WEAPONS OF MASS DESTRUCTION

The Health Care Professional’s Role in

Preparation & Response

Course Objectives• At the conclusion of this program, participants will be able to:• Define the term weapons of mass destruction (WMD) and categorize the types of WMD most likely to be used in acts of terrorism;• Discuss how acts of terrorism involving WMD have impacted the public health system and the practice of medicine;• Recognize the signs and symptoms of exposures to WMD; Utilize current treatment modalities for patients exposed to WMD;• Explain the health care practitioner’s role in syndromic surveillance and reporting; and use the Health Alert Network as an informational resource.• Identify personal protective equipment needed by health care practitioners when treating patients exposed to WMD;• Explain the procedures necessary to decontaminate a casualty.

Weapons of Mass Destruction The Threat

U.S. Threat increasing: Accessibility to these materials by an increasing number of potential adversaries:

International instability

Terrorist networks

Strength and perceived invulnerability of the United States’ homeland and military.

Changing dynamics of non-state violence.

Weapons of Mass Destruction The Threat

Why Use WMD Agents?• Four dangerous characteristics• Lethality• Small quantities = devastating effects• Portability • Not easily detected• Accessibility• State sponsored terrorism• Black market sales• Easy to produce• Commercially available products

Consequences:• Potential for massive casualties• Panic• Fear of the unknown: In the Tokyo subway attack out of the 5,510

individuals seeking medical attention. 4,073 were not exposed.

• Contamination• Economic damage• Loss of strategic position• Social-psychological damage & political change

• Education For ourselves For our patients

• Recognition When an incident occurs What is the cause When to report

• Treatment Supportive care Pharmacotherapy Decontamination

Role of Healthcare Providers

Medical Aspects of

Nuclearand

Radiological Agents

Ionizing Radiation Basics

Alpha Particle• Heaviest and most highly charged• Least penetrating• Travel 4-7 inches in air• Stopped by an ordinary sheet of paper• External exposure not a serious hazard• Internal exposure can be the most damaging source of radiation exposure

Beta Particle• Smaller and travel much faster than alpha particles• Penetrate further into any material or tissue• Can travel several millimeters through tissue but generally not far enough to tissue, reach vital organs• May be a major hazard when internal

Gamma Ray• Similar to medical x-rays• Are a type of electromagnetic radiation• The most hazardous type of radiation from sources outside the body• Greatest distances and penetration

Penetrating Power

Ionizing Radiation Basics

• Hospital radiation therapy Cobalt-60, Cesium-137

• Nuclear power fuel rods Uranium-235. Plutonium

• Universities, laboratories, radiography and gauging Cobalt-60, Cesium-137, Iridium-192, Radium-226

Sources of Ionizing Radiation

Measurement• Rad (R): Traditional unit (Radiation Absorbed Dose)• Gray (Gy): Sl unit 1 Gy=100 rad=100 cGy (=1 J/Kg)• Rem (R): Traditional unit• Effective dose (Rad x weighting factor)• Sievert (Sv): Sl unit• 1 Sv=100 rem=100 cSv

Dose in Perspective (mrem)• Chest x-ray 20• US average/year 360• Occupational annual limit 5 000• Detectable physical effect 20,000• Physical symptoms 100,000• Death possible 250,000• LD50 450,000

Measurementand

Dose Perspective

of Ionizing

Radiation

Radiation Exposure

Nuclear• Nuclear threat unlikely• Expensive• Logistically intensive• Technologically difficult• Attacks against nuclear storage facilities, power plants or transportation systems possible

Radiation Dispersion Devices• RDD’s or “Dirty Bombs”• Combines conventional explosives with a radioactive source (ionizing radiation)• First seen in 1995 (Chechen rebels) • Not a “fission” or “fusion” process• Tool of fear• Most probable sources would not cause severe illness from radiation• May prevent the use of an area for prolonged periods

• Radiation interacts with atoms, depositing energy and resulting in ionization

• Ionization can damage critical molecules or structures in a cell

• Directly hits a particularly sensitive atom or molecule in the cell

• Irreparable; the cell either dies or malfunctions

• Indirectly by interacting with water molecules

• Deposited energy leads to the creation of unstable, toxic hyperoxide molecules

Clinical Effects

Acute Radiation SicknessA combination of clinical syndromes occurring:

In stages (prodromal, latent, manifest illness)

During a period of hours to weeks after exposure, as injury to various tissues and organs isexpressed.

