Weapons of Mass Weapons of Mass DestructionDestruction

Rosen Chapt 195Rosen Chapt 195

May 17, 2007May 17, 2007

Roy Seitz, M.D.Roy Seitz, M.D.

slides byslides by

Scott Gunderson PGY-3Scott Gunderson PGY-3

Nuclear & Nuclear & Radiological Radiological

EventsEvents

Potential Nuclear/Radiological Potential Nuclear/Radiological Hazards in the U.S.Hazards in the U.S.

Simple Radiological DeviceSimple Radiological Device

““Dirty” Conventional Bomb Dirty” Conventional Bomb

Improvised Nuclear Device (IND)Improvised Nuclear Device (IND)

1kT “Suitcase Nuke”1kT “Suitcase Nuke”

Ballistic Missile AttackBallistic Missile Attack

250 kT Nuclear Weapon – “City Killer”250 kT Nuclear Weapon – “City Killer”

Radiation DispersalRadiation Dispersal

““Dirty bombs”Dirty bombs”Low level Low level contaminationcontaminationAcute radiation Acute radiation casualties are casualties are unlikelyunlikelyDecontamination Decontamination and clean up are and clean up are main issuesmain issues

Texas Motor SpeedwayTexas Motor SpeedwayExercise, November 2004Exercise, November 2004

Three critical gaps identified:Three critical gaps identified: Casualty / Patient TriageCasualty / Patient Triage

Medical Decontamination (Med Decon)Medical Decontamination (Med Decon)

Personal Protective Equipment (PPE)Personal Protective Equipment (PPE)

“We may have lost up to 100 one-kiloton suitcase sized nuclear bombs”

-Alexander Lebed

(Former) Chief, National Security, USSR

Diversion of Nuclear WeaponsDiversion of Nuclear Weapons

Energy PartitionEnergy PartitionEnergy PartitionEnergy Partition

Initial Radiation

5%

Thermal 35%

Blast 50%

Fallout10%

Initial Radiation

5%

Thermal 35%

Blast 50%

Fallout10%

Standard Fission / FusionStandard Fission / FusionStandard Fission / FusionStandard Fission / Fusion

AFRRI, AFRRI, Medical Effects of Nuclear WeaponsMedical Effects of Nuclear Weapons, “Blast and Thermal Effects” Lecture, 1990., “Blast and Thermal Effects” Lecture, 1990.

Scenario: Washington Scenario: Washington MallMall

AFRRI, AFRRI, Medical Effects of Nuclear WeaponsMedical Effects of Nuclear Weapons, “Blast and Thermal Effects” Lecture, 1990., “Blast and Thermal Effects” Lecture, 1990.

Effective Range For Thermal Effective Range For Thermal EnergyEnergy

1 kT Weapon1 kT Weapon

Effective Range For Thermal Effective Range For Thermal EnergyEnergy

1 kT Weapon1 kT Weapon

AFRRI, AFRRI, Medical Effects of Nuclear WeaponsMedical Effects of Nuclear Weapons, “Blast and Thermal Effects” Lecture, 1990., “Blast and Thermal Effects” Lecture, 1990.

AFRRI, AFRRI, Medical Effects of Nuclear WeaponsMedical Effects of Nuclear Weapons, “Blast and Thermal Effects” Lecture, 1990., “Blast and Thermal Effects” Lecture, 1990.

Atlanta SSE Med Wind 250Kton FatalitiesAtlanta SSE Med Wind 250Kton Fatalities

Atlanta 250 kiloton SSE windAtlanta 250 kiloton SSE wind 7mph7mph

Mortality Probability 3.9m Affected

Red 90% Dark Blue 40%

Lt Brown 80% Lt Purple 30%

Yellow 70% Dk Purple 20%

Green 60% Dk Pink 10%

Pale Blue 50% Lt Pink 1%

New York New York City – 250 City – 250 kT Nuclear kT Nuclear DetonationDetonation

What is Fallout?What is Fallout?What is Fallout?What is Fallout?

A complex mixture of over 200 different A complex mixture of over 200 different isotopes of 36 elementsisotopes of 36 elements

2 oz of fission products formed for each kT of 2 oz of fission products formed for each kT of yield.yield.

Size < 1 micron to several mm.Size < 1 micron to several mm.

A complex mixture of over 200 different A complex mixture of over 200 different isotopes of 36 elementsisotopes of 36 elements

2 oz of fission products formed for each kT of 2 oz of fission products formed for each kT of yield.yield.

Size < 1 micron to several mm.Size < 1 micron to several mm.

