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MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES

VESICANTS

U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE

MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES VESICANTS U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE USAMRICD PROTECT,

USAMRICD

PROTECT, PROJECT, SUSTAIN

MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES VESICANTS U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE USAMRICD PROTECT,

VESICANTS

VESICANTS OBJECTIVES • Know the mechanism of action (pathophysiology) • Identify signs and symptoms for all

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

VESICANTS

VESICANTS MILITARY VESICANTS • Mustards – Sulfur (agent) – Nitrogen (chemotherapy) • Lewisite • Phosgene oxime

MILITARY VESICANTS Mustards

Sulfur (agent) Nitrogen (chemotherapy)

Lewisite Phosgene oxime

VESICANTS 3

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD HISTORY • 1822: First synthesized (Despretz) • Mid-1800s: Synthesized again (Niemann, Guthrie) • 1880s:

MUSTARD HISTORY

1822: First synthesized (Despretz)

Mid-1800s: Synthesized again (Niemann, Guthrie)

1880s: Manufacturing process (Meyer)

1917: First battlefield use (Germany)

VESICANTS 4

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS WORLD WAR I CW CASUALTIES CW Casualties %Fatal Germany 200,000 4.5 France 190,000 4.2 Britain

WORLD WAR I CW CASUALTIES

CW Casualties

%Fatal

Germany

200,000

4.5

France

190,000

4.2

Britain

189,000

4.2

U.S.

73,000

2.0

Russia

475,000

11.8

Kurds

5,000

100?

VESICANTS 5

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS WW I USE • Caused more than 70% of chemical casualties • Lethality low; under

WW I USE

Caused more than 70% of chemical casualties

Lethality low; under 5%

Long convalescence

VESICANTS 6

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS WORLD WAR II • The Bari mustard disaster • 02 December 1943 VESICANTS 7 USAMRICD

WORLD WAR II

The Bari mustard disaster 02 December 1943

VESICANTS 7

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS POST-WORLD WAR I • Italy against Ethiopia • Japan against China • Iraq against Iran,

POST-WORLD WAR I

Italy against Ethiopia

Japan against China

Iraq against Iran, Kurds

Alleged: Egypt against Yemen

VESICANTS 8

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD • HS: Hun Stoff • H: Impure • HD: Distilled, pure • HL: Mustard/Lewisite

MUSTARD

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

VESICANTS 9

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS SULFUR MUSTARD Mustard Thiodiglycol VESICANTS 10 S CH - CH - Cl CH - CH

SULFUR MUSTARD

Mustard

Thiodiglycol

VESICANTS 10

S

CH 2 - CH 2 - Cl

  • CH 2 - CH 2 - Cl

S

CH 2 - CH 2 - OH

  • CH 2 - CH 2 - OH

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD • Oily liquid • Light yellow to brown • Vapor heavier than air •

MUSTARD

Oily liquid Light yellow to brown Vapor heavier than air Liquid heavier than water Low volatility; persistent Freezes/melts at 58°F

VESICANTS 11

VESICANTS MUSTARD • Oily liquid • Light yellow to brown • Vapor heavier than air •

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD DETECTION • Liquid: M8, M9 papers • Vapor: M256A1; CAM VESICANTS 12 USAMRICD PROJECT,

MUSTARD DETECTION

Liquid: M8, M9 papers

Vapor: M256A1; CAM

VESICANTS 12

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD PENETRATION • Through skin surfaces in 2 minutes • 80% on skin evaporates •

MUSTARD PENETRATION

Through skin surfaces in 2 minutes 80% on skin evaporates Part is “fixed” in skin, rest circulates

VESICANTS 13

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD • Quickly cyclizes in tissue • Alkylates cell components (DNA, proteins) • DNA damage

MUSTARD

Quickly cyclizes in tissue

Alkylates cell components (DNA, proteins)

DNA damage leads to:

cell death mutation

VESICANTS 14

VESICANTS MUSTARD • Quickly cyclizes in tissue • Alkylates cell components (DNA, proteins) • DNA damage