Hematopoietic Syndrome• Dose range: > 0.7 Gy• Effects: stem cells of all marrow cell lines• Prodromal Period Nausea, vomiting, anorexia, possible diarrhea Onset at 3-24 hours, duration <48 hours Severity = increases with dose• Latent Period Mostly asymptomatic, except mild weakness 3-4 weeks Hair loss/weight loss, about day 14 Manifest Illness Onset 3-5 weeks Bone marrow atrophy hemorrhage and infection

Clinical Effects

Gastrointestinal Syndrome• Dose range: >6 Gy• Effects: Gl stem cells and small vessels Prodromal Period Severe N/V diarrhea fever in 1-4 hours• Latent Period 5 – 7 days Manifest Illness Paralytic ileus, bloody diarrhea, severe vomiting, shock, sepsis

Cardiovascular / CNS Syndrome• Dose: >20 Gy• Effects: small blood vessels, especially in brain• Cerebral edema, death 2-3 days

Clinical Effects

Triage• By conventional injuries• Trauma• Burns• By radiation injury• Prodromal symptoms• N/V < / > 4 hours is the yardstick• Hematologic picture

Treatment• Standard emergency medical procedures• Decontaminate AFTER stabilized• Radiation injury NOT acutely life threatening• Supportive Care • Clean environment• Vascular integrity: IV fluids, blood products, stop losses• Prophylactic antibiotics• Definitive Treatments• Cytokines

Clinical Actions

Internal Contamination• Reduce intake and deposition• Increase elimination• Blocking and Diluting Agents• Kl, calcium, aluminum, barium, strontium salts• Chelating Agents• EDTA, DTPA, Deferoxamine, Penicillamine, Prussian Blue

Dosimetry• Initially• RADIACs• Nasal swabs (~5% of lung deposition)• Skin appearance• CBC q 4-6 h• Later• Nuclear medicine equipment• Bioassay: Excretion Sampling• Baseline and 24-hour urine/stool collections (according to nuclide)

Clinical Actions

Medical Aspects of

Chemical Agents

Chemical Agent Hazards• The ability to present a health hazard is dependent upon:• The composition of the material• Volatility or persistency• Route of exposure• Amount of exposure

Composition• Aerosol – a collection of very small solid particles or liquid droplets suspended in a gas• Vapor – the gaseous form of a substance at a temperature lower than the boiling point of that substance at a given pressure

Key Point: Aerosols settle faster than vapors

Medical Aspects

Volatility / Persistency

Volatility – the degree to which asubstance will spontaneously evaporate• Dependent upon:• Chemical composition• Ambient temperature and air pressure• Wind speed• Surface contact

Persistency – the degree to which asubstance resists evaporation and poses aliquid hazard.

Key Point: Volatile chemicals are a vapor hazard Persistent chemicals are a contact hazard.

Route to Exposure• Persistent agents exert toxic effects primarily by direct exposure• Systemic absorption may occur with large exposures• Non-persistent agents are primarily a respiratory hazard• Vapor may effect the eyes and skin

Amount of Exposure• Effects are proportional to the amount of exposure• For liquid exposure:• ED50 is the amount of agent that will cause effects in 50% of those exposed• LD50 is the amount that will result in death in 50% of those exposed

For vapor exposure:• Concentration time product (Ct) is used• Calculated based on agent concentration 62g and duration of exposure• Concentration expressed as mg/m³• Time expressed in minutes• Does not take into account rate and depth of respiration

ExampleExposure to 4 mg/m³ of a given agent for 10 minutes = Ct of 40-mg m/m3

Exposure to 10 mg/m³ of a given agent for 4 minutes = Ct of 40-mg m/m3

Classification & Characteristics

Nerve Vesicarts CyanideBlood Pulmonary Riot Control

Tabun

Sarin

Soman

Mustard

Lewisite

Phosgene Oxima

Hydrogen Cyanide

Cyanogen Chloride

Phosegene

Chlorine

Maze

Tear Gas

Pepper Spray

Generally liquid at room temperature• Disseminated as vapor or aerosols• Time of onset is seconds to hours