Early FalloutEarly FalloutEarly FalloutEarly FalloutReaches the ground during the first 24 hours Reaches the ground during the first 24 hours after detonationafter detonation

Early fallout = 50-70% of total radioactivityEarly fallout = 50-70% of total radioactivity

Highest degree of fallout risk Highest degree of fallout risk

7:10 Rule for estimating exposure7:10 Rule for estimating exposure

HoursHours 11 7 7 49 49

Gy/hr 1 0.1 Gy/hr 1 0.1 0.01 0.01

Reaches the ground during the first 24 hours Reaches the ground during the first 24 hours after detonationafter detonation

Early fallout = 50-70% of total radioactivityEarly fallout = 50-70% of total radioactivity

Highest degree of fallout risk Highest degree of fallout risk

7:10 Rule for estimating exposure7:10 Rule for estimating exposure

HoursHours 11 7 7 49 49

Gy/hr 1 0.1 Gy/hr 1 0.1 0.01 0.01

Delayed FalloutDelayed FalloutDelayed FalloutDelayed Fallout

Arrives after 1Arrives after 1stst day day

Very fine / invisible particles Very fine / invisible particles Settle in very low concentrations over most of the earth’s surfaceSettle in very low concentrations over most of the earth’s surface

40% of total radioactivity40% of total radioactivity

Much lower degree of risk relative to early falloutMuch lower degree of risk relative to early fallout

Arrives after 1Arrives after 1stst day day

Very fine / invisible particles Very fine / invisible particles Settle in very low concentrations over most of the earth’s surfaceSettle in very low concentrations over most of the earth’s surface

40% of total radioactivity40% of total radioactivity

Much lower degree of risk relative to early falloutMuch lower degree of risk relative to early fallout

AlphaAlpha

BetaBeta

GammaGamma

1 m Concrete1 m Concrete

NeutronNeutron

Ionizing RadiationIonizing RadiationAny Radiation Consisting of Directly or Indirectly Ionizing Particles or PhotonsAny Radiation Consisting of Directly or Indirectly Ionizing Particles or Photons

Keys to Limiting ExposureKeys to Limiting ExposureShielding Shielding Dense objects limit the amount of radiation that Dense objects limit the amount of radiation that

can get to youcan get to you

Distance Distance Dose decreases rapidlyDose decreases rapidly as you move awayas you move away from the sourcefrom the source

TimeTime Minimizing time spent in proximity to the source Minimizing time spent in proximity to the source

is importantis important

500 R/hr

125

123Feet

5555

Radiation InjuryRadiation Injury

Chemical Damage

Free Radicals

10-10 Seconds

1. Proteins2. Membrane3. DNA

Cellular Damage

Tissue damage & Loss of organ

function

Hours to years

OrganDamage

Seconds to hours

Distribution of Injuries in aDistribution of Injuries in aNuclear DetonationNuclear Detonation

Distribution of Injuries in aDistribution of Injuries in aNuclear DetonationNuclear Detonation

Burns + Irradiation 40%

Wounds < 5%

Burns + Wounds + Irradiation

20%

Irradiation 15 - 20%

Burns 15 - 20%

Wounds + Irradiation

5%

Wounds + Burns

5%

Burns + Irradiation 40%

Wounds < 5%

Burns + Wounds + Irradiation

20%

Irradiation 15 - 20%

Burns 15 - 20%

Wounds + Irradiation

5%

Wounds + Burns

5%Single Injuries

(30% - 40%)Single Injuries

(30% - 40%)

Combined Injuries(65% - 70%)

Combined Injuries(65% - 70%)

Data from Walker RI, Cerveny TJ Eds., Data from Walker RI, Cerveny TJ Eds., Medical Consequences of Nuclear Warfare,Medical Consequences of Nuclear Warfare, TMM Publications, Falls Church, 1989. p 11. TMM Publications, Falls Church, 1989. p 11.

HemogramHemogram(300 cGy TBI Exposure)(300 cGy TBI Exposure)

HemogramHemogram(300 cGy TBI Exposure)(300 cGy TBI Exposure)

Andrews Lymphocyte NomogramAndrews Lymphocyte NomogramAndrews Lymphocyte NomogramAndrews Lymphocyte Nomogram

Absolute Lymphocyte Absolute Lymphocyte Count over 48 hoursCount over 48 hours

Confirms Significant Confirms Significant Radiation ExposureRadiation Exposure

From From Andrews GA, Auxier JA, Lushbaugh CC: The Andrews GA, Auxier JA, Lushbaugh CC: The Importance of Dosimetry to the Medical Importance of Dosimetry to the Medical Management of Persons Exposed to High Levels Management of Persons Exposed to High Levels of Radiation. of Radiation. In In Personal Dosimetry for Radiation Personal Dosimetry for Radiation Accidents. Vienna, International Atomic Energy Accidents. Vienna, International Atomic Energy Agency, 1965, pp 3- 16Agency, 1965, pp 3- 16

From From Andrews GA, Auxier JA, Lushbaugh CC: The Andrews GA, Auxier JA, Lushbaugh CC: The Importance of Dosimetry to the Medical Importance of Dosimetry to the Medical Management of Persons Exposed to High Levels Management of Persons Exposed to High Levels of Radiation. of Radiation. In In Personal Dosimetry for Radiation Personal Dosimetry for Radiation Accidents. Vienna, International Atomic Energy Accidents. Vienna, International Atomic Energy Agency, 1965, pp 3- 16Agency, 1965, pp 3- 16

