MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES

VESICANTS
U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE USAMRICD
PROTECT, PROJECT, SUSTAIN

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OBJECTIVES
Know the mechanism of action (pathophysiology) Identify signs and symptoms for all routes of exposure and the clinical time course Know specific pre and post exposure treatment regimens Understand the specific pharmacology of each treatment regimen Understand the prognosis and triage for mild, moderate, and severe exposure
VESICANTS 2

USAMRICD
PROJECT, PROTECT, SUSTAIN

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MILITARY VESICANTS Mustards

Sulfur (agent) Nitrogen (chemotherapy)

Lewisite Phosgene oxime

VESICANTS 3

USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD HISTORY
1822: First synthesized (Despretz) Mid-1800s: Synthesized again (Niemann, Guthrie) 1880s: Manufacturing process (Meyer) 1917: First battlefield use (Germany)
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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WORLD WAR I CW CASUALTIES

Germany France Britain U.S. Russia Kurds
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CW Casualties 200,000 190,000 189,000 73,000 475,000 5,000

%Fatal 4.5 4.2 4.2 2.0 11.8 100?

USAMRICD
PROJECT, PROTECT, SUSTAIN

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WW I USE
Caused more than 70% of chemical casualties Lethality low; under 5% Long convalescence

VESICANTS 6

USAMRICD
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WORLD WAR II
The Bari mustard disaster 02 December 1943

VESICANTS 7

USAMRICD
PROJECT, PROTECT, SUSTAIN

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POST-WORLD WAR I
Italy against Ethiopia Japan against China Iraq against Iran, Kurds Alleged: Egypt against Yemen
VESICANTS 8

USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD
HS: Hun Stoff H: Impure HD: Distilled, pure HL: Mustard/Lewisite HT: Mustard/agent T
VESICANTS 9

USAMRICD
PROJECT, PROTECT, SUSTAIN

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SULFUR MUSTARD
CH2 - CH2 - Cl Mustard S CH2 - CH2 - Cl CH2 - CH2 - OH Thiodiglycol S CH2 - CH2 - OH
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD
Oily liquid Light yellow to brown Vapor heavier than air Liquid heavier than water Low volatility; persistent Freezes/melts at 58F
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD DETECTION
Liquid: M8, M9 papers Vapor: M256A1; CAM

VESICANTS 12

USAMRICD
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MUSTARD PENETRATION Through skin surfaces in 2 minutes 80% on skin evaporates Part is fixed in skin, rest circulates
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD
Quickly cyclizes in tissue Alkylates cell components (DNA, proteins) DNA damage leads to:
cell death mutation
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD TOXICITY
Vapor unprotected (mgmin/m3) Eye Airways Skin Death
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10 to 50 100 to 500 200 to 1,000 1,500

USAMRICD
PROJECT, PROTECT, SUSTAIN

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CONTINUED

MUSTARD TOXICITY
Liquid Blister Death 10ug 100 mg/kg 7 gm/70 kg

VESICANTS 16

USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: DAMAGES
Skin Eyes Airways Systemic:
Bone marrow GI tract CNS Lymphoid tissue
USAMRICD
PROJECT, PROTECT, SUSTAIN

VESICANTS 17

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MUSTARD CASUALTIES FROM WWI

Eyes...85% Respiratory Tract...75% Scrotum .....42% Face ...27% Anus .24% Legs....11% Buttocks .....10% Hands .....4% Feet...1.5%
USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: ONSET Cellular interaction: 1 to 2 minutes Clinical effects: 2 to 48 hours Usually 4 to 8 hours
USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: SKIN
Erythema Small vesicles; later coalesce Blisters/bulla Possible coagulation necrosis with liquid exposure
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: ONSET
Chemical cell damage: 1 to 2 minutes Clinical effects: Usually 4 to 8 hours 2 to 48 hours

VESICANTS 21

USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: EYE
Mild: conjunctivitis, blepharospasm Moderate: lid inflammation and edema, blepharospasm, corneal roughening Severe: Corneal opacification, ulceration, and/or perforation
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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CONTINUED

MUSTARD: EYE
75% only mild conjunctivitis
Return to duty in 2 weeks

15% moderate conjunctivitis

Return to duty 4-6 weeks

10% severe; under 1% with residual damage 0.1% legal blindness

VESICANTS 23

USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: ACUTE EFFECTS

Upper airway
Hemorrhage Pain

Larynx
Hoarseness Stridor
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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CONTINUED

MUSTARD: ACUTE EFFECTS

Trachea/bronchi
bronchospasm pseudomembranes

Small airway and alveoli (massive exposure)

hemorrhagic edema
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: DEATH Usually pulmonary:

Damaged airways Infection Depressed immune system Sepsis
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: MARROW
Damaged stem cells Decreased WBC, RBC, platelets (Day 7 to day 14) Survival rare if WBC <200 (Iran / Iraq)
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: GI
Early (< 24 hours):
transient symptoms cholinergic effect

Late (>3 days):

severe damage cytotoxic effect
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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SEVERE MUSTARD EXPOSURE

CNS
Apathy, lethargy Euphoria Convulsions, only with massive exposure! Coma Death
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD
Radiomimetic (DNA)
epithelial cells (eye, pulmonary, skin, GI) hematopoetic damages many tissues
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: SYMPTOMS
Symptoms within 4 hours = severe injury Airway symptoms within 6 hours is often fatal

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USAMRICD
PROJECT, PROTECT, SUSTAIN

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DIFFERENTIAL DIAGNOSIS
Isolated cases: plant, animal, other chemicals Many cases:
Latent effects: Mustard Immediate effects: Lewisite, Phosgene Oxime
USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: DIAGNOSTICS
Non-specific CBC Early chemical pneumonitis: fever, WBC, chest x-ray Pneumonia: sputum exam / culture Urinary thiodiglycol: DA TB Med 296
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: MANAGEMENT

Protect Self!!!