VX

Nerve Agents

AGENT Tabun Sarin Soman VX

AGENT SYMBOL

GA GB GD VX

ODOR None or fruity

None or fruity None None or Sulfur

RATE OF ACTION

INHALATION: Very fast

Skin penetration: seconds to minutes

PERSISTENCY Non-persistent Persistent

Mechanism of Action• A substance that causes effects by inhibiting acetylcholinesterase ( AChE)• The enzyme that breaks down acetylcholine (Ach)

Normal Physiology

Electrical impulse goes down nerve

Impulse causes release of ACh, carrying impulse across synapse

ACh Stimulates receptor site on organ & causes organ to act

ACh is destroyed by AChE

Organ activity ceases

Nerve Agents

Exposure to Nerve Agent

Impaired Physiology

AChE is inhibited and does not destroy Ach, which continues to stimulate organ and causes overstimulation

ToxicityLCt LDmg-min/m³ mg/70kg

GA 400 1,000GB 100 1,700GD 70 50VX 10 10

Nerve Agent Clinical Effects

Effects of exposure depend on dose and route• Small amounts of vapor first affect sensitive organs of the face, eye, airway• Small amounts of liquid on the skin causes localized affects at the

point of contact• Lethal amounts cause rapid cascade of events

Eye• Miosis is a characteristic sign of exposure• Complaints of Pain Dim vision Blurred vision Conjunctival injection

Respiratory• Rhinorrhea (dose dependent)• Bronchoconstriction and increased

secretions• Respiratory arrest (CNS mediated)• Complaints of• Tight chest• Severe breathing difficulty• Gasping, irregular breathing

Gastrointestinal / Genitourinary• Nausea, vomiting• Pain in abdomen•Diarrhea involuntary defecation or urination

Glands• Increase in secretions Lacrimal Nasal Salivary Bronchial

Skeletal Muscle• Fasciculation and twitching• Large amount• Fatigue• Muscular flaccidly

Central Nervous System• Large amounts• Loss of consciousness• Seizure activity• Apnea• Begins in minutes after large exposure• Asymptomatic period of 1 to 30 minutes

after skin contact with a liquid agent

SLUDGES - SalivationL - LacrimationU - UrinationD - DefecationG - Gastric distressE - Emesis

Nerve Agent Clinical Effects

Laboratory Findings• Decreased RBC-ChE activity• Poor correlation between degree of enzyme inhibition and amount of

exposure or physical signs • Severe systemic effects generally indicate inhibition of 70 – 80%• Wide inter- and intrapersonal variability• Other laboratory findings will relate to complications

Medical ManagementManagement of a casualty with nerve agent intoxication consists of decontamination, ventilation, administration of antidotes, and supportive therapy. The condition of the patient dictates the need for each of these and the order in which they are instituted.

Ventilation• Requirement may last from 0.5 to 3 hours• Airway resistance is high (50-70cm of water)• Bronchoconstriction and secretions require vigorous pulmonary toilet

Antidotes• Atropine• Pralidoxime chloride•Benzodiazepenes

Atropine• Anticholinergic drug• Blocks excess acetylcholine• Clinical effects at muscarinic sites• Dries secretions & relaxes smooth muscle• Dose• 2mg every 15 minutes• Can require 15 to 20 mg• Therapy endpoints• Atropine eyedrops

Pralidoxime Chloride• Attaches to the nerve agent and breaksthe agent-enzyme bond• Clinical effects at nicotinic sites • Stops muscle fasiculations• Dose• Should be initiated concurrently with atropine• 1 gram IV over 20min• Repeated q1h for two or three additional doses

Benzodiazepenes• Diazepam / Lorazapem• Decrease seizure activity• Administered to patient with severe symptoms regardless if seizure activity is present• Further doses titrated to seizure activity

Nerve Agent Actions

Triage Immediate • Unconscious • Convulsing • Postictal • Apneic

Minimal• Walking and talking after exposure

Delayed

• Liquid – contamination without symptoms

• Recovering after antidotal therapy

Nerve Agent Actions

Vesicants

AGENT Mustard Lewisite Phosgen Oxime

AGENT SYMBOL H K CX

ODOR Garlic Geraniums Irritating

RATE OF ACTION

No immediate symptoms absorption in seconds

Immediate Pain Immediate symptoms can get worse every time

PERSISTENCY Persistent Persistent Non-persistent

Mechanism of Action

• Cause of death by interfering with DNA and cellular function (radiomimetic)