Primary Treatment StrategyPrimary Treatment StrategyTreat life threatening trauma firstTreat life threatening trauma firstRemove clothing / DecontaminateRemove clothing / DecontaminateTreat radiation effectsTreat radiation effects Burn careBurn care Pharmaceutical therapiesPharmaceutical therapies

If surgery is neededIf surgery is needed first 1-2 days first 1-2 days OROR 50 days post-exposure50 days post-exposure

Decontamination Decontamination EquipmentEquipment

Decontamination Decontamination EquipmentEquipment

Hospital Surgical Gown (waterproof)Hospital Surgical Gown (waterproof)

Cap, Face Shield, Booties (waterproof)Cap, Face Shield, Booties (waterproof)

Double Gloves (inner layer taped)Double Gloves (inner layer taped)

DrapesDrapes

Plastic BagsPlastic Bags

Butcher PaperButcher Paper

Large Garbage CansLarge Garbage Cans

Radiation Signs and TapeRadiation Signs and Tape

Hospital Surgical Gown (waterproof)Hospital Surgical Gown (waterproof)

Cap, Face Shield, Booties (waterproof)Cap, Face Shield, Booties (waterproof)

Double Gloves (inner layer taped)Double Gloves (inner layer taped)

DrapesDrapes

Plastic BagsPlastic Bags

Butcher PaperButcher Paper

Large Garbage CansLarge Garbage Cans

Radiation Signs and TapeRadiation Signs and Tape

Decon AgentsDecon AgentsDecon AgentsDecon Agents

Dry RemovalDry Removal Disrobing is 80% effectiveDisrobing is 80% effective

Soap / Shampoo & WaterSoap / Shampoo & Water

Others ??Others ??

Dry RemovalDry Removal Disrobing is 80% effectiveDisrobing is 80% effective

Soap / Shampoo & WaterSoap / Shampoo & Water

Others ??Others ??

Nuclear SummaryNuclear SummaryNuclear & Radiological Devices Nuclear & Radiological Devices Lots of trauma and burn injuriesLots of trauma and burn injuries ARS and cancersARS and cancers

Care Issues Care Issues Bed Capacity / AvailabilityBed Capacity / Availability Burn & Trauma careBurn & Trauma care Decontamination Decontamination AntidotesAntidotes

Need for extensive planningNeed for extensive planning

Biological Biological WeaponsWeapons

Definition of BioterrorismDefinition of Bioterrorism

Cause harm to humansCause harm to humans

Influence government conductInfluence government conduct

Intimidate or coerce a civilian populationIntimidate or coerce a civilian population

Intentional use of pathogen or bacterial product Intentional use of pathogen or bacterial product to:to:

Bioterrorism Release TypesBioterrorism Release Types

Overt ReleaseOvert Release Notice of release providedNotice of release provided May contain a threatMay contain a threat Designed to create panic or fearDesigned to create panic or fear White powder hoaxesWhite powder hoaxes May be hoax or credible threatMay be hoax or credible threat

Covert ReleaseCovert Release No notice or threatNo notice or threat Difficult to detectDifficult to detect

Biological Biological Agent OverviewAgent Overview

AnthraxAnthrax

Bacillus anthracisBacillus anthracis

Anthrax- GeneralAnthrax- GeneralEndemic in animals worldwide with Endemic in animals worldwide with occasional human cases (usually occasional human cases (usually cutaneous)cutaneous)

Spores used for bioattackSpores used for bioattack Aerosolized directly or sent in Aerosolized directly or sent in

mail/packagesmail/packages

Three formsThree forms Cutaneous, Inhalation, GICutaneous, Inhalation, GI

Anthrax – Clinical FeaturesAnthrax – Clinical Features

InhalationInhalation Incubation: 2-43 days (may be longer)Incubation: 2-43 days (may be longer) Prodrome Prodrome

fevers, malaise, dry cough, chest pain, fevers, malaise, dry cough, chest pain, dyspnea, myalgiadyspnea, myalgia

Abrupt onset of fulminant illnessAbrupt onset of fulminant illness Widened mediastinum, pleural effusions; Widened mediastinum, pleural effusions;

meningitis in ~50%meningitis in ~50% Actual pneumonia uncommonActual pneumonia uncommon

Inhalational anthrax—US index case

Anthrax – Clinical FeaturesAnthrax – Clinical Features

CutaneousCutaneous Incubation: 1 to 7days (may be up to 12 days)Incubation: 1 to 7days (may be up to 12 days) Erythematous papule Erythematous papule ulcer ulcer characteristic characteristic

black eschar with surrounding erythema and black eschar with surrounding erythema and edemaedema

Regional adenopathy and systemic symptoms Regional adenopathy and systemic symptoms (e.g., fever, malaise) may develop(e.g., fever, malaise) may develop

Cutaneous AnthraxCutaneous Anthrax

Anthrax – Clinical FeaturesAnthrax – Clinical Features

GastrointestinalGastrointestinal Incubation period 1-7 daysIncubation period 1-7 days Not likely after a bioattackNot likely after a bioattack Presents as febrile illness with bloody diarrheaPresents as febrile illness with bloody diarrhea

