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

Cyanide, one of the most rapidly acting lethal poisons known to humankind, was a main constituent of Earth's primordial atmosphere and probably played an important role in the development of life on Earth. It exists in nature in many different forms and may be found in a number of fruits and vegetables in the form of cyanogenic glycosides.

Cyanide can be a gas, liquid, or solid and may exhibit a faint bitter almondlike odor. Cyanide may be combined with salts (eg, sodium, calcium, potassium), metals (eg, cobalt, zinc, gold, mercury), and halides (eg, chloride, fluoride, iodide, bromide) or with organic acids to form nitriles.

Cyanide is used in many industries, including electroplating, pigment production, metallurgy (eg, electroplating, case hardening), chemical production, photographic development, plastic production, ship fumigation, and some mining processes, such as gold extraction. Cyanide is also used in agriculture (eg, soil sterilization) and leather processing (eg, removing hair from hides). Cyanogenic amides are used as fertilizers, and cyanogenic halides are used in chemical synthesis. The nitriles, or organic cyanides, are used in the synthesis of flame-resistant fibers, plastics, and rubber. Hydrogen cyanide is also used as an insecticide and in the fumigation of large rat- and insect-infested ships and dwellings.

Currently in the US, cyanide poisoning is most commonly seen in the setting of a fire in an enclosed space or as a result of an accidental exposure to the chemical at work. Cyanide suicides and homicides have also been reported.

Pathophysiology

Cyanide poisoning occurs when a cyanogenic substance is ingested, inhaled, smoked or absorbed through the skin. Exposure to only small amounts of the toxin can result in serious poisoning and death. Cyanide readily and reversibly binds to all enzymes and proteins that contain iron (including hemoglobin, myoglobin, catalase, and the cytochrome system) and those containing cobalt.

Cyanide's main pathological effects derive from its interaction with the cytochrome aa3 complex. When bound to the iron moiety of the cytochrome, it inhibits oxidative phosphorylation and paralyzes cellular respiration. This results in anaerobic metabolism, increased lactic acid production, reduced ATP stores, and anoxic cell death. The organ systems that are most sensitive to cyanide toxicity are those with the highest oxygen use that cannot tolerate hypoxic stress, namely the CNS and the myocardium.

Information on the pharmacokinetic properties of cyanide is scarce; most information was obtained from animal studies and a few human poisoning cases. When inhaled, gaseous cyanide produces symptoms within seconds and death occurs within minutes. When ingested, cyanide salts produce symptoms within minutes; death occurs within minutes to hours. The ingestion of cyanogenic fruits, on the other hand, is associated with a delayed onset of toxicity. The fruit pits, which contain amygdalin, also contain emulsin, an enzyme that is capable of hydrolyzing amygdalin to release hydrogen cyanide. Emulsin is much more effective in alkaline pH and, hence, in the intestinal tract rather than in the acidic environment of the stomach. Consequently, persons who ingest cyanogenic fruits and plants may present several hours after ingestion.

Once absorbed, cyanide is 60% protein-bound and has a volume of distribution of approximately 0.5 L/kg. The half-life for the conversion of cyanide to thiocyanate from a nonlethal dose in humans is between 20 minutes and 1 hour. Cyanide is nearly completely metabolized by rhodanese (sulfurtransferase), to inactive compounds prior to excretion, and only a small portion is excreted unchanged in the lungs and sweat. Rhodanese is a sulfurtransferase that catalyzes the combination of cyanide with sulfur to form thiocyanate, a much less toxic compound that is readily excreted in the urine. Hydrogen cyanide may also be converted to a nontoxic compound by its combination with hydroxocobalamin (vitamin B-12a), which produces cyanocobalamin (vitamin B-12).

Frequency

United States

In the United States, cyanide poisoning occurs most commonly in the setting of fire and smoke in an enclosed space. Intentional use and work-related accidents are also commonly reported. In 2004, 257 cases of cyanide poisoning were reported to various poison control centers of the US with 8 fatalities. Thirty two of the 257 cases were intentional.

International

Similar to the United States, cyanide poisoning in Europe and Australia is most commonly reported in the setting of smoke inhalation and as a result of industrial accidents.

