Transcript Learning objectives

Cyanide Poisoning
Daniel Shodell MD, MPH
Anne Arundel County DOH, 2004
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Learning objectives
• Describe the clinical syndrome,
treatment, and epidemiology of cyanide
• Identify the key public health agency
response in a cyanide chemical terrorism
event
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Overview / Background
• Cyanide:
– recognized since antiquity
– present in bitter almonds, cassava, and other
foods
– used extensively in industry for fumigation,
electroplating, and mining activities
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Overview / Background
• Several forms exist; all may have an odor of
bitter almonds, but this is not always
detectable
– Gas: colorless, dissipates rapidly
• hydrogen cyanide [HCN] and cyanogen chloride
[CNCl, also known as CK]
– Liquid: ranges from blue to colorless, stable
• hydrocyanic acid; an aqueous solution of HCN
– Solid: white granular powder, stable
• sodium, potassium, or calcium
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Overview / Background
• Tylenol tampering in 1982
– 7 deaths
– subsequent events involved other over the counter
medications and prepared foods
• Easily available
– cheap
– plentiful supplies in industry
– large scale contamination (eg. municipal water
supplies) unlikely due to enormous quantity required to
achieve toxic levels in a large body of water.
– single or multiple local events are more likely
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Overview / Background
•
Current threat is both domestic and international
– 2003 search of a Texas property revealed cyanide salts
that were possibly intended for use in domestic militia
activities (1)
– international terrorist groups have also been found to
possess stores of cyanide (2, 3)
Sources
(1) ATF www.atf.gov/press/fy04press/field/051104dal_chemweapons.htm
(2) CNN edition.cnn.com/2003/US/02/06/sprj.irq.alqaeda.links/index.html
(3) CBWInfo www.cbwinfo.com/Chemical/Blood/AC.shtml
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Epidemiology
• Acute v. Chronic poisoning
– Varying clinical presentation
– This presentation will focus on acute
intoxication, consistent with a terrorist event or
industrial accident
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Epidemiolgy - Routes of exposure
• Gas: Inhalation
– hydrogen cyanide
– cyanogen chloride
• Liquid: Inhalation (aerosol), ingestion, skin
contact
– hydrocyanic acid
• Solid: Inhalation, ingestion, skin contact
– cyanide salts
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Clinical manifestations
• Mechanism:
– inhibits mitochondrial cytochrome oxidase
– an “asphyxiating” agent
• Primarily targets CNS and cardiac tissue,
but multiple systems involved
• Presentation depends on dose and route of
exposure
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Clinical manifestations
• Common final pathway for cyanide intoxication is
cellular hypoxia. Exposure to any form of
cyanide:
– Metabolic acidosis: nonspecific symptoms
– CNS: dizziness, nausea, vomiting, drowsiness, tetany,
trismus, hallucations
– CV: arrhythmia, hypotension. Tachycardia and
hypertension may occur transiently in early stages
– Respiratory: dyspnea, initial hyperventilation followed
by hypoventilation and pulmonary edema. Cyanosis
not apparent, since blood is adequately oxygenated
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Clinical manifestations
• Time to onset of symptoms, as well as additional
signs of exposure, depends on dose and route of
exposure:
– Inhalation
• Rapid onset: seconds to minutes
• Additional signs: Metallic taste; burning sensation in GI /
respiratory tract
– Ingestion
• Delayed onset: 15 to 30 minutes
• Additional signs: Sore throat; burning sensation in GI /
respiratory tract; diarrhea
– Skin contact
• Delayed onset: 15 to 30 minutes
• Additional signs: Erythema, pain at site of contact
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Diagnosis
Diagnosis is primarily made by index of suspicion and clinical judgement
• Case history
– suspicion of exposure
• Clinical presentation
– metabolic acidosis, multisystem involvement
– odor of bitter almonds
• Laboratory diagnosis
– blood cyanide levels can be drawn, but empiric treatment is
almost always required before lab results are available
– high anion gap metabolic acidosis
– arterial and venous pO2 may be elevated
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Treatment
• Treatment protocol differs between United
States and other industrialized nations
• Within the United States, new consensus is
developing regarding best practices
• Treatment regimen depends on severity of
symptoms, route of exposure (to some
extent), and what is available
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Treatment: overview
1)
2)
3)
4)
5)
6)
7)
Activated charcoal
Supplemental oxygen
Supportive care / ACLS
Sodium nitrite
Amyl nitrite
Sodium thiosulfate
Hydroxocobalamin
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Treatment
1) Activated charcoal
-For alert, asymptomatic patients following ingestion
2) Supplemental oxygen
-100% for suspected exposure
3) Supportive care / ACLS
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Treatment
4) Sodium nitrite
-Mechanism: forms methemoglobin, competes with cytochrome oxidase
for free cyanide; combines with cyanide to form
cyanmethemoglobin
-Dose: Adults: 300mg IV over 5 minutes; slower if hypotension
develops
Children: 0.12 to 0.33 mg/kg IV infused as above
-Adverse reactions: Hypotension associated with rapid infusion,
tachycardia, syncope, cyanosis due to methemoglobin formation,
headache, dizziness, nausea, vomiting. Frequency of events is not
clearly defined
5) Amyl nitrite
-An inhaled drug, similar to sodium nitrite but with little systemic
distribution: second line agent used when sodium nitrite is not
avaialable
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Treatment
6) Sodium thiosulfate
-Mechanism: sulfur donor promotes rhodanase activity:
detoxifies cyanide as it is released from
cyanmethemoglobin. Directly detoxifies cyanide by
conversion to thiocyanate; too slow to be useful as a firstline intervention
-Dose: Adults: 12.5g IV over 10-20 minutes following
administration of sodium nitrite
Children: 412.5mg per kg IV over 10-20 minutes
-Adverse reactions: Hypotension, CNS depression and coma
due to thiocyanate intoxication, psychosis, confusion,
weakness, tinnitus, contact dermatitis. Frequency of
events is not clearly defined
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Treatment
7) Hydroxocobalamin
-Mechanism: direct binding agent, chelates cyanide
-Dose: 4 to 5 g IV
-Adverse reactions: minimal toxicity
-Additional information:
-not the drug of choice in the United States, in part due to its high
cost; more common in Europe
-other chelating agents, such as dicobalt edetate, are not
generally used in the United States due to toxicity
-not yet approved by FDA
[Mokhlesi B, Leiken JB, Murray P, Corbridge TC. Adult toxicology in critical care: Part II: Specific
poisonings. Chest. 2003 Mar;123(3):897-922]
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Treatment
• Typical cyanide treatment kit in the United
States is stocked with:
– Amyl nitrite ampules
– Sodium nitrite solution
– Sodium thiosulfate solution
• Speed is critical for survival
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Clinical outcomes
• Without treatment:
– Lethal exposure levels will result in rapid death
• With supportive treatment and specific
antidotes:
– Lethal exposure levels can be survived with
immediate medical management
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Decontamination
• Gas:
– exposure does not require decontamination or contact
precaution
• Liquid or solid:
– treatment team is at risk for contact exposure or
inhalation of gas produced by significant quantities of
remaining cyanide compounds
– skin decontamination can be achieved using a rinse
with dilute detergent
– contaminated clothing should be removed,
preferentially by the patient if alert and asymptomatic,
and placed in sealed bags
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Differential Diagnosis
• Causes of anion gap metabolic acidosis:
– “CATMUDPILES”
•
•
•
•
•
•
•
•
•
•
•
CO, CN
Alcoholic ketoacidosis
Toluene
Methanol
Uremia
DKA
Paraldehyde
Iron, INH
Lactic acidosis
Ethylene glycol
Salicylates
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Public health response
• Reporting
– Critical for enabling surveillance: used to
establish baselines that are used for comparison
when analyzing a potential terrorist event
– Reporting is the first step in coping with a
covert chemical event
– County or state Department of Health
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Summary
• Cyanide intoxication diagnosis and treatment has
current bearing on clinical practice
– terrorism
– industrial accident
• The hallmark of cyanide is asphyxiation and
metabolic acidosis without cyanosis
• Effective treatment is available
• Both baseline and outbreak reporting are critical
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Resources
• Anne Arundel County physician link
• Essential Reading
– Cummings, TF. The treatment of cyanide poisoning. Occupational
Medicine. 2004; 54:82-85
• Additional Reading
– Centers for Disease Control and Prevention. Recognition of illnesses
associated with exposure to chemical agents – United States 2003.
Morbidity and Mortality Weekly Report. 2003: 52(39);938-940
– Centers for Disease Control and Prevention. Biological and chemical
terrorism: Strategic plan for preparedness and response. Morbidity and
Mortality Weekly Report. 2000; 49(RR-4):1-14
– Mokhlesi B, Leiken JB, Murray P, Corbridge TC. Adult toxicology in
critical care: Part II: Specific poisonings. Chest. 2003 Mar;123(3):897922
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Resources
• Web Resources
– Centers for Disease Control and Prevention, Emergency Preparedness and
Response www.bt.cdc.gov/agent/cyanide
– Health Protection Agency Guidelines for Action in the Event of a
Deliberate Release: Hydrogen Cyanide
http://www.hpa.org.uk/infections/topics_az/deliberate_release/chemicals/c
yanide.pdf
– The National Institute for Occupational Safety and Health, Online NIOSH
Pocket Guide to Chemical Hazards
http://www.cdc.gov/niosh/npg/npgd0000.html
– Agency for Toxic Substances and Disease Registry Public Health
Statement for Cyanide http://www.atsdr.cdc.gov/toxprofiles/phs8.html
– Agency for Toxic Substances and Disease Registry Medical Management
Guidelines for Hydrogen Cyanide
http://www.atsdr.cdc.gov/MHMI/mmg8.html
– CBWInfo Factsheets on Chemical and Biological Warfare Agents,
Hydrogen Cyanide http://www.cbwinfo.com/Chemical/Blood/AC.shtml
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