AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Cyanogen chloride (North Atlantic Treaty Organization [NATO] designation CK) is one of two volatile cyanide military chemical warfare agents. The other similar agent is hydrogen cyanide, or AC (please see CBRNE - Cyanides, Hydrogen). These agents first were used in large quantities by the French and British during World War I. While the United States maintained 500-pound and 1000-pound CK bombs, these were not used during World War II. More recently, Iraq is suspected to have used a cyanide-like agent against the Kurds in the 1980s.

Although CK and AC are similar in their toxicity, a few important differences exist. Firstly, CK is less volatile than AC, making it more effective at low concentrations. Secondly, by nature of its chlorine moiety, CK causes irritation of the eyes and respiratory tract and potential delayed pulmonary toxicity similar to chlorine or phosgene gases. In high concentrations (eg, in enclosed spaces), CK is a rapidly acting lethal agent, causing death within 6-8 minutes if inhaled at doses at or above its LCt50 (lethal concentration that kills 50% of people; 11,000 mg·min/m³).

CK is synthesized in the United States for industry by Matheson Tri-Gas and is used as an organic precursor and in mining and metalworking. Therefore, an emergency physician may be more likely to encounter CK-exposed victims following an industrial accident rather than in a warfare or terrorism scenario.

Pathophysiology

In addition to CK's local irritant effects, systemic toxicity occurs through mechanisms similar to those seen with hydrogen cyanide exposure (see CBRNE - Cyanides, Hydrogen). CK liberates a cyanide molecule, which enters the blood stream and distributes to tissues. Once inside cells, CK binds to mitochondrial cytochrome aa3, interrupts electron transport, and creates imbalance between ATP synthesis and hydrolysis. Oxygen is unable to be used effectively as the terminal electron acceptor, which forces a shift to anaerobic metabolism. While all organ systems are impacted, the most oxygen-dependent ones are the most affected (ie, brain, heart).

Frequency

United States

The major source of cyanide poisoning in the United States does not come from CK but rather from smoke inhalation during house and/or industrial fires in which plastics (acrylonitriles, polyurethanes), wool, or silk are burned. Cyanide poisoning also is found in association with chemical synthesis, electroplating, mineral extraction, dyeing, photography, and agriculture.

Mortality/Morbidity

In high concentrations, which can be obtained in enclosed spaces, CK is a rapidly acting lethal agent causing death within 6-8 minutes.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

When taking a history from a patient with possible toxic gas exposure, ask about the smell and color of the gas, onset of symptoms, duration and severity of symptoms, and effect on surroundings (eg, dead animals, other people). CK is a colorless liquid or gas with a pungent biting odor, which may in fact go unnoticed because of discomfort. Symptoms that may be associated with CK exposure include the following:

• In low doses
• • Bronchorrhea
  • Lacrimation
  • Rhinorrhea
• In high doses
• • Transient hyperpnea
  • Seizures 15-30 seconds later
  • Apnea 2-3 minutes later
  • Cardiac arrest 6-8 minutes postexposure
• Moderate range doses
• • Onset possibly takes several minutes, except for immediate irritant effects
  • Transient hyperpnea
  • Feelings of anxiety or apprehension
  • Vertigo
  • Nausea and/or vomiting
  • Prolonged prodrome prior to loss of consciousness
  • Seizures
  • Bradypnea followed by apnea
  • Cardiac arrest

Physical

Patients may suffer from any of the above symptoms. Physical findings are generally nonspecific and similar to those of severe hypoxemia.

• Severe prolonged exposure culminates in respiratory distress, convulsions, and apnea.
• Patients may have cherry red or pink skin because of concomitant carbon monoxide poisoning or because of cyanide-induced lack of extraction of oxygen at the tissue level and vasodilation. Arterialization of the venous blood also may be noted at phlebotomy or upon examination of the retinal veins. However, note that bright red skin or absence of cyanosis rarely is described. Cyanosis may be observed and most likely stems from concomitant cardiovascular collapse, seizures, or apnea. Finally, many cyanide victims have normal-appearing skin.
• Patients initially are hypertensive, tachypneic, and bradycardic, but eventually they become hypotensive. They may experience a transient tachycardia before spiraling into bradydysrhythmia that deteriorates into asystole.

Causes

Other than acts of terrorism or war, a mass casualty may develop in an industrial accident in which CK comes in contact with water (eg, during a fire-fighting expedition). Containers of CK may rupture or explode if exposed to high heat or following prolonged storage.