Worldwide, a number of industrial accidents involving the release of cyanide into the environment have occurred over the past decade. Massive river spills with extensive and disastrous environmental impact have occurred in Danube tributaries and in rivers in Ghana, China, Ecuador, and Nicaragua. In some cases, these spills have caused human illness and death. In June 2005, for example, at least 60-100 villagers were poisoned by drinking water downstream of a cyanide spill from a gold mine in Laos. Similar incidents left more than a hundred people hospitalized in Taiwan, and killed 12 children in Nicaragua, and 3 people in China. 

Mortality/Morbidity

The average fatal adult dose of hydrogen cyanide is 50-60 mg (1.1 mg/kg). The oral median lethal dose for sodium and potassium cyanide is estimated at 2 mg/kg. Exposure to airborne concentrations of 90 parts per million (ppm) for 30 minutes or more is likely to be incompatible with life, although death may result from a few minutes of exposure at 300 ppm.

Serious poisoning has occurred with ingestions of as little as 50 mg of potassium cyanide, and death has been reported in adults following the ingestion of 200-300 mg of potassium cyanide. Conversely, patients who have ingested 1 g of cyanide have survived.

Sex

Deliberate self-poisonings and industrial accidents tend to occur predominantly in adult men. Cyanide poisoning in pregnant women may have teratogenic effects on the fetus. Cyanide poisoning has been shown to cause resorptions and malformations in the offspring of animals in experiments.

Age

Deliberate self-poisoning and industrial accidents occur predominantly in adult men.

CLINICAL

Section 3 of 11  

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

History

Cyanide is one of the most rapidly acting of all known poisons. Inhalation of a lethal dose may cause loss of consciousness within a few breaths and death within a few minutes. Persons who ingest cyanide salts become symptomatic within minutes and may die within 30 minutes. Similarly, persons with smoke inhalation may die within minutes of inhalation. The ingestion of cyanogenic plants may not manifest as toxicity until 1.5-2 hours after the ingestion, and, in the case of ingestion of cyanogenic glycosides, these manifestations may not be apparent until a few hours after ingestion.

Prompt recognition of cyanide poisoning is crucial; however, the signs and symptoms of acute cyanide poisoning are often nonspecific. The health care provider must maintain a high index of suspicion. Given the right setting, cyanide poisoning should be considered in the differential diagnoses of sudden death, sudden global neurologic deficit (ie, coma, convulsions, encephalopathy), severe acidosis, and shock.

People at risk for cyanide poisoning include persons with smoke inhalation, chemistry laboratory personnel, and employees of a number of industries that use cyanogenic substances. These include gold and silver extraction, leather tanning, photographic development, semiconductor production, petrochemical industries, and fumigation industries.

Poisoning at home may occur from the inhalation of metal-cleaning solutions, photographic development solutions, or gold and silver extraction solutions. Poisoning at home also may occur after the unsuspecting ingestion of cyanogenic plants, after an intentional ingestion of Laetrile (most common in persons with cancer), or after the accidental ingestion of artificial nail polish removers or rodenticides (most common in children).

Finally, cyanide poisoning may occur in the hospital during infusions of sodium nitroprusside and should be considered in patients who suddenly become agitated, become comatose, develop convulsions, or become acidotic.

Patients who have survived an ingestion of cyanide report burning of the tongue and throat upon deglutition. Patients may experience asthenia, loss of energy, pain throughout the body, headache, dizziness, chest pain, palpitations, cough, shortness of breath, nausea, and vomiting. These may be followed by confusion, agitation, convulsions, paralysis, coma, and death.

Physical

The physical examination findings are scarce and otherwise nonspecific in a person with cyanide poisoning. The time to onset of symptoms and the severity of symptoms depend on the dose and route of cyanide exposure. Coma, tonic-clonic seizures, cyanosis, shock, and severe metabolic acidosis reflect a serious overdose that requires prompt institution of therapy.

Helpful clues that help diagnose cyanide poisoning include a lack of cyanosis in patients who are still breathing and equally red retinal arteries and veins upon funduscopic examination. Both of these findings are due to the tissue's inadequate oxygen use. The odor of bitter almonds emanating from the patient can be an additional clue to help diagnose cyanide poisoning; however, up to 40% of the population is unable to detect this odor. The presence of soot in the mouth and nose of a patient with smoke inhalation who is comatose should also raise suspicion of cyanide toxicity, particularly if the patient is acidotic or hypotensive.