• Primarily a liquid threat may become vapor at higher temperatures

• Agents– Mustard (H, HD)– Lewisite (L)

Toxicity

• Through skin surfaces within 2 minutes– Cellular interaction: 1 to 2 minutes– Clinical effects: 2 to 48 hours (avg. 4-8)

• Penetration is enhanced by moisture, heat, and thin skin

Liquid• Blister 10μg• Death 100 mg/kg 7 gm/70 kg

Clinical Effects of Nerve Agents

• Have local and systemic effects

• Effects dependent on:– Ambient temperature and humidity– Site exposed

Skin

• Erythema (appears 2 – 48hrs)

• Small vesicles; later coalesce

• Blisters (12 – 24hrs)

• Blister fluid is clear, and does not contain mustard

• Weeks to months for complete healing

Clinical Effects of Nerve Agents

Airway

• Upper Airway– Burning & irritation of nose, sinuses & pharynx;

laryngitis and nonproductive cough– Damage to the trachea and upper bronchi lead to

productive cough• Lower Airway

– Increasingly severe productive cough– Distal airways & alveoli only affected in terminal

event: pulmonary edema not usually seen• Death by respiratory failure

– Mechanical obstruction & laryngospasm– Secondary pneumonia

Clinical Effects of Nerve Agents

Eye

• Very sensitive to mustard vapor• Short latent period• Mild

– Conjunctivitis– Blepharospasm

• Moderate– Lid inflammation, edema

• Severe– Corneal opacification, ulceration, perforation

Clinical Effects of Nerve Agents

GI

• Primarily through ingestion

• Early (<24 hours)– Transient symptoms– Cholinergic effect

• Late (>3 days)– Severe damage– Cytotoxic effect

Clinical Effects of Nerve Agents

CNS

• CNS effects remain poorly defined

• Animal work demonstrates mustards are convulsants

• Several human case reports describe neurological effects with large amounts

Clinical Effects of Nerve Agents

Hematopoetic

• Bone marrow depression– Severe cases of skin and inhalation exposure– Usually irreversible

Clinical Effects of Nerve Agents

Diagnostic Studies

• Differential diagnosis includes contact dermatitis, drug eruption, or severe sunburn

• CBC

- Early leukocytosis followed by leukopenia

• Early chemical pneumonitis– Fever, WBC, chest x- ray

• Pneumonia: sputum exam / culture

Medical Management: Skin

• Soothing cream/lotion (0.25% camphor and menthol, calamine)

• Small blisters (under 1-2cm) left intact

• Systemic analgesics

• Appropriate IV fluids and electrolytes

Medical Management: Eyes

• Irrigation• Artificial tears• Topical mydriatics• Topical antibiotics• Vaseline on lid edges• Topical analgesics (nsaid drops)• Avoid topical anesthetics• Sunglasses

Medical Management: Airway

• Steam, cough suppressants• Oxygen• Bronchodilators, steroids• Early intubation• Assisted ventilation, early use of PEEP or

CPAP• Bronchoscopy• Antibiotics AFTER organism identified

Medical Management: GI

• Antiemetics

• Fluid therapy

• Electrolyte replacement

Antidotes

• British Anti-lewisite (BAL)– Initial dose: 0.5cc per 25 lbs IM (up to 4cc)– May be repeated at 4, 8, 12 hours after initial

dose

• Must consider toxicity of treatment– Hypertension– Nausea/vomiting

Triage

• Immediate Delayed• Airway effects • Most patients• within the first • 5% to 50% BSA

several hours after • Moderate lung

exposure effects

• Ocular injuries• Minimal

– Skin lesions covering <5% BSA

Cyanides / Blood Agents

AGENT Hydrogen Cyanide Cyanogen chloride

AGENT SYMBOL CX CK

ODOR Bitter almonds

RATE OF ACTION Immediate, Seconds

PERSISTENCY Non-persistent

Cyanides / Blood Agents

• Route of exposure is inhalation• Body can detoxify a limited amount

– Binds to sulfur molecule, converting to thiocyanate

• Primary site of action at cellular level• Interruption of cellular respiration in

mitochondria by binding to cytochrome a3– Result is anaerobic metabolism lactic to

acidosis

Clinical Effects

• Lower concentrations– Hyperpnea– Feelings of anxiety apprehension– Weakness– Nausea– Muscular trembling