VESICANTS 34

USAMRICD
PROJECT, PROTECT, SUSTAIN

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DECONTAMINATION
Early decon protects casualty within minutes Late decon protects medical personnel and facility

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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MANAGEMENT: SKIN
Soothing cream/lotion Unroof large blisters Debridement of burns Frequent irrigation Antibiotics: Topical / Systemic (cellulitis) Systemic analgesics Appropriate IV fluids and electrolytes
USAMRICD
PROJECT, PROTECT, SUSTAIN

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MANAGEMENT: EYES
Soothing eye drops Topical mydriatics Topical antibiotics Vaseline on lid edges Avoid topical analgesics Topical steroids - ?? Sunglasses
USAMRICD
PROJECT, PROTECT, SUSTAIN

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MANAGEMENT: AIRWAYS
Steam, cough suppressants Oxygen Bronchodilators, steroids Early intubation Assisted ventilation Antibiotics AFTER organism identified
USAMRICD
PROJECT, PROTECT, SUSTAIN

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MANAGEMENT: GI
Atropine Antiemetics Fluid therapy Electrolyte replacement
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MANAGEMENT: MARROW
Blood component replacement
RBC, WBC, Platelets

Marrow transplants Hormonal therapy Reverse isolation

VESICANTS 40

USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: LONG TERM

Carcinogen / mutagen No evidence of human reproductive toxicity Chronic exposure
Respiratory cancer Unclear: chronic bronchitis, emphysema
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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MUSTARD: LONG TERM

No evidence of cancer after one or two exposures Chronic eye problems / damage may follow severe eye exposure

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LEWISITE
World War I origin; not used Possible use by Japan vs China No other known use Sparse data
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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CONTINUED

LEWISITE
Oily, amber to brown liquid Freezing point ~ 0F Heavier than air, water Persistent Geranium odor
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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LEWISITE: TOXICITY
Vapor
Eyes Effects 2 mg-min/m3 Vesication 1,500 mg-min/m3 Death 1,500 mg-min/m3

Liquid
Blister Death
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14 g 2.8 g
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PROJECT, PROTECT, SUSTAIN

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LEWISITE: MECHANISM
Contains arsenic
carcinogen ??

Reacts with many constituents: cellular necrosis Mechanism unknown

VESICANTS 46

USAMRICD
PROJECT, PROTECT, SUSTAIN

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LEWISITE: DAMAGES
Eyes Skin Airways Capillaries
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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LEWISITE: TIME OF ONSET Pain, irritation within 1 min Tissue necrosis within 5 min

VESICANTS 48

USAMRICD
PROJECT, PROTECT, SUSTAIN

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LEWISITE: SKIN
Progresses to blister More necrosis than from mustard

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USAMRICD
PROJECT, PROTECT, SUSTAIN

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LEWISITE: EYES
Pain, blepharospasm on contact Rapid edema of conjunctiva, lids
Eyes swollen shut in an hour

Damage to iris and cornea

VESICANTS 50

USAMRICD
PROJECT, PROTECT, SUSTAIN

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LEWISITE: AIRWAYS
Severe irritation Bronchial epithelial necrosis, similar to mustard More prone to pseudomembranes, pulmonary edema than mustard

VESICANTS 51

USAMRICD
PROJECT, PROTECT, SUSTAIN

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LEWISITE SHOCK
Increased capillary permeability
Plasma volume decreased Hemoconcentration Hypotension Pulmonary edema Circulatory failure Death
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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LEWISITE: MANAGEMENT
Immediate decontamination Treat as mustard lesion British Anti-lewisite (BAL) Dimercaprol
Systemic Topical Ophthalmic
VESICANTS 53

USAMRICD
PROJECT, PROTECT, SUSTAIN

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LEWISITE: TREATMENT
Hospital care - severe exposure
IM injection of BAL (10% in oil) Initial dose: 0.5cc per 25 lbs (up to 4cc total) May be given at 4, 8, 12 hours after initial dose
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USAMRICD
PROJECT, PROTECT, SUSTAIN

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BAL SIDE EFFECTS

Lacrimation Constriction of throat GI cramps, vomiting, nausea Anxiety, myalgias Hypertension May last up to 30 minutes
VESICANTS 55

USAMRICD
PROJECT, PROTECT, SUSTAIN

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PHOSGENE OXIME (CX)

Rapid onset Toxic, irritating, corrosive Urticant, not vesicant Sparse data Never used in combat Stockpiled by USSR
USAMRICD
PROJECT, PROTECT, SUSTAIN

VESICANTS 56

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PHOSGENE OXIME (CX)

Phosgene oxime corrosive to all tissues (skin, lungs, eyes)
Pulmonary edema

Phosgene oxime manufactured from Phosgene Phosgene (CG) - lung agent only
USAMRICD
PROJECT, PROTECT, SUSTAIN

VESICANTS 57

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PHOSGENE OXIME: MANAGEMENT Management:

Symptomatic Supportive Same as mustard
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USAMRICD
PROJECT, PROTECT, SUSTAIN

MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES

SUMMARY ANY QUESTIONS?

U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE USAMRICD
PROTECT, PROJECT, SUSTAIN