Additional findings from the physical examination are generally nonspecific and noncontributory. The patient may exhibit tachypnea, bradypnea, tachycardia, bradycardia, hypoxia, hypotension, and shock. The pupils may be dilated and reactive, and the cornea may be edematous. Patients involved in fires or who have experienced smoke inhalation may also experience thermal and chemical injury to the lungs resulting in pulmonary damage, noncardiogenic pulmonary edema, hypoxia, cyanosis, and, ultimately, death.

Causes

• Smoke inhalation
• • Cyanide poisoning is a major factor that contributes to death due to smoke inhalation.
  • During fires, the incomplete combustion of nitrogen-containing organic compounds may generate hydrogen cyanide. These compounds include cotton, rayon, wool, polyvinyl chloride, modacrylic, polyurethane foam, polyester wadding, neoprene foam, paper, asphalt, nylon, rubber, plastics, Styrofoam, and insulation resins. Poisoning occurs if the hydrogen cyanide concentration is high, ie, if the fire occurs in an enclosed space.
• Occupational exposure
• • Dupont is the only company in the United States that produces cyanide products.
  • Occupations in which cyanides are used include fumigation of ships and dwellings, partial soil sterilization, and fumigation intended to kill agricultural parasites. Chemistry laboratories may also use cyanide.
  • Some occupations may use or produce compounds that release cyanide under certain conditions. Occupations and industry examples include the petrochemical industry, the manufacture of blast-furnaces, illuminating gas works, coke ovens, the extraction of phosphoric acid from bones, gold and silver leaching, electroplating, metal cleaning, synthetic fiber (eg, acetonitrile, acrylonitrile, glyconitrile) and rubber synthesis, photography, and the leather-treatment industry.
• Industrial accidents
• • Accidental leakage of cyanide into the environment is another major source of poisoning of wildlife and humans. Areas of accidental cyanide spills biologically die within a short time.
  • Gold-mining companies that use cyanide leaching to extract gold from ore have been responsible for a number of industrial accidents in the United States and abroad.
• Foods
• • A number of plants contain cyanogenic glycosides, which are substances that release cyanide when hydrolyzed in the GI tract. These cyanogenic glycosides include amygdalin, linamarin, and dhurrin.
  • Amygdalin is found in variable amounts in the flowers, leaves, and seeds of the Prunus, plants, eg, peaches, plums, apricots, bitter almonds, chokecherries, and cherry laurels. Amygdalin is also a component of Laetrile, the once-popular cancer drug. Other plants that contain amygdalin include apple and pear seeds, linseeds, elderberry, bamboo, corn, sweet potatoes, and millet.
  • Cassava (yucca) and certain lima beans contain linamarin, another cyanogenic glycoside. Cassava has been implicated in a number of cases of acute and chronic cyanide poisoning throughout the world.
  • Dhurrin, which is found in sorghum grass, has been implicated in a number of poisonings in grazing animals.
• Intentional suicidal or homicidal ingestions
• • Potassium cyanide is the most commonly used cyanide-based agent in self-poisonings and was the agent used to poison and kill 913 followers of the Reverend Jim Jones in 1978.
  • Cyanide continues to be an agent of choice in criminal tampering of drugs, water, and food products.
• Iatrogenic
• • Sodium nitroprusside (Na₂-Fe-(CN)5-NO-2H₂O) is a rapidly acting and potent vasodilator that is commonly used in hypertensive emergencies and to treat some forms of cardiac failure.
  • In addition to sodium and water, sodium nitroprusside is composed of 1 nitroso moiety, 1 iron molecule, and 5 cyanide molecules. Sodium nitroprusside is rapidly taken up by hemoglobin and metabolized into nitric oxide and cyanogen (an unstable cyanide radical). Most of the cyanide molecules thus released (4 of 5) are then combined with sulfhydryl groups to form the less toxic thiocyanate, which is then excreted in the urine. The reaction is catalyzed by the hepatic enzyme rhodanese, a sulfhydryl transferase whose function depends on the availability of sulfur groups. It is the rate-limiting step in the detoxification of nitroprusside, but its activity may be augmented by an exogenous supply of sulfur groups (usually accomplished by sodium thiosulfate).
  • Nitroprusside in large doses or rapid and prolonged infusions can overwhelm rhodanese and result in a buildup of cyanide, causing cyanide toxicity.
  • Similarly, large doses of nitroprusside can result in a buildup of thiocyanate, especially in patients with renal failure. Although less toxic than cyanide, high concentrations of thiocyanate are poisonous. Symptoms of thiocyanate toxicity are manifested by unexplained abdominal pain, convulsions, and other manifestations of CNS injury.
  • The exact nitroprusside infusion rate at which cyanide toxicity occurs is debated. Cyanide levels rise dramatically with infusion rates greater than 1-2 mcg/kg/min. Cyanide toxicity has been reported with nitroprusside infusion rates that exceed 4 mcg/kg/min for as little as 2 hours. Therefore, infusion rates greater than 4 mcg/kg/min are not recommended for prolonged periods. Similarly, infusion rates of 10 mcg/kg/min are not advised for longer than 10 minutes.
  • The maximum recommended total dose of nitroprusside is also debated. Most investigators recommend a maximum dose of 1.5 mg/kg for infusions that last 1-3 hours, but some authors allow up to 3-3.5 mg/kg.
  • Nitroprusside-associated cyanide poisoning is rare but occurs most commonly in patients with hepatic failure, persons with decompensated congestive heart failure with passive liver congestion, or in patients receiving high doses or rapid and prolonged infusions of the drug. Patients may experience dyspnea, chest pain, headache, dizziness, and vomiting. The earliest sign may be a decline in hemodynamic status following an initial favorable response to the drug. Other signs include anxiety, agitation, hyperventilation, acidosis, syncope, convulsions, coma, circulatory collapse, and death.
  • Current laboratory methods for monitoring cyanide toxicity during nitroprusside infusions are not specific. Cyanide toxicity is first manifested by an increase in mixed venous PO₂ or a narrowed arteriovenous oxygen difference, especially when a decline in cardiac output occurs after an initial improvement. As anaerobic metabolism increases, base excess and lactate levels rise. A falling pH level heralds cardiovascular collapse.
• Cigarettes
• • Cigarette smoking commonly releases cyanide. Persons who smoke tobacco have a mean blood cyanide level of 0.4 mcg/mL, which is 2.5 times greater than the level in persons who do not smoke.
  • Long-term low-dose cyanide poisoning is thought to be the cause of tobacco amblyopia and has been associated with Leber hereditary optic atrophy.