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD TOXICITY Vapor unprotected (mg•min/m ) Eye 10 to 50 Airways 100 to 500 Skin

MUSTARD TOXICITY

Vapor unprotected (mg•min/m 3 )

Eye

10 to 50

Airways

100 to 500

Skin

200 to 1,000

Death

1,500

VESICANTS 15

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

 

CONTINUED

CONTINUED

 

MUSTARD TOXICITY

Blister

Death

Liquid

10ug

100 mg/kg 7 gm/70 kg

VESICANTS CONTINUED CONTINUED MUSTARD TOXICITY Blister Death Liquid 10ug 100 mg/kg 7 gm/70 kg VESICANTS 16

VESICANTS 16

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: DAMAGES Skin • Eyes • Airways • Systemic: • – Bone marrow – GI

MUSTARD: DAMAGES

Skin Eyes Airways Systemic:

Bone marrow

GI tract

CNS

Lymphoid tissue

VESICANTS 17

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD CASUALTIES FROM WWI • Eyes ……………………… ... 85% • Respiratory Tract … ... 75%

MUSTARD CASUALTIES FROM WWI

Eyes………………………

...85%

Respiratory Tract… ...75%

Scrotum ………………

.....42%

Face ……………….………

..27%

Anus ……………………….24%

Legs……………… ……….11% ...

Buttocks ……………… Hands ……………

...

.....10%

..4%

………

Feet……………… ...

………1.5%

VESICANTS 18

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: ONSET • Cellular interaction: 1 to 2 minutes • Clinical effects: 2 to 48

MUSTARD: ONSET

Cellular interaction: 1 to 2 minutes

Clinical effects: 2 to 48 hours Usually 4 to 8 hours

VESICANTS 19

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: SKIN • Erythema • Small vesicles; later coalesce • Blisters/bulla • Possible coagulation necrosis

MUSTARD: SKIN

Erythema

Small vesicles; later coalesce

Blisters/bulla

Possible coagulation necrosis with liquid exposure

VESICANTS 20

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: ONSET • Chemical cell damage: 1 to 2 minutes • Clinical effects: 2 to

MUSTARD: ONSET

Chemical cell damage:

1 to 2 minutes

Clinical effects:

2 to 48 hours

Usually 4 to 8 hours

VESICANTS 21

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: EYE • Mild: conjunctivitis, blepharospasm • Moderate: lid inflammation and edema, blepharospasm, corneal roughening

MUSTARD: EYE

Mild: conjunctivitis, blepharospasm

Moderate: lid inflammation and edema, blepharospasm, corneal roughening

Severe: Corneal opacification, ulceration, and/or perforation

VESICANTS 22

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

 

CONTINUED

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

VESICANTS

VESICANTS MUSTARD: ACUTE EFFECTS • Upper airway – Hemorrhage – Pain • Larynx – Hoarseness –

MUSTARD: ACUTE EFFECTS

Upper airway

Hemorrhage

Pain

Larynx

Hoarseness Stridor

VESICANTS 24

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

 

CONTINUED

CONTINUED

 

MUSTARD: ACUTE EFFECTS

Trachea/bronchi

bronchospasm pseudomembranes

Small airway and alveoli (massive exposure)

hemorrhagic edema

VESICANTS 25

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: DEATH • Usually pulmonary: – Damaged airways – Infection – Depressed immune system –

MUSTARD: DEATH

Usually pulmonary:

Damaged airways

Infection

Depressed immune system

Sepsis

VESICANTS 26

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: MARROW • Damaged stem cells • Decreased WBC, RBC, platelets (Day 7 to day

MUSTARD: MARROW

Damaged stem cells

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

Survival rare if WBC <200 (Iran / Iraq)

VESICANTS 27

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: GI • Early (< 24 hours): – transient symptoms – cholinergic effect • Late

MUSTARD: GI

Early (< 24 hours):

transient symptoms

cholinergic effect

Late (>3 days):

severe damage

cytotoxic effect

VESICANTS 28

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS SEVERE MUSTARD EXPOSURE • CNS – Apathy, lethargy – Euphoria – Convulsions, only with massive

