Download Managing Chemical & Radiological Exposure

Managing Chemical
Exposure
Kevin O. Rynn, PharmD, FCCP, DABAT
Clinical Associate Professor
Clinical Pharmacy Specialist Emergency
Medicine
Awakening of America
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Objectives:
Identify agents potentially used in a terrorist
attack
Understand the pharmacology and toxicology
of these agents
Understand the management of exposed
patients
Identify unique potential threats to New
Jersey residents
Better appreciate our role as pharmacists
Introduction: Chemical
Warfare
Spartans, 429 BC
World War I: Germany
 April 22nd 1915: chlorine gas against allies

Belgium, Hundreds killed, troops retreated
 July 12th, 1917: Sulfur mustard

Injuries >>> fatalities
World War II: Germany
 December 2nd 1943: Mustard bombs destroyed in Italy
Yemen war
 Egypt: riot control agents, mustards, nerve agents
Vietnam
 US: Tear gas and chemical herbicides
Introduction: Chemical
Terrorism
Aum Shinrikyo Cult
Introduction: Chemical
Terrorism
Matsumoto: 1994
 Sarin: residential neighborhood
 Fatalities: 7
 Hospital visits: 500
Tokyo: 1995
 Sarin, subway system during
rush hour
 Fatalities: 12
 Hospital visits: > 5,000
Subway riders injured in Aum Shinrikyo
sarin gas attack, Tokyo, March 20, 1995.
(AP Photo/Chikumo Chiaki )
Signs & Symptoms of 111 Moderately or
Severely Injured Patients on Admission
Eye





GI
Miosis 99%
Eye pain 45%
Blurred vision 40%
Dim vision 38%
Tearing 9 %
Chest







Dyspnea 63%
Cough 34%
Wheezing 6%
Tachypnea 32%






Runny nose 25%
Sneezing 9%
Nausea 60%
Vomiting 37%
Diarrhea 5%
Neurologic

ENT


Headache 75%
Weakness 37%
Fasciculations 23%
Numbness 19%
Decreased LOC 17%
Vertigo/dizziness 8%
Seizures 3%
Psychologic

Agitation 33%
Okumura T, et al Ann Emerg Med 1996;28(2):129-35
Chemical Weapons
Agent
Common Name
Code
Nerve
Agents
Tabun
Sarin
Soman
VX
Mustard
Lewisite
Phosgene oxime
Bis-2-chloroethylsulfide
GA
GB
GD
VX
HD
L
CX
T
Vesicants
Chemical Weapons
Agent
Common Name
Code
Blood Agents Hydrogen cyanide
Cyanogen chloride
AC
CK
Pulmonary
Agents
Phosgene
Chlorine
CG
CL
Riot Control
Agents
Mace
CR,CS,
CN,CA
Nerve Agents
Physical characteristics and toxicity
Mechanism:

Cholinesterase inhibitors, excess buildup of Acetycholine
(Ach)
Muscarinic effects

Postganglionic parasympathic
Nicotinic effects

Autonomic ganglia
 Preganglionic sympathetic & parasympathetic

Neuromuscular junction
Excess Ach in CNS
Results of
Cholinesterase Inhibition
Muscarinic
Diarrhea
Urination
Miosis**
Bradycardia
Bronchorrhea
Bronchospasm
Emesis
Lacrimation
Salivation
Lacrimation
Urination
Defecation
GI symptoms
Emesis
** Most important after nerve agent
Nicotinic
Tachycardia
Hypertension
Mydriasis
Neuromuscular junction**
Fasciculation
Weakness
paralysis
CNS
Anxiety, confusion, ataxia, dysarthria
Coma, Seizures**, Resp depression**
Key Findings Based
on Route of Exposure
Route &
Onset
Mild
Vapor/aeroso Rhinorrhea,
l
secretions,
slight dyspnea
Immediate
Topical
Immediate or
delayed
Localized
sweating &
fasciculations
Moderate
Severe
Miosis, eye pain,
dim vision,
pronounced
dyspnea
Coma,
convulsions,
fasciculations,
paralysis
Vomiting,
diarrhea,
secretions
Miosis, coma,
convulsions,
generalized
fasciculations
RBC & Plasma Cholinesterase
Levels
Clinical utility limited