Anthrax DiagnosisAnthrax DiagnosisBlood cultures Blood cultures usually positive in <24husually positive in <24h

Gram stain/Dx of pleural fluid or CSFGram stain/Dx of pleural fluid or CSF

Sputum is usually NOT positive by stain/cultureSputum is usually NOT positive by stain/culture

Fever and widened mediastinum on CXR/CT very Fever and widened mediastinum on CXR/CT very suggestivesuggestive

Cutaneous diseaseCutaneous disease culture fluid from under escharculture fluid from under eschar

Nasal swabs are a poor testNasal swabs are a poor test

Anthrax in CSF—US index case

Anthrax - TreatmentAnthrax - Treatment

Ciprofloxacin 400 mg IV q12hCiprofloxacin 400 mg IV q12h 10-15 mg/kg for children 10-15 mg/kg for children other fluoroquinolones probably also effectiveother fluoroquinolones probably also effective

OROR

Doxycycline 100 mg IV q12hDoxycycline 100 mg IV q12h 2.2 mg/kg for children2.2 mg/kg for children

PLUSPLUS

1 or 2 additional antibiotics1 or 2 additional antibiotics (clindamycin, rifampin, vancomycin, penicillin, (clindamycin, rifampin, vancomycin, penicillin,

chloramphenicol, imipenem, clarithromycin)chloramphenicol, imipenem, clarithromycin)

Switch to oral therapy when clinically Switch to oral therapy when clinically appropriateappropriate 60 days therapy (or until third dose vaccine)60 days therapy (or until third dose vaccine) ciprofloxacin 500 mg PO BID orciprofloxacin 500 mg PO BID or doxycycline 100 mg PO BIDdoxycycline 100 mg PO BID

Anthrax - TreatmentAnthrax - Treatment

Prophylaxis and Infection Prophylaxis and Infection ControlControl

ProphylaxisProphylaxis Ciprofloxacin 500 mg PO BID (10-15 mg/kg for Ciprofloxacin 500 mg PO BID (10-15 mg/kg for

children )children )

oror Doxycycline 100 mg PO BID (2.2 mg/kg for children)Doxycycline 100 mg PO BID (2.2 mg/kg for children) Continue for 60 days (? 100 days)Continue for 60 days (? 100 days) Vaccine available for DOD forcesVaccine available for DOD forces

Infection ControlInfection Control Standard barrier precautions are neededStandard barrier precautions are needed

17

VaccineVaccine

PlaguePlague

Yersinia pestisYersinia pestis

Yersinia pestis Yersinia pestis Source: www.cdc.govSource: www.cdc.gov

Plague - GeneralPlague - GeneralEndemic in animals many parts of the worldEndemic in animals many parts of the world Including prairie dogs in the southwestern usIncluding prairie dogs in the southwestern us

High potential as a BT agent High potential as a BT agent

Endemic form Endemic form Spread to humans via a flea vector Spread to humans via a flea vector Bubonic form of the diseaseBubonic form of the disease

BioattackBioattack Most likely aerosolizedMost likely aerosolized Pneumonic plaguePneumonic plague

Plague – Clinical FeaturesPlague – Clinical Features

Following BioattackFollowing Bioattack 1-6 day incubation1-6 day incubation Abrupt onset Abrupt onset

High feverHigh fever

Chills, malaiseChills, malaise

Cough with bloody sputumCough with bloody sputum

SepsisSepsis Severe rapidly progressive pneumoniaSevere rapidly progressive pneumonia

BuboesBuboes

Bubonic PlagueBubonic Plague

Source: www.cdc.govSource: www.cdc.gov

Plague - DiagnosisPlague - DiagnosisCXR with patchy infiltratesCXR with patchy infiltrates

Culture of blood and sputumCulture of blood and sputum Need to inform the laboratory if you Need to inform the laboratory if you

suspect plaguesuspect plague

Gram stain may show characteristic “safety-Gram stain may show characteristic “safety-pin” bipolar stainingpin” bipolar staining

Yersinia pestis in blood

Source: www.cdc.govSource: www.cdc.gov

PlaguePlague

Plague pneumonia

Plague - TreatmentPlague - TreatmentPreferredPreferred

StreptomycinStreptomycin 1 g IM q12h 1 g IM q12h 15 mg/kg/dose for children15 mg/kg/dose for children Avoid in pregnant womenAvoid in pregnant women

GentamicinGentamicin 5 mg /kg IM or IV qd 5 mg /kg IM or IV qd or 2 mg/kg load the 1.7 mg/kg q8hor 2 mg/kg load the 1.7 mg/kg q8h for children use 2.5 mg/kg q8hfor children use 2.5 mg/kg q8h

AlternativeAlternativeDoxycycline Doxycycline 100 mg IV q12h100 mg IV q12h

2.2 mg/kg/dose q12h for children2.2 mg/kg/dose q12h for children

Ciprofloxacin Ciprofloxacin 400 mg IV q12h 400 mg IV q12h other fluoroquinolones probably effectiveother fluoroquinolones probably effective for children 15 mg/kg/dose q12hfor children 15 mg/kg/dose q12h

