown hay

Water insoluble

Pulmonary Agents - Phosgene

Initially asymptomatic with perception of odor Mild exposure:

Eyes, nose, throat and upper airway irritation Major toxicity:

Acid burn to lower airways Diffuse capillary leak Pulmonary edema

Pulmonary edema: delay 4-6 hrs (as late as 24 hrs)

Pulmonary Agents – Phosgene

Management Primarily supportive care Decontamination: removal of victim to fresh air Respiratory:

Pulmonary secretions Bronchospasm Pulmonary edema

Aggressive treatment of secondary bacterial infections

Pulmonary Agents - Phosgene

Management: Steroids: ?severe bronchospasm Anti-inflammatory agents (NAC/ibuprofen): ?

pulmonary edema 24- hour observation for all asymptomatic patients

Pulmonary Agents - Phosgene

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 Widely available Dense, green-yellow gas with pungent odor Intermediate water solubility → upper + lower

airways affected Early inflammatory injury

Formation of acids and oxidants upon contact with moist mucous membranes

Pulmonary Agents - Chlorine

Mild Exposure: Immediate ocular, nasal and upper airway

irritation Nausea and vomiting

Severe Exposure: (sx within 12-24 hrs) Coughing and hoarseness Pulmonary edema Permanent reactive airway disease (inhalation)

Pulmonary Agents - Chlorine

Management: Supportive care Humidified oxygen Bronchodilators ? Nebulized sodium bicarbonate (3.75%) solution Skin decontamination

Pulmonary Agents-Nitrogen Oxide

Silo gas: Product of fire combustion Industrial process Military blast weapons

Limited water solubility Lower airway toxicity

Nitrogen oxide converted to nitric acid → alveolar injury → pulmonary edema

Pulmonary Agents-Nitrogen Oxide

Triphasic illness: Dyspnea and flu-like symptoms Transient improvement Pulmonary edema with worsening dyspnea (24-

72 hrs) Other consequences:

Methemoglobinemia Bronchiolitis obliterans (late complication)

Pulmonary Agents - Ammonia

Fertilizer and industrial chemical Highly water soluble Colorless, alkaline, corrosive gas Rapidly reacts with water to form ammonium

hydroxide Pungent odor

Pulmonary Agents - Ammonia

Immediate eye, mucous membrane and throat irritation

Lower airway involvement: Bronchospasm Pulmonary edema Reactive airway disease

Pulmonary Agents - Ammonia

Treatment Supportive Humidified oxygen and bronchodilators Ocular irrigation → evaluation for corneal burns

Riot Control Agents

Riot Control Agents

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 Symptoms

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

Management Removal from exposure Copious ocular irrigation Skin decontamination

Incapacitating Agents - Military

Military incapacitating agents: physiologic or mental effects

Usually not lethal Recovery: several hours to days Anticholinergic deliriants (QNB, BZ)

Incapacitating Agents Signs and symptoms (Anticholinergic):

Delirium Hallucinations Mydriasis Tachycardia Ileus Dry mucous membranes Absent axillary sweat Urinary retention Hyperthermia

Incapacitating Agents

Treatment: Supportive care Benzodiazepines to prevent:

Hyperthermia Rhabdomyolysis

Physostigmine: Refractory seizures Profound tachycardia

Incapacitating Agents Other incapacitation agents: (besides military

agents) Stimulants Potent opioids (carfentanyl, aerosol fentanyl) Hallucinogens (LSD, Cannabinoids) Vomiting Agents

Cyanide

Long term use as a toxin for sinister purposes Chemical terrorism agent: limited

volatility in open air low lethality compared to nerve gas

Devastating effects in a crowded, closed room

Cyanide

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

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

Mild exposures: Tachypnea and hyperpnea Tachycardia Flushing Dizziness and headaches Diaphoresis Nausea and vomiting

Serious exposures: Seizures, coma and apnea Cardiac arrest

Cyanide

Cyanide

Laboratory findings: 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

Management: Removal of victim to fresh air Removal of any wet clothing and skin decon Intensive supportive care

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

Cyanide - Antidote Stage I – Sodium Nitrite:

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

Stage I – Sodium Nitrite: Methemoglobin levels should be monitored Levels peak at 35-70 minutes

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

Stage I – Sodium Nitrite: 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

Stage II – Sodium thiosulfate: Provision of a sulfur donor Conversion of cyanide → thiocyanate

Less toxic Renally excreted

Treatment: Efficacious and benign Used alone for mild to moderate cases

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

Cyanide

New antidote under investigation: Hydroxocobalamin (vitamin B12a)

Cyanide couples with cobalt → cyanocobalamin (nontoxic)

No hypotensive side effects (Na nitrite) Pediatric data lacking

Summary/Take Home Points

Decontamination Appropriate PPE Disrobing, Water/soap Peds considerations

Nerve Agents (Sarin) Acetylcholinesterase inhibitors → cholinergic

syndrome (SLUDGE) (3 B’s) NMJ: muscle fasciculation and twitching Respiratory/neurological symptoms Antidote: Atropine/ 2-PAM

Summary/Take Home Points

Vessicants Derm/ocular manifestations Severe: respiratory

Sulfur mustard: garlic/mustard odor Lewisite: geranium odor / antidote: BAL Phosgene oxime: no vesicle formation

Pulmonary agents Severe respiratory symptoms/pulmonary edema

Phosgene: newly mown hay smell

Summary/Take Home Points

Cyanide Lactate acidosis Bitter almond smell Seizures/coma Antidote: Sodium nitrite and sodium thiosulfate

Monitor methemoglobin levels

Other agents: Riot control agents Incapacitating agents

Chemical Terrorism

THANKS!!