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Consider the diagnosis of CK poisoning in patients with irritation of the eyes, nose, and respiratory tract followed by rapid collapse or seizures, accompanied by metabolic acidosis and decreased oxygen consumption.
Other agents that may have similar features in toxicity include the following:
Methemoglobin-inducing agents
Carbon monoxide
Inert gases (simple asphyxiants)
Hydrogen sulfide
Azides
Arsine
Phosphine
Monomethylhydrazine
Isoniazid
Water hemlock
Strychnine
Organophosphates
Metformin

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Arterial and venous blood gases
• • Cyanide poisoning is characterized by a normal arterial PaO₂ despite symptoms of hypoxia and an abnormally high venous PO₂ (decreased arteriovenous oxygen [A-VO2] difference).
  • Victims of CK exposure may develop lowered PaO₂ due to irritant effects on the respiratory tract resulting in bronchospasm or pulmonary edema.
  • Depending on the severity of exposure, an arterial blood gas with a mixed respiratory and metabolic acidosis may be present. Metabolic acidosis is a hallmark of significant cyanide toxicity.
• Serum electrolytes, carbon dioxide, glucose, lactate level: A low carbon dioxide concentration and an elevated lactate level support the diagnosis.
• Cyanide levels: These levels generally are not available in time to guide acute treatment but may be confirmatory. The preferred test is an RBC cyanide level.
• Carboxyhemoglobin and methemoglobin levels: Obtain these levels, especially in victims of smoke inhalation. During treatment with sodium nitrite, observing methemoglobin levels over time may help to avoid toxic methemoglobinemia.

Other Tests

• Shortening of the ST segment with eventual fusion of the T wave into the QRS complex has been observed.

Procedures

• Depending on the severity of symptoms, endotracheal intubation may be necessary to optimize oxygen delivery and protect the airway.
• Fluorescein staining and slit lamp examination of the eyes may be necessary following decontamination to assess corneal integrity.

TREATMENT

Section 6 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Prehospital Care

• Remove victim from the cyanide source. Rescuers must have the highest level of respiratory protection (Level A).
• Give priority to decontamination of the eyes with water. Remove contaminated clothing and decontaminate the skin as appropriate with soap and water.
• Aggressive oxygenation, airway control, and supportive care with intravenous access and continuous cardiac monitoring are appropriate.
• Cyanide antidotes generally are not available in the prehospital setting but may be on hand at certain industrial sites. Administer antidotes as soon as possible in suggested or known cases of cyanide toxicity.

Emergency Department Care

• Continuation of hemodynamic support and optimization of oxygenation are the mainstays of treatment.
• If not performed at the scene, decontaminate patients by removing and isolating clothing and washing the patient from head to toe with soap and water. Avoid self-contamination of hospital workers. Following ocular decontamination, check for corneal integrity.
• Initiate antidote therapy with nitrites and sodium thiosulfate as soon as possible. Do not delay treatment for confirmatory RBC cyanide levels.
• Aggressive management of seizure activity with benzodiazepines is crucial.
• Consider gastric lavage and administration of charcoal in cases of recent cyanide ingestion. The gastric aspirate may cause secondary contamination and must be treated as hazardous.

Consultations

• Consult with law enforcement authorities and the Federal Bureau of Investigation (FBI) in any suspected terrorist incident.
• Consultation with a medical toxicologist and/or poison control center and intensivist may be useful.

MEDICATION

Section 7 of 11  

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• Differentials
• Workup
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• Follow-up
• Miscellaneous
• Multimedia
• References

The Pasadena (formerly Lilly) Cyanide Antidote Kit contains amyl nitrite, sodium nitrite, and sodium thiosulfate. Theoretically, the nitrite components oxidize iron contained in hemoglobin to methemoglobin. This creates an additional site for cyanide binding and promotes dissociation from cytochrome oxidase. Resultant cyanomethemoglobin then may be converted to less toxic thiocyanate through enzymes such as rhodanese or other sulfurtransferases in the presence of sodium thiosulfate. Only use amyl nitrite perles as a temporizing measure if IV access has not been established, since administration of IV sodium nitrite is more effective in creating therapeutic methemoglobin levels. Do not use sodium nitrite or use it only with extreme caution in the setting of concomitant carbon monoxide poisoning. However, in cases of smoke inhalation in which cyanide toxicity is suspected, administration of sodium thiosulfate is safe.

Unlike carbon monoxide, inhibition of cytochrome oxidase by cyanide is thought to be noncompetitive. Therefore, oxygen has only antidotal efficacy in human cyanide poisoning through uncertain mechanisms. Patients probably should be treated with at least 100% oxygen. Humidified oxygen may be beneficial to victims of CK inhalation who are experiencing airway irritation or those with significant signs of cyanide toxicity. In addition, inhaled beta2 agonists may be used to treat bronchospasm resulting from the irritant effects of CK on the respiratory tract.

Hyperbaric oxygen (HBO) use may be considered for patients with cyanide toxicity that is refractory to other antidotes, especially in the setting of concomitant carbon monoxide poisoning. However, its use in pure cyanide poisoning is controversial, since no human studies have been performed to date, although the animal data are intriguing. Ivanov showed in 1959 that HBO restored normal activity of the brain in mice poisoned with cyanide. In 1966, Skene demonstrated a drop in mortality from 96% to 20% in a group of mice treated with HBO at 2 atmosphere absolute (ATA) compared to those treated at 1 ATA. Finally, Takano showed in 1980 that HBO at 2 ATA reduced the pyridine nuclide fluorescence (which represents the degree of blockage of the respiratory chain) in the renal cortices of rabbits poisoned with cyanide.