SEVERE MUSTARD EXPOSURE

CNS

Apathy, lethargy Euphoria Convulsions, only with massive exposure! Coma Death

VESICANTS 29

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD • Radiomimetic (DNA) – epithelial cells (eye, pulmonary, skin, GI) – hematopoetic – damages

MUSTARD

Radiomimetic (DNA)

epithelial cells

(eye, pulmonary, skin, GI)

hematopoetic

damages many tissues

VESICANTS 30

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: SYMPTOMS • Symptoms within 4 hours = severe injury • Airway symptoms within 6

MUSTARD: SYMPTOMS

Symptoms within 4 hours = severe injury

Airway symptoms within 6 hours is often fatal

VESICANTS 31

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS DIFFERENTIAL DIAGNOSIS • Isolated cases: plant, animal, other chemicals • Many cases: – Latent effects:

DIFFERENTIAL DIAGNOSIS

Isolated cases: plant, animal, other chemicals

Many cases:

Latent effects: Mustard

Immediate effects: Lewisite, Phosgene Oxime

VESICANTS 32

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: DIAGNOSTICS • Non-specific • CBC • Early chemical pneumonitis: fever, WBC, chest x-ray •

MUSTARD: DIAGNOSTICS

Non-specific

CBC

Early chemical pneumonitis:

fever, WBC, chest x-ray

Pneumonia: sputum exam / culture

Urinary thiodiglycol: DA TB Med 296

VESICANTS 33

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: MANAGEMENT Protect Self!!! VESICANTS 34 USAMRICD PROJECT, PROTECT, SUSTAIN

MUSTARD: MANAGEMENT

Protect Self!!!

VESICANTS 34

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS DECONTAMINATION • Early decon protects casualty – within minutes • Late decon protects medical personnel

DECONTAMINATION

Early decon protects casualty within minutes

Late decon protects medical personnel and facility

VESICANTS 35

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MANAGEMENT: SKIN • Soothing cream/lotion • Unroof large blisters • Debridement of burns • Frequent

MANAGEMENT: SKIN

Soothing cream/lotion Unroof large blisters Debridement of burns Frequent irrigation Antibiotics: Topical / Systemic (cellulitis) Systemic analgesics Appropriate IV fluids and electrolytes

VESICANTS 36

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MANAGEMENT: EYES • Soothing eye drops • Topical mydriatics • Topical antibiotics • Vaseline on

MANAGEMENT: EYES

Soothing eye drops Topical mydriatics Topical antibiotics Vaseline on lid edges Avoid topical analgesics Topical steroids - ?? Sunglasses

VESICANTS 37

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MANAGEMENT: AIRWAYS • Steam, cough suppressants • Oxygen • Bronchodilators, steroids • Early intubation •

MANAGEMENT: AIRWAYS

Steam, cough suppressants Oxygen Bronchodilators, steroids Early intubation Assisted ventilation Antibiotics AFTER organism identified

VESICANTS 38

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MANAGEMENT: GI • Atropine • Antiemetics • Fluid therapy • Electrolyte replacement VESICANTS 39 USAMRICD

MANAGEMENT: GI

Atropine

Antiemetics

Fluid therapy

Electrolyte replacement

VESICANTS 39

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MANAGEMENT: MARROW • Blood component replacement – RBC, WBC, Platelets • Marrow transplants • Hormonal

MANAGEMENT: MARROW

Blood component replacement

RBC, WBC, Platelets

Marrow transplants

Hormonal therapy

Reverse isolation

VESICANTS 40

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: LONG TERM • Carcinogen / mutagen • No evidence of human reproductive toxicity •

MUSTARD: LONG TERM

Carcinogen / mutagen

No evidence of human reproductive toxicity

Chronic exposure

Respiratory cancer

Unclear: chronic bronchitis, emphysema

VESICANTS 41

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS MUSTARD: LONG TERM • No evidence of cancer after one or two exposures • Chronic

MUSTARD: LONG TERM

No evidence of cancer after one or two exposures

Chronic eye problems / damage may follow severe eye exposure

VESICANTS 42

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS LEWISITE • World War I origin; not used • Possible use by Japan vs China