Related to clinical effect, but not
consistently
Normal value range
Workplace usage
Do not wait on these for treatment!
Cholinesterase Levels
RBC




Difficult assay
inhibited preferentially
by VX and sarin
2-PAM: regenerates
levels
Regeneration rate: 1%
per day (erythrocyte
production)
Plasma


Easier assay
An acute phase
reactant (liver
protein)
 Affected by low
protein conditions

Declines faster
acutely and
regenerates faster
Treatment: Decontamination
Selective protective
measures

Lipophyllic agents can
penetrate latex and vinyl
 Nitrile, neoprene, butyl
rubber gloves


Leather
Shared Breathing air
Irrigation



Water
Hypochlorite solution
Alkaline soap
Atropine
Competitive MUSCARINIC antagonist
Peripheral > central
Mod. to Severe
 Blood brain barrier
2-3 times this
Dosing- IV or IM


Initial
Adult 2mg
Peds 0.02mg/kg (min 0.1mg)
Repeat Every 2 - 5 minutes
Endpoints

Reversal of muscarinic signs of toxicity
Atropine
Dosing in comparison to organic phosphorus
insecticide.
Tokyo subway sarin attack (N=111)
Doses > 2mg
18.9%
 Max dose administered
9 mg
Okumura T. et al Ann Emerg Med 1996;28(2):129-35

Adverse effects

Dry mouth&skin, mydriasis, paralysis of
accommodation, tachycardia
Atropine: Alternative Routes
and Supply Sources
Aerosolized
Ophthalmic


Miosis reversal
Causes photophobia
and loss of
accommodation
Glycopyrolate
IV administration of




EMS sources
Opthtalmic
Veterinary
Powder preparation
Rapid Atropine Reformulation
From Bulk Powder
Geller RJ, Lopez G, Cutler
S, Lin D, Bachman GF,
Gorman SE. Ann Emerg
Med 2003;41:453-6.


110 6mg syringes ~ 60
minutes
8 week testing
Kozak RJ, Siegel S, Kuzma J.
Ann Emerg Med
2003;41:685-8.


 USP standards + 5%
 5˚C: USP standards + 5%
 Pyrogen free

4 week testing
 Room Temp: USP standards
+ 5%
100 6mg syringes ~ 30
minutes
3 week testing
 microbiologic sterility testing

Cost Advantage
 $11 vs $5,000
®
Pralidoxime:Protopam
(2-PAM)
Cholinesterase reactivator
Dosing: IM or IV



Adult: 1-2 gms over 15-20 minutes then q6h for
24 hrs
Peds: 25mg/kg to max 1gm
C.I.: Adult 500mg/hr, peds 25mg/kg/hr
Improves all cholinergic symptoms
Aging


Covalent bond between nerve agent and enzyme
Irreversible dealkylation
Nerve Agent Aging:
Nerve Agent
GA (Tabun)
Aging t1/2
in Humans
> 14 hrs
GB (Sarin)
3 - 5 hrs
GD (Soman)
2 - 6 min
VX
48 hrs
Treatment: Continued
Mark 1 Kits
CANA


Convulsion antidote for nerve agents
Diazepam
NAPS


Nerve agent pre-treatment tablets
Pyridostigmine
Nerve Agent Antidote Program
ChemPack
Vesicants
Common Name
Sulfur mustard
Lewisite
Code
H, HD
L
Phosgene oxime
CX
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Vesicant Agents: Symptoms
Mild
Moderate
Severe
Onset
4-24 hrs
2-6hrs
1-2 hrs
Ocular
Tearing, itching
burning
Reddening,
swelling,
pain
Marked swelling,
cornea damage,
severe pain
Airway
Hoarseness, hacking
cough, runny nose,
sneezing, nosebleeds
Worsening
symptoms
Severe productive
cough, SOB
Skin
Erythema, blistering
Worsening
symptoms
Worsening
symptoms
Treatment
Decontamination


Water, hypochlorite
solutions
Avoid scrubbing and
hot water
Topical


Calamine/other
soothing lotions
Antibiotics
Systemic analgesia
Ocular injures





Irrigation
Mydriatics: homatropine
or other anticholinergics
Anesthetics
Ophthalmic ointments
Constant reassurance
Respiratory




Antitussives:
Bronchodilators/mucolytics
Antibiotics
Intubation
Treatment: BAL
British Anti-Lewisite: Dimercaprol



Metal chelating agent
BAL combined with lewisite forms stable 5
member ring
Dosing
 3 -5 mg q4hr x 4 doses

Adverse effects
 GI, Hypertension, tachycardia
 Peanut allergy
Blood Agents: Cyanides
Antiquated term

Carried via blood to exert it’s effect
French

Franco-Prussian war: Napoleon III first to use
WWI: French and British

Hydrogen cyanide and cyanogen chloride used on
battlefields
WWII:

German genocidal agent
Iran-Iraq war and Iraq’s suppression of Kurds

Apparent use with mass casualties reported
Cyanide: Tampering
1982: Chicago Tylenol

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7 deaths
1988: Yogurt
1989: Dept of Agriculture

Cyanide traces on fruit from Chile, possible
terrorist threat
Cyanide
Routes

Inhalation, ingestion, topical
Primary site of action

Cells rather than blood
Interruption of cellular respiration in
mitochondria
Cyanide: Mechanism of Toxicity
Binding of CN- to cytochrome a3 in
mitochondria


Stable but not irreversible
CN- has higher affinity for the Fe3+ in
methemoglobin
Interruption of oxidative phosphorylation

Decreased aerobic energy production(ATP)
Final results: cellular hypoxia
Cyanide Vapor Exposure
Moderate
Severe Exposure
Increased rate
and depth of
breathing
Dizziness, N/V,
HA
< 1min: Transient increased breathing
30 sec: Seizures
2-4 min: Cessation of respiration
4-8 min: Cessation of heartbeat
Cyanide
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Homicidal and suicidal use
Judicial execution
Combustion of plastics, cigarettes, vehicle
exhaust
Household products

Silver polish, acetonitriles
Industry: chemical syntheses
Hospital

Sodium nitroprusside
Cyanide Toxicity: Treatment
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Cyanide: Treatment
Healthcare worker protection
Supportive therapy
Antidotal therapy
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
Displace CN- from cytochrome A3
 Nitrite therapy

Enzymatic conversion of CN- to thiocyanate
 Thiosulfate therapy
Sodium Nitrite
Converts Hb(Fe2+ ) to MetHb (Fe3+)
Preferential binding of CNGoal MetHb = 20 - 30%
Adverse effects


Excessive methemoglobin production
Vasodilatation: hypotension
Sodium Thiosulfate
Enzymatic (rhodanese) reaction with CN
Formation of thiocyanate (SCN-)
Irreversible reaction
Renal elimination
Adverse effects - minimal


N/V
Arthralgias
Dosing
Adult
Na Nitrite
3%
Na Thiosulfate
25%
Pediatric
300mg
10mg/kg (0.33 ml/kg)
(10ml) IVP (Dose adjusted in
anemic patients)
12.5 gms 412 mg/kg (1.65
(50 ml)
ml/kg)
IVP
Pulmonary Agents: Chlorine
and Phosgene
Increased permeability

Delayed pulmonary edema
WWI: Primary chemical agents
Chlorine: yellow-green cloud, pungent
Phosgene: colorless, fresh hay
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Pulmonary Agents
Mild Symptoms
Phosgene
and
Chlorine
Moderate to Severe
Symptoms
Nose and throat Laryngitis, wheezing,
irritation, cough, stridor, laryngeal
chest tightness edema, Acute lung
injury
Pulmonary agents- Phosgene
Low-solubility = deeper lung penetration
Symptoms within 4 hrs


Worse prognosis
ICU admission
No chest x-ray changes within 8 hours

Acute lung injury unlikely
Delayed serious symptoms

15 -18 hours
Pulmonary Agents: Treatment
Decontamination
Irrigation of eyes and skin
Oxygen
Endotracheal Intubation

Hoarseness, stridor, upper-airway burns,
wheezing, altered mental status
Bronchodilators
Nebulized sodium bicarbonate

Neutralize chlorine derivatives
 Efficacy data lacking
Pulmonary Agents: Treatment
Bed rest

Physical exertion exacerbates lung
inflammation
Corticosteroids

Moderate to severe exposures
Positive End Expiratory Pressure (PEEP)
Antibiotic prophylactic use

Not recommended
Riot Control Agents
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Tear gas or lacrimators
Aerosolized solids
Intense immediate self-limiting
symptoms
Prolonged exposure with underlying
lung disease

Bronchospasm and acute lung injury
Riot Control Agents
Chloroacetophenone - CN
o-chlorobenzilidene malononitrile - CS
Symptoms



Lacrimation, photophobia, blepharospasm
Chest tightness, wheezing, coughing, secretions
Dermal burning, erythema, vesiculation
Recovery: 15 - 30 minutes post removal
Riot Control Agents: Treatment
Removal from exposure
Remove clothing and placed in airtight bags
Irrigation
Symptomatic treatment

Ophthalmic anesthetics, bronchodilators,
antihistamines
Capsaicin-induced dermatitis

Oil immersion
Prevalent New Jersey HazMat
Threats
Terrorist attack likely to involve conventional
explosives & hazardous materials
New Jersey likely target


Densely populated state
Many companies/manufacturers
Most New Jerseyans live/work
within short distances to
chemical plants
Marcus, S, Ruck B. New Jersey Medicine 2004;101(9):34-43.
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New Jersey Department of
Environmental Protection (DEP)
New Jersey Toxic Catastrophe
Prevention Act (TCPE)


> 100 companies
Implement risk management plan (RMPs)
NJ DEP list chemicals and threshold
quantities
http://www.nj.gov/dep/rpp/tcpa/
New Jersey’s Top 10 List
Ammonia
Chlorine
Difluoroethane
Hydrogen chloride
Hydrogen fluoride
Hydrogen sulfide
Ozone
Pentane
Toluene diisocyanate
Vinyl Acetate
monomer
Ammonia
Background

Refrigerant, fertilizer, explosives, synthetic fiber,
petroleum industry, manufacture of chemicals
including methamphetamine
Signs and Symptoms

Ocular and respiratory
Treatment


Supportive
Copious amounts of water
Chlorine
Background


Bleaching fabrics, rubber and plastic
manufacturing, production of chemicals, meds,
and pesticides, water purification, sanitizing
Reacts with water to form HCl and hypochlorous
acid
Signs & Symptoms

Ocular and respiratory
Treatment


Supportive
Cautious supplemental O2
Hydrogen Fluoride
Background






Electronic circuits and plastics production
Glass, metal, stone, porcelain etching
Cleaning products
Fluoride ion responsible for tissue damage
Readily penetrates and causes deep tissue
destruction/burns
Hypocalcemia
Signs & Symptoms


Derm: Burns, erythemia, pain
GI: N/V abdominal pain
Hydrogen Fluoride: Treatment
Assess electrolyte and cardiac status
Irrigation
Calcium gluconate




Forms insoluble precipitate of calcium
fluoride, preventing absorption of F ion
Alleviate pain and prevent extension
Topical, intra-dermal, intra-arterial
Inhalation
New Jersey Conclusions
Many Locations that house chemicals

Risks to citizens working in or living near
Health care works prepare to manage
these exposures
Protocols should be available
Conclusions
Hospital roles
Pharmacist roles
Poison center roles
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