• The “classical” cherry red skin, and smell of bitter almonds are seldom seen

Clinical Effects

• Higher concentrations

• Effects manifest primarily in the CNS

• Transient hyperpnea followed by convulsions ~ 15 seconds after exposure

• Respiratory activity ceases 2 – 3 minutes

• Cardiac activity ceases within 6 – 8 minutes

Diagnostic Studies

• Blood cyanide levels• Mild effects at 0.5 mcg/ml – 1.0 mcg/ml• Coma, convulsions and death at greater

than 2.5 mcg/ml• Anion gap acidosis• Venous blood gas analysis

• Higher than normal venous oxygen content

Medical Management

• General supportive therapy

• Ventilatory support

• Circulatory support (crystalloids/vasopressors)

• Treat metabolic acidosis (hyperventilation and bicardbonate administration)

• Specific antidotal therapy

• Cleaves cyanide-cytochrome a3 bond

• Sulfur donor

Antidotal Therapy

• Amyl nitrite• Given by inhalation by crushing vials

• 15 minutes on; 15 minutes off• Converts Hb02 (Fe2+) to metHb (Fe3+), but inhalation

leads to variable metHb levels • Sodium nitrite

• Converts Hb02 (Fe2+) to metHb (Fe3+)• 300 mg IV of a 3% soln (30 mg/mL) = 10

mL• Sodium thiosulfate

• Sulfur donor• 12.5 g IV of a 25% soln (250 mg/mL) = 50mL

Experience with Antidotes

“The combination of sodium nitrite and sodium thiosulfate is the best therapy against cyanide and hydrocyanic acid poisoning. The twosubstances intravenously injected, one after the other, namely the nitrite followed by the thiosulfate, are capable of detoxifying approximately twenty lethal doses of sodium cyanide in dogs and are effective even afterrespiration has stopped. As long as the heart is still beating, the chances of recovery by utilizing this method are very good.”-Chen et al.

Pulmonary Agents

AGENT Phosgene Chlorine

AGENT SYMBOL CG CL

ODOR Newly mown grass or hay

Swimming pool

RATE OF ACTION Immediate symptoms can get worse over time

PERSISTENCY Non-persistent

Triage

• Immediate Delayed• Presents within • Mild effects

minutes with • Successfullyapnea or seizure treated

Minimal• Asymptomatic 5 minutes after removal

from exposure

Toxicity

• Absorbed almost exclusively by inhalation

• Penetrates down to bronchioles & alveoli

• Consumed at the alveolar capillary alveolar-membrane– No significant systemic distribution

• Membrane injury results in fluid extravasation and pulmonary edema

Clinical Effects

• Pulmonary symptoms develop following a latent period that is dependent on dose and physical activity post-exposure

• Airway Eye• Mild cough • Ocular irritation

• Dyspnea • Lacrimation• Chest tightness • Corneal• Rales opacities• Laryngospasm • Corneal

perforation

Diagnostic Studies

• Differential Diagnosis• Other chemical agent exposures• Other causes of pulmonary edema

• No commonly available laboratory tests• Increased hematocrit may reflect hemoconcentration• Arterial blood gases may show a low PaO2• Decreased peak expiratory flow rates• Early findings on chest x-ray are hyperinflation,

followed by pulmonary edema

Medical Management

• Supportive care• Strict bed rest• O2, PPV with PEEP / CPAP to maintain

PaO2• Bronchodilators for bronchospasm• IV fluids for hypotension (3rd spacing)• Surveillance cultures• Antibiotics when indicated

Triage

Immediate Delayed• Pulmonary edema • Dyspnea with no

anytime after objective findings exposure • Re-triage q1h

• Observe 24hMinimal

• Asymptomatic with known exposure• Mild eye or upper airway irritation• Re-triage q2h, Discharge in 12h

Summary

Weapons of Mass Destruction can include:

• Nuclear and Radiologic Agents

• Chemical Agents

• Nerve Agents

• Pulmonary Agents

Triage and Treatments

• Vary by type of agent and exposure