Drug Category: Antidotes

Either directly counteract cyanide's toxicity on the electron transport chain or help the body eliminate the cyanide molecule.

Drug Category: Anticonvulsants

Cyanide inhibits brain glutamate decarboxylase, which causes a decrease in the inhibitory neurotransmitter GABA and contributes to convulsions. Drugs such as benzodiazepines or barbiturates, which act at the GABA receptor complex, therefore can help control seizures.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• Patients with symptoms beyond minor upper airway irritation and those with abnormal blood gases require admission to the hospital for continued monitoring and support.
• • Perform continuous cardiac monitoring.
  • Optimize oxygenation.
  • Monitor serum lactate levels and arterial and venous blood gases.
  • Monitor for delayed onset of pulmonary edema in those presenting with evidence of respiratory irritation.

Further Outpatient Care

• Reevaluate patients for neurologic sequelae 7-10 days after discharge from the hospital.

Transfer

• Should patients require transfer to a facility with the appropriate level of care, hemodynamically stabilize them prior to transfer. Transfer with an advanced cardiac life support (ACLS) level of service under continuous cardiac monitoring with supplemental oxygen and intravenous access. Assure cyanide antidote availability prior to transfer.

Complications

• Parkinsonlike syndromes and other neuropsychiatric sequelae are described in survivors of severe intoxication.

Prognosis

• Prognosis is better in patients with low-level exposures whose symptoms resolve after they are removed from exposure.

Patient Education

• For excellent patient education resources, visit eMedicine's Bioterrorism and Warfare Center and Poisoning Center . Also, see eMedicine's patient education articles Cyanide Poisoning, Chemical Warfare, Personal Protective Equipment, and Carbon Monoxide Poisoning.

MISCELLANEOUS

Section 9 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to consider cyanide toxicity in appropriate circumstances or treatment with oxygen alone

MULTIMEDIA

Section 10 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of North Carolina Statewide Program for Infection Control and Epidemiology (SPICE), copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html.
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REFERENCES

Section 11 of 11

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
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• Follow-up
• Miscellaneous
• Multimedia
• References

• Baud FJ, Barriot P, Toffis V, et al. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med. Dec 19 1991;325(25):1761-6. [Medline].
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• Ivanov KP. Effect of increased oxygen pressure on animals poisoned with potassium cyanide. Farmakol. Toksik. 1959;22:468-479.
• Jain KK. Cyanide poisoning. In: Textbook of Hyperbaric Medicine. 3rd ed. Seattle: Hogrefe and Huber;1999:182-184.
• Kindwall, EP. Carbon monoxide and cyanide poisoning. In: Hyperbaric Medicine Practice. 2nd ed. Arizona: Best Publishing Company;1995:363-372.
• Kurz P, Spingler B, Fox T. [TcI(CN)3(CO)3]2- and [ReI(CN)3(CO)3]2- :case studies for the binding properties of CN- and CO. Inorg Chem. Jun 28 2004;43(13):3789-91. [Medline].
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• Scolnick B, Hamel D, Woolf AD. Successful treatment of life-threatening propionitrile exposure with sodium nitrite/sodium thiosulfate followed by hyperbaric oxygen. J Occup Med. Jun 1993;35(6):577-80. [Medline].
• Shiono H, Maseda C, Akane A, Matsubara K. Rapid and sensitive quantitation of cyanide in blood and its application to fire victims. Am J Forensic Med Pathol. Mar 1991;12(1):50-3. [Medline].
• Skene WG, Norman JN, Smith G. Effect of hyperbaric oxygen in cyanide poisoning. Proceedings of the Third International Congress on Hyperbaric Medicine. 1966:705-710.
• Tabrah FL, Tanner R, Vega R, Batkin S. Baromedicine today--rational uses of hyperbaric oxygen therapy. Hawaii Med J. Apr 1994;53(4):112-5, 119. [Medline].
• Takano T, Myazaki Y. Effect of hyperbaric oxygen on cyanide intoxication: In situ changes in intracellular oxidation reduction. Undersea and Baromed Res. 1980;7:191-7.
• Tomaszewski CA, Thom SR. Use of hyperbaric oxygen in toxicology. Emerg Med Clin North Am. May 1994;12(2):437-59. [Medline].
• Way JL, End E, Sheehy MH, et al. Effect of oxygen on cyanide intoxication. IV. Hyperbaric oxygen. Toxicol Appl Pharmacol. Jul 1972;22(3):415-21. [Medline].
• Zheng A, Dzombak DA, Luthy RG. Formation of free cyanide and cyanogen chloride from chloramination of publicly owned treatment works secondary effluent: laboratory study with model compounds. Water Environ Res. Mar-Apr 2004;76(2):113-20. [Medline].

Article Last Updated: Jun 13, 2006