BRIEFING VESICANTS.pdf

7/29/2019 BRIEFING VESICANTS.pdf

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USAMRICDPROTECT, PROJECT, SUSTAI N

MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES

U.S. ARMY MEDICAL RESEARCH

INSTITUTE OF CHEMICAL DEFENSE

VESICANTS


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VESICANTS

USAMRICDPROJECT, PROTECT, SUSTAI N

VESICANTS 2

OBJECTIVES Know the mechanism of action (pathophysiology)

Identify signs and symptoms for all routes ofexposure and the clinical time course

Know specific pre and post exposure treatmentregimens

Understand the specific pharmacology of each

treatment regimen Understand the prognosis and triage for mild,

moderate, and severe exposure


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VESICANTS


VESICANTS 4

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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VESICANTS 5

WORLD WAR I CW CASUALTIESCW Casualties %Fatal

Germany 200,000 4.5

France 190,000 4.2

Britain 189,000 4.2

U.S. 73,000 2.0Russia 475,000 11.8

Kurds 5,000 100?


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VESICANTS 6

WW I USE Caused more than 70% of chemical casualties

Lethality low; under 5%

Long convalescence


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VESICANTS 7

WORLD WAR II The Bari mustard disaster

02 December 1943


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VESICANTS 8

POST-WORLD WAR I

Italy against Ethiopia

Japan against China

Iraq against Iran, Kurds

Alleged: Egypt against Yemen


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VESICANTS 9

MUSTARD

HS: Hun Stoff

H: Impure

HD: Distilled, pure

HL: Mustard/Lewisite

HT: Mustard/agent T


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SULFUR MUSTARDCH2 - CH2 - Cl

Mustard S

CH2 - CH2 - Cl

CH2 - CH2 - OH

Thiodiglycol S

CH2 - CH2 - OH


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VESICANTS


VESICANTS 11

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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VESICANTS 12

MUSTARD DETECTION

Liquid: M8, M9 papers

Vapor: M256A1; CAM


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VESICANTS 13

MUSTARD PENETRATION

Through skin surfaces in 2 minutes

80% on skin evaporates

Part is fixed in skin, rest circulates


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VESICANTS 14

MUSTARD

Quickly cyclizes in tissue

Alkylates cell components(DNA, proteins)

DNA damage leads to:cell deathmutation


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MUSTARD TOXICITY

Vapor unprotected (mgmin/m3)

Eye 10 to 50

Airways 100 to 500

Skin 200 to 1,000Death 1,500


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VESICANTS 16

Liquid

Blister 10ug

Death 100 mg/kg

7 gm/70 kg

MUSTARD TOXICITY

CONTINUEDCONTINUED


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VESICANTS 17

MUSTARD: DAMAGES

Skin

Eyes

Airways

Systemic:

Bone marrow

GI tract CNS

Lymphoid tissue


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VESICANTS 18

MUSTARD CASUALTIES FROM WWI

Eyes...85%

Respiratory Tract...75%

Scrotum .....42%

Face ...27%

Anus .24%

Legs....11%

Buttocks .....10% Hands .....4%

Feet...1.5%


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VESICANTS 19

MUSTARD: ONSET

Cellular interaction: 1 to 2 minutes

Clinical effects: 2 to 48 hours

Usually 4 to 8 hours


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VESICANTS 20

MUSTARD: SKIN

Erythema

Small vesicles; later coalesce

Blisters/bulla

Possible coagulation necrosis with liquidexposure


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VESICANTS 21

MUSTARD: ONSET

Chemical cell damage: 1 to 2 minutes

Clinical effects: 2 to 48 hours

Usually 4 to 8 hours


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VESICANTS 22

MUSTARD: EYE

Mild: conjunctivitis, blepharospasm

Moderate: lid inflammation and edema,blepharospasm, corneal roughening

Severe: Corneal opacification, ulceration,and/or perforation


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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

CONTINUEDCONTINUED


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VESICANTS


VESICANTS 24

MUSTARD: ACUTE EFFECTS

Upper airway

Hemorrhage

Pain

Larynx

Hoarseness

Stridor


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VESICANTS 25

MUSTARD: ACUTE EFFECTS

Trachea/bronchi

bronchospasm

pseudomembranes

Small airway and alveoli

(massive exposure)hemorrhagic edema

CONTINUEDCONTINUED


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MUSTARD: DEATH

Usually pulmonary:

Damaged airways

Infection

Depressed immune system

Sepsis


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VESICANTS 27

MUSTARD: MARROW

Damaged stem cells

Decreased WBC, RBC, platelets(Day 7 to day 14)

Survival rare if WBC


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MUSTARD: GI

Early (< 24 hours):

transient symptoms

cholinergic effect

Late (>3 days):

severe damage

cytotoxic effect


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SEVERE MUSTARD EXPOSURE

CNS

Apathy, lethargy

Euphoria

Convulsions, only with massive exposure!

Coma

Death


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VESICANTS 30

MUSTARD

Radiomimetic (DNA)

epithelial cells(eye, pulmonary, skin, GI)

hematopoetic

damages many tissues


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MUSTARD: SYMPTOMS

Symptoms within 4 hours = severe injury

Airway symptoms within 6 hours is often

fatal


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DIFFERENTIAL DIAGNOSIS

Isolated cases: plant, animal, other chemicals

Many cases:

Latent effects: Mustard

Immediate effects: Lewisite, Phosgene Oxime


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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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MUSTARD: MANAGEMENT

Protect Self!!!


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DECONTAMINATION

Early decon protects casualty

within minutes

Late decon protects medical personnel and

facility


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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


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MANAGEMENT: EYES

Soothing eye drops

Topical mydriatics

Topical antibiotics

Vaseline on lid edges

Avoid topical analgesics

Topical steroids - ??

Sunglasses


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MANAGEMENT: AIRWAYS

Steam, cough suppressants

Oxygen

Bronchodilators, steroids

Early intubation

Assisted ventilation

Antibiotics AFTER organism identified


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MANAGEMENT: GI

Atropine

Antiemetics

Fluid therapy

Electrolyte replacement


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MANAGEMENT: MARROW

Blood component replacement

RBC, WBC, Platelets

Marrow transplants

Hormonal therapy

Reverse isolation


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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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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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LEWISITE

Oily, amber to brown liquid

Freezing point ~ 0F

Heavier than air, water

Persistent

Geranium odor

CONTINUEDCONTINUED


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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 14 g

Death 2.8 g


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LEWISITE: MECHANISM

Contains arseniccarcinogen ??

Reacts with many constituents: cellularnecrosis

Mechanism unknown


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LEWISITE: DAMAGES

Eyes

Skin

Airways

Capillaries


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LEWISITE: TIME OF ONSET

Pain, irritation within 1 min

Tissue necrosis within 5 min


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LEWISITE: SKIN

Progresses to blister

More necrosis than from mustard


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LEWISITE: EYES

Pain, blepharospasm on contact

Rapid edema of conjunctiva, lidsEyes swollen shut in an hour

Damage to iris and cornea


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LEWISITE: AIRWAYS

Severe irritation

Bronchial epithelial necrosis, similar tomustard

More prone to pseudomembranes, pulmonary

edema than mustard


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VESICANTS 52

LEWISITE SHOCK

Increased capillary permeability

Plasma volume decreased

Hemoconcentration

Hypotension

Pulmonary edema

Circulatory failure

Death


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VESICANTS 53

LEWISITE: MANAGEMENT

Immediate decontamination

Treat as mustard lesion

British Anti-lewisite (BAL)

Dimercaprol

Systemic

Topical

Ophthalmic


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VESICANTS 54

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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BAL SIDE EFFECTS

Lacrimation

Constriction of throat

GI cramps, vomiting, nausea

Anxiety, myalgias

Hypertension May last up to 30 minutes

VESICANTS


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PHOSGENE OXIME (CX)

Rapid onset

Toxic, irritating, corrosive

Urticant, not vesicant

Sparse data

Never used in combat

Stockpiled by USSR

VESICANTS


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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

VESICANTS


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PHOSGENE OXIME: MANAGEMENT

Management:

Symptomatic

Supportive

Same as mustard


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USAMRICDPROTECT, PROJECT, SUSTAI N

MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES

U.S. ARMY MEDICAL RESEARCH

INSTITUTE OF CHEMICAL DEFENSE

SUMMARY

ANY QUESTIONS?

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BRIEFING VESICANTS.pdf