Plague - Infection ControlPlague - Infection Control

ProphylaxisProphylaxisDoxycycline 100 mg PO bidDoxycycline 100 mg PO bid 2.2 mg/kg for children2.2 mg/kg for children

Ciprofloxacin 500 mg PO bidCiprofloxacin 500 mg PO bid 20 mg/kg for children20 mg/kg for children other fluoroquinolones probably effectiveother fluoroquinolones probably effective

Treat for 7 daysTreat for 7 days

IsolationIsolationDroplet precautionsDroplet precautions

SmallpoxSmallpox

Source: www.cdc.govSource: www.cdc.gov

Smallpox - GeneralSmallpox - GeneralOne of the deadliest disease knownOne of the deadliest disease known Mortality rate of 30%Mortality rate of 30%

US stopped vaccinating in 1972US stopped vaccinating in 1972

Declared eradicated by WHODeclared eradicated by WHO 19801980

Bioattack Bioattack aerosolized virus or by exposure to purposefully aerosolized virus or by exposure to purposefully

infected terroristsinfected terrorists

Smallpox - Clinical FeaturesSmallpox - Clinical FeaturesIncubation periodIncubation period 7-17 day (average 12d)7-17 day (average 12d)

Severe prodromeSevere prodrome 2-3 day of fever, severe myalgias, prostration, occ. n/v, 2-3 day of fever, severe myalgias, prostration, occ. n/v,

deleriumdelerium 10% with light facial erythematous rash10% with light facial erythematous rash

Distinctive rash Distinctive rash initially on face and extremities initially on face and extremities including palms and solesincluding palms and soles spreads to trunk spreads to trunk

Small Pox - Clinical FeaturesSmall Pox - Clinical Features

Rash Rash macules macules papules papules vesicles vesicles pustules pustules unlike chicken pox, lesions don’t appear in “crops”unlike chicken pox, lesions don’t appear in “crops”

All lesions in area same stage of developmentAll lesions in area same stage of development

Lesions are firm, deep, frequently umbilicatedLesions are firm, deep, frequently umbilicated

Rash scabs over in 1-2 weeksRash scabs over in 1-2 weeks scars after scabs separatescars after scabs separate

SmallpoxSmallpoxSource: www.cdc.govSource: www.cdc.gov

Smallpox vs. ChickenpoxSmallpox vs. Chickenpox

ChickenpoxChickenpox

SmallpoxSmallpoxSource: www.cdc.govSource: www.cdc.gov

Smallpox DiagnosisSmallpox Diagnosis

Clinical recognition essentialClinical recognition essential

All patients with disseminated vesicular/pustular rash All patients with disseminated vesicular/pustular rash should be screenedshould be screened

Notify public health authorities on clinical Notify public health authorities on clinical suspicion alone, suspicion alone, beforebefore diagnosis is confirmed diagnosis is confirmed

Confirmatory tests available at CDCConfirmatory tests available at CDC

SmallpoxSmallpox

Source: www.cdc.govSource: www.cdc.gov

SmallpoxSmallpoxThe main diagnostic tool for smallpoxThe main diagnostic tool for smallpox

Source: www.cdc.govSource: www.cdc.gov

is the history and physical!is the history and physical!

Smallpox - TreatmentSmallpox - TreatmentVaccinationVaccination in the early stages of diseasein the early stages of disease

Supportive careSupportive care Penicillinase-resistant antibiotics (for secondary Penicillinase-resistant antibiotics (for secondary

infection)infection) Daily eye rinsing Daily eye rinsing Adequate hydration and nutritionAdequate hydration and nutrition

No specific therapy has been FDA approved.No specific therapy has been FDA approved. Topical idoxuridine for corneal lesions Topical idoxuridine for corneal lesions Cidofovir?Cidofovir?

Smallpox - Infection ControlSmallpox - Infection Control

ProphylaxisProphylaxis Vaccine is effective if given within 3 days of Vaccine is effective if given within 3 days of

exposureexposureIsolationIsolation

Airborne and contact precautionsAirborne and contact precautionsFebrile illness after potential exposure should prompt Febrile illness after potential exposure should prompt isolation isolation beforebefore rash starts rash starts

Immediate contact your hospital Immediate contact your hospital epidemiologist and the public health epidemiologist and the public health authoritiesauthorities

Viral Hemorrhagic FeversViral Hemorrhagic Fevers

Ebola virusEbola virusSource: www.cdc.govSource: www.cdc.gov

VHF - GeneralVHF - GeneralNaturally occurring disease Naturally occurring disease Transmitted to humans by contact with infected animals or Transmitted to humans by contact with infected animals or

arthropod vectors.arthropod vectors. Sporadic outbreaks in Africa,parts of Asia and EuropeSporadic outbreaks in Africa,parts of Asia and Europe

VHF viruses as bioterrorism agentsVHF viruses as bioterrorism agents Weaponized by several counties Weaponized by several counties AerosolizationAerosolization

Case fatality ratesCase fatality rates Omsk hemorrhagic feverOmsk hemorrhagic fever 0.5%0.5% EbolaEbola 90%90%

VHF - Clinical FeaturesVHF - Clinical FeaturesIncubation 2 - 21days Incubation 2 - 21days Depends on virusDepends on virus

Initial presentationInitial presentation Nonspecific prodrome (fever, myalgias, headache, Nonspecific prodrome (fever, myalgias, headache,

abdominal pain, prostration)abdominal pain, prostration) Exam may show only flushing of face and chest, Exam may show only flushing of face and chest,

conjunctival injection, and petechiaeconjunctival injection, and petechiae

Disease progresses to shock and generalized Disease progresses to shock and generalized mucous membrane hemorrhagemucous membrane hemorrhage

VHF - DiagnosisVHF - DiagnosisClinical presentationClinical presentation thrombocytopenia, leukopenia, AST elevation thrombocytopenia, leukopenia, AST elevation

commoncommon

Definitive diagnosis requires detection of Definitive diagnosis requires detection of antigens or antibodiesantigens or antibodies testing done at CDCtesting done at CDC

Do Do notnot wait to confirm the diagnosis before wait to confirm the diagnosis before notifying the local public health authoritiesnotifying the local public health authorities

VHF - TreatmentVHF - Treatment

Supportive careSupportive care

Ribavirin may be usefulRibavirin may be useful adults and children: 30 mg/kg IV load (max 2 adults and children: 30 mg/kg IV load (max 2

g) g) then 16 mg/kg (max 1g) q6h x 4 daysthen 16 mg/kg (max 1g) q6h x 4 days

then 8 mg/kg (max 500 mg) IV q8h for 6 daysthen 8 mg/kg (max 500 mg) IV q8h for 6 days an oral dosing regimen is also availablean oral dosing regimen is also available

VHF - Infection ControlVHF - Infection ControlProphylaxisProphylaxis: None at this time: None at this time

IsolationIsolation Blood and bodily fluids Blood and bodily fluids extremelyextremely infectious infectious Liquid-impervious protective coverings, including leg Liquid-impervious protective coverings, including leg

and shoe coveringsand shoe coverings Double glovesDouble gloves N-95 or better respiratorsN-95 or better respirators Face shields or gogglesFace shields or goggles Negative pressure roomNegative pressure room

Chemical Chemical AgentsAgents

History: World War IHistory: World War IFirst large-scale useFirst large-scale use

Ypres, BelgiumYpres, Belgium April 1915April 1915 Chlorine, 168 tonsChlorine, 168 tons 5,000 deaths5,000 deaths 5 mile front5 mile front

Chemical Casualties in WWIChemical Casualties in WWI

9,0009,000191,000191,000GermanyGermany

3,0003,00097,00097,000Austria-Austria-HungaryHungary

1,4621,46271,34571,345U.S.U.S.4,6274,62755,37355,373ItalyItaly

56,00056,000419,340419,340RussiaRussia8,0008,000182,000182,000FranceFrance8,1098,109180,597180,597BritainBritain

DeathsDeathsNon-fatalNon-fatalCountryCountry

Potential Potential Chemical AgentsChemical Agents

Mustards, LewisiteMustards, LewisiteVessicantsVessicants

BZ, Others?BZ, Others?Incapacitating Incapacitating agentsagents

Phosgene, chlorine, Phosgene, chlorine, ammonia, pepper sprayammonia, pepper spray

Irritant Irritant AgentsAgents

CyanidesCyanidesBlood AgentsBlood AgentsTabun, Sarin, Soman, VXTabun, Sarin, Soman, VXNerve AgentsNerve Agents

Nerve AgentsNerve Agents

Nerve AgentsNerve Agents• OrganophosphatesOrganophosphates

• Are similar to Are similar to insecticides:insecticides:– MalathionMalathion– DiazinonDiazinon– Chlorpyrifos Chlorpyrifos

SarinSarin

SomanSomanTabunTabun

VXVX

Nerve Agent PathophysiologyNerve Agent Pathophysiology

AcetylcholineAcetylcholine Neurotransmitter Neurotransmitter

parasympathetic parasympathetic nervous systemnervous system

Neuromuscular endplateNeuromuscular endplate GangliaGanglia

SympatheticSympatheticparasympatheticparasympathetic

AChEAChE

AChACh

Ach Ach ReceptorReceptor

AChEAChE

AChACh

Nerve Nerve AgentAgent

Nerve Agents Nerve Agents Signs and Symptoms Signs and Symptoms

DD - defecation- defecation

U – urinationU – urination

M – miosis (pinpoint pupils)M – miosis (pinpoint pupils)

B – BRONCHORRHEA, BRONCHOSPASMB – BRONCHORRHEA, BRONCHOSPASM

E – emesis (vomiting)E – emesis (vomiting)

L – lacrimation (watery eyes)L – lacrimation (watery eyes)

