What Agent Caused More Chemical Casualties in World

What Agent Caused More Chemical Casualties in World War I Than All Other Chemical Agents Combined?

What chemical agent caused over 5000 known casualties as recently as the 1980's and was also used on civilian populations including children?

What chemical agent is in the arsenals of at least a dozen countries around the globe and ready to use against a perceived enemy?

MUSTARD Clifton E. Yu, MD LTC, MC Department of Pediatrics 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 4

Vesicants Agent that causes vesicles or blisters Ø Main vesicant in production today: sulfur mustard Ø Lewisite and Phosgene Oxime (CX) also classified as vesicants--lesser availability and history of use Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 5

Mustard--Why So Important? No antidote Ø Causes lots of morbidity Ø Relatively easy to synthesize Ø Delayed symptoms Ø Children more susceptible to its toxic effects Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 6

History 1000 B. C. --arsenic smokes used by Chinese against invading Mongol tribes Ø 423 B. C. --Spartans used burning sulfur and coal smoke to attack Athenians in Peloponnesian War Ø 1854 --sulfur mustard first synthesized Ø 1917 --chlorine, phosgene, and particularly mustard used by both British and Germans resulting in thousands of casualties Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 7

10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 8

History (cont. ) 1934 --nitrogen mustard synthesized Ø 1935 --used by Italy against Abyssinia Ø 1937 --Japan allegedly uses mustard gas against China during invasion of Manchuria Ø 1960's--used by Egypt against Yemen Ø 1980's--extensive use of mustard gas against Iranian soldiers and civilians during Iran-Iraq War Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 9

Characteristics of Chemical Agents Ø Volatility--degree to which a substance vaporizes Ø Persistence--refers specifically to how long the substance stays in the environment and is inversely related to volatility 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 10

Characteristics of Mustard Oily, yellow to dark brown liquid Ø Garlic or mustard odor Ø Considered a persistent agent Ø Is "radiomimetic" Ø Thought to work as an alkylating agent Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 11

Detection Smell Ø M 8, M 9 paper, various detectors Ø Clinical recognition Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 12

Clinical Effects Ø Skin, Eyes, Respiratory Tract Ø Bone Marrow, GI, CNS in Severe Exposures 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 13

Skin Effects Latent period of several hours after exposure Ø Erythema, then blister formation Ø With high dose, skin sloughing Ø Blister fluid not hazardous Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 14

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10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 16

Ocular Effects Most often caused by vapor Ø Conjunctival inflammation Ø Corneal damage Ø Severe lid edema Ø Rarely permanent blindness Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 17

Respiratory Effects Vapor induced Ø Upper respiratory tract irritation Ø Dyspnea and productive cough Ø Severe necrotizing tracheobronchitis with pseudomembrane formation Ø Secondary bacterial infection Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 18

Bone Marrow Ø Involvement occurs in severe cases Ø Usually occurs on day 3 to 5 Ø ANC less than 500 or a precipitous drop portends a high risk of sepsis and death 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 19

GI Tract Usually manifested by nausea and vomiting Ø Generally transient and not severe Ø Thought to be caused by cholinergic activity of mustard Ø Delayed nausea and vomiting thought secondary to generalized cytotoxic activity and mucosal damage to GI tract Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 20

CNS Symptoms not usually prominent Ø Common complaints in World War I were apathy, depression, and intellectual dullness Ø 83% of hospitalized Iranians in one study had CNS complaints--usually mild and nonspecific Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 21

Treatment Ø Ø Decon, Decon !!! -only effective means of preventing or decreasing tissue damage -must be performed before entry into a clean MTF Remainder of treatment depends on the other organ systems involved 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 22

Skin Treat like a burn Ø Erythema treated with soothing lotion, e. g. calamine Ø Carefully unroof larger blisters Ø Irrigation of denuded areas 3 -4 X daily Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 23

Skin (cont. ) Topical antibiotics, e. g. Silvedene Ø Systemic antipruritics Ø Systemic analgesics Ø Fluids and electrolytes Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 24

Eyes Thorough irrigation Ø Cycloplegics (e. g. homatropine) Ø Topical antibiotics Ø Vaseline to edges of eyelids Ø Systemic analgesics (e. g. NSAID's) Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 25

Pulmonary Ø Ø Ø Upper airway symptoms--steam inhalation, cough suppressants Avoid using antibiotics early on Intubation if lower resp. sx's progress -attempt before laryngospasm or significant edema develop -direct laryngoscopy with suctioning if evidence of pseudomembrane formation 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 26

Pulmonary (cont. ) Ø No evidence steroids beneficial routinely Ø Prolonged assisted or controlled ventilation-bad prognosis 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 27

Bone Marrow Ø If neutropenic, some advocate gut sterilization with non-absorbable antibiotics Ø Bone marrow transplant or transfusion--may be life-saving in selected cases 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 28

GI Ø Atropine (0. 4 to 0. 6 mg IM or IV for adults) or another anti-cholinergic may be helpful Ø IV fluids 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 29

Summary Decontamination Ø Treat like a burn patient Ø Liberal use of analgesics Ø Fluids and electrolytes (less than for standard burns) Ø System specific treatment as necessary Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 30

But What About Children? Very little in literature Ø Recent experience with childhood mustard exposure from Iran-Iraq War (Momeni and Aminjarahari, Int. J. Derm. Vol 33, March 1994) Ø Earlier onset of skin lesions, more severe Ø More frequent and severe opthalmic, pulmonary, and GI involvement Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 31

Skin Earlier lesions, more bullae Ø First index case may therefore be a child Ø Traditional decontamination with sodium hypochlorite (bleach) may be harmful to child's skin Ø Use copious amounts of soap and water instead Ø 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 32

Eyes Ø More frequent and severe eye findings Ø Same therapeutic interventions 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 33

Pulmonary Ø Higher incidence of lung involvement Ø Increased minute ventilation in children Ø May have to intubate sooner 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 34

GI Ø Increased involvement probably dose related Ø Children more likely to have protracted emesis Ø Atropine or other anti-cholinergic in ageappropriate doses may be helpful 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 35

Pediatric Exposure--Summary Ø Ø Earlier and more severe skin lesions (soap and water for decontamination) Pay early attention to eyes in virtually all children Be on lookout for earlier and more severe lung involvement May have to treat GI symptoms more aggressively (and watch for increase in dehydration) 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 36

BE PREPARED!!! …and get ready for inhalants next week 10/24/2021 Clifton Yu, MD Department of Pediatrics Walter Reed Army Medical Center 37