Clinical toxicology

class no. 6
 Overview / Background
 Cyanide:
 recognized since antiquity
 present in bitter almonds, cassava, and other foods

 used extensively in industry for fumigation,

electroplating, and mining activities
 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
 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 [Link]/press/fy04press/field/051104dal_chemweapons.htm
(2) CNN [Link]/2003/US/02/06/[Link]/[Link]
(3) CBWInfo [Link]/Chemical/Blood/[Link]
 Epidemiology
 Acute v. Chronic poisoning
 Varying clinical presentation
 This presentation will focus on acute intoxication,
consistent with a terrorist event or industrial
accident
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
 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
 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
 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
 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
 Treatment

 Treatment regimen depends on severity of

symptoms, route of exposure (to some
extent), and what is available
 Treatment: overview
1) Activated charcoal
2) Supplemental oxygen
3) Supportive care / ACLS
4) Sodium nitrite
5) Amyl nitrite
6) Sodium thiosulfate
7) Hydroxocobalamin
 Treatment
1) Activated charcoal
-For alert, asymptomatic patients following ingestion
2) Supplemental oxygen
-100% for suspected exposure
3) Supportive care / ACLS
 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
 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 first-
line 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
 Treatment
7) Hydroxocobalamin
-Mechanism: direct binding agent, chelates cyanide
-Dose: 4 to 5 g IV
-Adverse reactions: minimal toxicity
 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

 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
 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
 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
 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
 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
Iron poisoning