S – secretionsS – secretions

Muscarinic toxidromeMuscarinic toxidrome

Nerve Agent Nerve Agent Signs & SymptomsSigns & Symptoms

Days of the weekDays of the week M: mydriasis (pupil dilation)M: mydriasis (pupil dilation) T: tachycardiaT: tachycardia W: weaknessW: weakness tH: hypertensiontH: hypertension F: fasciculationsF: fasciculations

Nicotinic toxidromeNicotinic toxidrome

Nerve agent exposureNerve agent exposure

Low exposureLow exposure Miosis, dim vision, eye painMiosis, dim vision, eye pain RhinorrheaRhinorrhea DyspneaDyspnea Localized sweating & fasiciulation (liquids)Localized sweating & fasiciulation (liquids)

High exposureHigh exposure Immediate loss of consciousnessImmediate loss of consciousness SeizuresSeizures ApneaApnea Flaccid paralysisFlaccid paralysis

Vapor – effects occur within secondsVapor – effects occur within secondsLiquids – onset may be delayedLiquids – onset may be delayed

Nerve Agent-TriageNerve Agent-Triage

Tokyo SarinTokyo Sarin 3/6 victims in cardiac arrest resuscitated3/6 victims in cardiac arrest resuscitated Majority were worried wellMajority were worried well

Consider Consider cardiaccardiacarrest as arrest as immediate?immediate?

Nerve Agents: TreatmentNerve Agents: Treatment

• ABC’s, supportive careABC’s, supportive care

• AntidotesAntidotes–Atropine Atropine

• 2 mg IV, IM or ET2 mg IV, IM or ET

–Pralidoxine (2-PAM)Pralidoxine (2-PAM)• 1 gram slow IV or Mark I kit IM (600 mg)1 gram slow IV or Mark I kit IM (600 mg)

– Benzodiazepines, PRN for seizuresBenzodiazepines, PRN for seizures

AChEAChEAChACh

Nerve Nerve AgentAgent

AtropineAtropine

2 PAM2 PAM

MuscarinicMuscarinicNicotinicNicotinic

ReceptorsReceptors

Nerve Agent TreatmentNerve Agent TreatmentAtropine Starting dose - 2 mgAtropine Starting dose - 2 mg

Maximum cumulative dose - 20 mgMaximum cumulative dose - 20 mg Insecticide poisoning requires moreInsecticide poisoning requires more

Atropine – How much to give?Atropine – How much to give? Until secretions are drying or dryUntil secretions are drying or dry Until ventilation is easyUntil ventilation is easy If conscious or comfortableIf conscious or comfortable Do not rely on heart rate or pupil sizeDo not rely on heart rate or pupil size

Irritant GassesIrritant GassesCombine with moisture to Combine with moisture to form acids or basesform acids or bases

Low concentrationLow concentration Minor irritationMinor irritation

High concentrationHigh concentration Chemical burnsChemical burns

Irritant Gas - SymptomsIrritant Gas - SymptomsExcess mucous Excess mucous productionproductionConjunctivitisConjunctivitisCoughing & DysphoniaCoughing & DysphoniaStridor and aphoniaStridor and aphoniaBronchospasm Bronchospasm Shortness of breathShortness of breathNon- cardiogenic Non- cardiogenic pulmonary edemapulmonary edema

LowerLower

ConcentrationConcentration

Higher ConcentrationHigher Concentration

Or Prolonged ExposureOr Prolonged Exposure

Highly Water Soluble Highly Water Soluble Irritant GasesIrritant Gases

AmmoniaAmmonia

FormaldehydeFormaldehyde

Hydrogen Chloride Hydrogen Chloride

Sulfur DioxideSulfur Dioxide

Mostly upper airway to vocal cordsMostly upper airway to vocal cords laryngospasmlaryngospasm

Moderately Water Soluble Moderately Water Soluble Irritant GasesIrritant Gases

ChlorineChlorine Hydrochloric acid Hydrochloric acid Hypochlorus acidHypochlorus acid Greenish-yellow gasGreenish-yellow gas

Slightly slower to combine with waterSlightly slower to combine with water

Affects upper & lower airwaysAffects upper & lower airways

Poorly Water Soluble Poorly Water Soluble Irritant GasesIrritant Gases

Phosgene (COClPhosgene (COCl22)) Forms hydrochloric acidForms hydrochloric acid

Nitrogen dioxide (NONitrogen dioxide (NO22)) Forms nitric acidForms nitric acid

Inhaled into alveoli before combining with Inhaled into alveoli before combining with waterwater

Results in pulmonary edema Results in pulmonary edema Onset often delayed (20 min to 24 hrs)Onset often delayed (20 min to 24 hrs)

Phosgene (CG)Phosgene (CG)Most dangerous of pulmonary agentsMost dangerous of pulmonary agents Developed as warfare agent, first use 1917Developed as warfare agent, first use 1917 > 1 billion pounds/yr for industrial uses> 1 billion pounds/yr for industrial uses

Poor Warning PropertiesPoor Warning Properties Odor of New Mown HayOdor of New Mown Hay

Accumulates in low areas (trenches)Accumulates in low areas (trenches)Initial presence/absence of symptoms do Initial presence/absence of symptoms do not predict severity of exposurenot predict severity of exposure

Irritant Gases: TreatmentIrritant Gases: Treatment

Dry decontamination usually adequateDry decontamination usually adequate

Water for mucous membrane irritationWater for mucous membrane irritation

ABC’s & Oxygen PRNABC’s & Oxygen PRN

Early airway management Early airway management highly and moderately water soluble exposureshighly and moderately water soluble exposures

Inhaled beta agonist PRN wheezingInhaled beta agonist PRN wheezing

Observation and support Observation and support phosgene 12- 24 hrs?phosgene 12- 24 hrs?