LEWISITE

World War I origin; not used

Possible use by Japan vs China

No other known use

Sparse data

VESICANTS 43

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

 

CONTINUED

CONTINUED

 

LEWISITE

Oily, amber to brown liquid

Freezing point ~ 0°F

Heavier than air, water

Persistent

Geranium odor

VESICANTS 44

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

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

LEWISITE: TOXICITY

Vapor

Eyes Effects 2 mg-min/m3

Vesication Death

Liquid

1,500 mg-min/m3 1,500 mg-min/m3

Blister

14 mmg

2.8 g

Death

VESICANTS 45

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS LEWISITE: MECHANISM • Contains arsenic – carcinogen ?? • Reacts with many constituents: cellular necrosis

LEWISITE: MECHANISM

Contains arsenic

carcinogen ??

Reacts with many constituents: cellular necrosis

Mechanism unknown

VESICANTS 46

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS LEWISITE: DAMAGES • Eyes • Skin • Airways • Capillaries VESICANTS 47 USAMRICD PROJECT, PROTECT,

LEWISITE: DAMAGES

Eyes

Skin

Airways

Capillaries

VESICANTS 47

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

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

LEWISITE: TIME OF ONSET

Pain, irritation within 1 min

Tissue necrosis within 5 min

VESICANTS 48

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS LEWISITE: SKIN • Progresses to blister • More necrosis than from mustard VESICANTS 49 USAMRICD

LEWISITE: SKIN

Progresses to blister

More necrosis than from mustard

VESICANTS 49

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS LEWISITE: EYES • Pain, blepharospasm on contact • Rapid edema of conjunctiva, lids – Eyes

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

VESICANTS

VESICANTS LEWISITE: AIRWAYS • Severe irritation • Bronchial epithelial necrosis, similar to mustard • More prone

LEWISITE: AIRWAYS

Severe irritation

Bronchial epithelial necrosis, similar to mustard

More prone to pseudomembranes, pulmonary edema than mustard

VESICANTS 51

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS LEWISITE SHOCK • Increased capillary permeability – Plasma volume decreased – Hemoconcentration – Hypotension –

LEWISITE SHOCK

Increased capillary permeability

Plasma volume decreased Hemoconcentration Hypotension Pulmonary edema Circulatory failure Death

VESICANTS 52

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS LEWISITE: MANAGEMENT • Immediate decontamination • Treat as mustard lesion • British Anti-lewisite (BAL) Dimercaprol

LEWISITE: MANAGEMENT

Immediate decontamination Treat as mustard lesion British Anti-lewisite (BAL) Dimercaprol

Systemic Topical Ophthalmic

VESICANTS 53

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS LEWISITE: TREATMENT • Hospital care - severe exposure – IM injection of BAL (10% in

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

VESICANTS 54

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS BAL SIDE EFFECTS • Lacrimation • Constriction of throat • GI cramps, vomiting, nausea •

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

VESICANTS

VESICANTS PHOSGENE OXIME (CX) • Rapid onset • Toxic, irritating, corrosive • Urticant, not vesicant •

PHOSGENE OXIME (CX)

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

VESICANTS 56

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS PHOSGENE OXIME (CX) • Phosgene oxime corrosive to all tissues (skin, lungs, eyes) – Pulmonary

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 57

USAMRICD

PROJECT, PROTECT, SUSTAIN

VESICANTS

VESICANTS PHOSGENE OXIME: MANAGEMENT • Management: – Symptomatic – Supportive – Same as mustard VESICANTS 58

PHOSGENE OXIME: MANAGEMENT

Management:

Symptomatic

Supportive

Same as mustard

VESICANTS 58

USAMRICD

PROJECT, PROTECT, SUSTAIN

MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES

SUMMARY ANY QUESTIONS?

U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE

MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES SUMMARY ANY QUESTIONS? U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE

USAMRICD

PROTECT, PROJECT, SUSTAIN

MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES SUMMARY ANY QUESTIONS? U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE