Dates back many years

Dates back many years

• 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

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?

• 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

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

• 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

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:

• 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

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 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

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?

• 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

Apocalyptic groups

• 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)

Aum Shinrikyo converge at Kasumigaseki subway station

• 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.

Toxic effects:

• Toxic effects:

• Topical injury
• Skin
• Eyes
• Mucous membranes of respiratory tract
• Systemic absorption
• Dermal
• Respiratory

General treatment of contaminated victims:

• General treatment of contaminated victims:

• Triage
• Emergent resuscitation
• Decontamination if needed
• Airway / cardiopulmonary support
• Emergent antidotal therapy

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

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

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

• Liquid dermal exposure: thorough decontamination necessary

• Ocular exposure: copious irrigation

Level A

• 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

Level B

• 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

Level C

• 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

Nerve agents

• Nerve agents

• Vesicants

• Pulmonary agents (irritant gases)

• Riot control agents

• Incapacitating agents

• Cyanide

Highly toxic

• Highly toxic

• Organophosphate insecticides (signs and symptoms)

• Powerful inhibitors of acetylcholinesterase (AChE)

• Acetylcholine accumulation → abnormal neurotransmission

Onset and type of symptoms depends:

• Onset and type of symptoms depends:

• Concentration
• Route of exposure

• Vital sign abnormalities:

• Sympathetic ganglia
• Parasympathetic ganglia

Low doses:

• Low doses:

• Miosis
• Cojunctival injection
• Pain
• Rhinorrhea

• High doses:

• Respiratory effects

• Severe exposure:

• Neurologic findings

• Death:

• Respiratory depression and apnea

Vapor exposure (triad):

• Vapor exposure (triad):

• Ocular
• Nasal
• Respiratory

• Dermal exposure (progression):

• Localized sweating and fasciculations → nausea, vomiting , diarrhea and fatigue
• Severe exposure → respiratory and neurologic symptoms

Children:

• 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

Self protection / PPE (contamination HIGH)

• Self protection / PPE (contamination HIGH)

• Agents readily absorbed

• Patient decontamination:

• Warm water / soap
• ? Diluted bleach solution (adults)

Restoring ventilation and oxygenation

• Restoring ventilation and oxygenation

• Aggressive use of antidotes

• Cardiac monitoring: dysrhythmias (torsades)

• Benzodiazepines – neuroprotective

• Close observation

• 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)

Military Mark I autoinjector kits:

• 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

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

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

• Need early 2-PAM therapy prior to aging

Difference from organophosphate pesticide poisoning:

• 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: agents that produce blistering

• Vesicants: agents that produce blistering

• Severe dermal manifestation in children

• Released as an aerosol

• 3 primary vesicants:

Most viable threat ( ≥ 12 countries have SM in their arsenals)

• 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

• 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

Symptoms:

• 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

Systemic absorption involves:

• Systemic absorption involves:

• Hematopoietic
• GI
• CNS

• Expected mortality = 3% for those reaching medical facility

• Children:

• More rapid onset
• Worse dermal reactions

Potency similar to sulfur mustard

• 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

Skin lesions:

• 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

BAL (British anti-Lewisite) or dimercaprol:

• 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

Extensive tissue damage

• 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

Ocular findings similar to lewisite

• Ocular findings similar to lewisite

• Pulmonary edema is common and may see bronchiolitis

Vesicant toxicity: clinical diagnosis

• 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

PPE for healthcare workers

• 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

No antidote

• No antidote

• Aggressive airway, fluid, electrolyte and pain management

• ? GCSF - mustard induced leukopenia

• Infection prevention with antibiotics

• Burn center referral

Pulmonary agents classified according to anatomical infliction

• Pulmonary agents classified according to anatomical infliction

• Affect central or peripheral pulmonary system

• Central: Upper airways (cough or stridor)

• Peripheral: lower airways (pulmonary edema)

Gas with a density 4X that of air

• 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

Initially asymptomatic with perception of odor

• 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)

Management

• Management

• Primarily supportive care
• Decontamination: removal of victim to fresh air
• Respiratory:
• Pulmonary secretions
• Bronchospasm
• Pulmonary edema
• Aggressive treatment of secondary bacterial infections

Management:

• Management:

• Steroids: ?severe bronchospasm
• Anti-inflammatory agents (NAC/ibuprofen): ? pulmonary edema
• 24- hour observation for all asymptomatic patients

Poor prognosis: dyspnea or pulmonary edema within 4 hours

• 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

Widely available

• 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

Mild Exposure:

• 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)

Management:

• Management:

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

Silo gas:

• 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

Triphasic illness:

• Triphasic illness:

• Dyspnea and flu-like symptoms
• Transient improvement
• Pulmonary edema with worsening dyspnea (24-72 hrs)

• Other consequences:

• Methemoglobinemia
• Bronchiolitis obliterans (late complication)

Fertilizer and industrial chemical

• Fertilizer and industrial chemical

• Highly water soluble

• Colorless, alkaline, corrosive gas

• Rapidly reacts with water to form ammonium hydroxide

• Pungent odor

Immediate eye, mucous membrane and throat irritation

• Immediate eye, mucous membrane and throat irritation

• Lower airway involvement:

• Bronchospasm
• Pulmonary edema
• Reactive airway disease

Treatment

• Treatment

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

Lacrimators or “tear gas”

• 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

Symptoms

• 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

Management

• Management

• Removal from exposure
• Copious ocular irrigation
• Skin decontamination

Military incapacitating agents: physiologic or mental effects

• Military incapacitating agents: physiologic or mental effects

• Usually not lethal

• Recovery: several hours to days

• Anticholinergic deliriants (QNB, BZ)

Signs and symptoms (Anticholinergic):

• Signs and symptoms (Anticholinergic):

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

Treatment:

• Treatment:

• Supportive care
• Benzodiazepines to prevent:
• Hyperthermia
• Rhabdomyolysis
• Physostigmine:
• Refractory seizures
• Profound tachycardia

Other incapacitation agents: (besides military agents)

• Other incapacitation agents: (besides military agents)

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

Long term use as a toxin for sinister purposes

• 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

Toxicity: Interference with normal mitochondrial oxidation → lactic acidosis

• Toxicity: Interference with normal mitochondrial oxidation → lactic acidosis

• High affinity for ferric iron (Fe3+)

• Brain and heart targeted because most dependent on oxidative phosphorylation

Clinical presentation: route and dose of exposure

• 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:

• Mild exposures:

• Tachypnea and hyperpnea
• Tachycardia
• Flushing
• Dizziness and headaches
• Diaphoresis
• Nausea and vomiting

• Serious exposures:

• Seizures, coma and apnea
• Cardiac arrest

Laboratory findings:

• 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:

• 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

Stage I – Sodium Nitrite:

• 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 [ ]

Stage I – Sodium Nitrite:

• 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

Stage I – Sodium Nitrite:

• 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

Stage II – Sodium thiosulfate:

• 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:

• 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

New antidote under investigation:

• New antidote under investigation:

• Hydroxocobalamin (vitamin B12a)

• Cyanide couples with cobalt → cyanocobalamin (nontoxic)

• No hypotensive side effects (Na nitrite)

• Pediatric data lacking

Decontamination

• 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

Vessicants

• 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

Cyanide

• Cyanide

• Lactate acidosis
• Bitter almond smell
• Seizures/coma
• Antidote: Sodium nitrite and sodium thiosulfate
• Monitor methemoglobin levels

• Other agents:

• Riot control agents
• Incapacitating agents