Cyanide (AC, CK)Cyanide (AC, CK)Formerly referred to as “blood agents”Formerly referred to as “blood agents”

Odor “bitter almonds”? – “musty” smellOdor “bitter almonds”? – “musty” smell

Odor not a reliable indicator (genetic)Odor not a reliable indicator (genetic)

Inhibits Oxygen Utilization (bright red Inhibits Oxygen Utilization (bright red venous blood)venous blood)

Cyt c Cyt a cyt a3+ Cu

ADP ATP

O2 + H+

H20

OO22

OO22 OO22

OO22

Cyanide - SourcesCyanide - Sources

Pits of many plantsPits of many plants Cherries, peaches, almonds, lima beansCherries, peaches, almonds, lima beans Cassava plant rootCassava plant root

Combustion of carbon -> cyanideCombustion of carbon -> cyanide Plastics- acrylonitrilesPlastics- acrylonitriles

U.S. sources manufacture 300,000 tons of U.S. sources manufacture 300,000 tons of hydrogen cyanide annuallyhydrogen cyanide annually

Cyanide TreatmentCyanide Treatment

Remove to Fresh AirRemove to Fresh AirOxygen, supportive careOxygen, supportive careAntidotesAntidotes

Cyanide AntidotesCyanide AntidotesStep 1Step 1 Amyl nitrite Amyl nitrite

inhale 30 sec/min until IV)inhale 30 sec/min until IV)

Step 2Step 2 Sodium nitriteSodium nitrite

10 ml of 3% IV over 5-10 minutes10 ml of 3% IV over 5-10 minutes

Step 3Step 3 Sodium thiosulfateSodium thiosulfate

50ml of 25% IV over 20 minutes50ml of 25% IV over 20 minutes

Fe2+Hb

Fe3+MetHb

Amyl Nitrite

Sodium Nitrite

Fe3+

Sodium Thiosulfate

ThiocyanateExcreted in urine

Fe3+ Cyt a3

Blister Agents/VesicantsBlister Agents/Vesicants

Sulfur & Nitrogen mustardSulfur & Nitrogen mustard LewisiteLewisite

Vesicant SymptomsVesicant Symptoms

Onset of symptoms ?Onset of symptoms ?

Topical – Eyes, Airway, SkinTopical – Eyes, Airway, Skin

Binds Irreversibly within minutes Binds Irreversibly within minutes “Fixing”“Fixing”

Systemic effects ?Systemic effects ?

Vesicant MechanismsVesicant MechanismsMustardsMustards

Penetrates cells and Penetrates cells and generates toxic generates toxic intermediateintermediate

Alkylates Alkylates DNA/RNA, ProteinsDNA/RNA, Proteins

Rapidly dividing cells Rapidly dividing cells most susceptiblemost susceptible

LewisiteLewisite

Immediate irritant/caustic Immediate irritant/caustic effecteffect

As uncouples oxidative As uncouples oxidative phosphorylationphosphorylation Impairs energy productionImpairs energy production

Vesicant TreatmentVesicant Treatment

Immediate decontamination (2 minutes)Immediate decontamination (2 minutes)

Victim may not undergo decontamination Victim may not undergo decontamination since symptoms delayedsince symptoms delayed

Remove clothes and wash skin with soap and Remove clothes and wash skin with soap and waterwater

Avoid overhydration; fluid losses less than Avoid overhydration; fluid losses less than with thermal burnswith thermal burns

Lewisite TreatmentLewisite TreatmentBritish Anti-Lewisite (BAL)British Anti-Lewisite (BAL) Chelating agentChelating agent Topical application for decontaminationTopical application for decontamination Administer IM to victims with shock or severe Administer IM to victims with shock or severe

pulmonary injury in consultation with the pulmonary injury in consultation with the poison centerpoison center

Side effects: nausea/vomiting, headache, Side effects: nausea/vomiting, headache, burning sensation of lips, chest pain, anxietyburning sensation of lips, chest pain, anxiety

SummarySummary

Triage, decontamination, and isolation Triage, decontamination, and isolation preparredness are keypreparredness are key

Nuclear events present with blast and burn Nuclear events present with blast and burn injuries acutelyinjuries acutely

Aerosol dispersal is most likely for Aerosol dispersal is most likely for chemical and biological agents and will chemical and biological agents and will present with respiratory complaints present with respiratory complaints