DIFFERENTIALS

Section 4 of 11  

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

Other Problems to be Considered

Included in the differential diagnoses are the asphyxiant gases (eg, carbon dioxide, nitrogen, methane, carbon monoxide, hydrogen cyanide, hydrogen sulfide) and the respiratory irritant gases (eg, ammonia, chlorine, ozone, phosgene, sulfur dioxide, oxides of nitrogen). Sodium azide poisoning, acute radiation poisoning, and hemlock poisoning also may manifest as acute CNS failure followed by cardiac arrest. Other causes of increased anion gap acidosis must be sought and excluded, including diabetic ketoacidosis, methanol toxicity, ethylene glycol toxicity, iron poisoning, and isoniazid overdose.

WORKUP

Section 5 of 11  

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

Lab Studies

• Cyanide levels
• • Techniques for the direct measurement of blood cyanide levels are not widely available, thus making the immediate laboratory confirmation of cyanide toxicity not possible in most instances. The diagnosis of cyanide toxicity must, therefore, be based on clinical suspicion and rely on indirect evidence of poisoning. Additionally, no clear evidence has established a dose and effect relation between cyanide level and human toxicity.  Serum cyanide levels exceeding 0.5 mg/L are toxic, and levels greater than 2.6 mg/dL (100 micromol/L) are generally lethal.
  • Because of its inhibitory effects on cellular respiration, cyanide poisoning generally results in profound lactic acidosis. Blood pH and lactate concentrations may, therefore, be used as aids in the evaluation of patients with cyanide toxicity. When smoke inhalation is excluded, a plasma lactate concentration of greater than 8 mmol/L (72 mg/dL) appears to have a positive correlation with a blood cyanide concentration of greater than 1 mg/L. In a study by Baud et al, for example, a plasma lactate concentration of 72 mg/dL per liter (8 mmol/L) or higher was 94% sensitive and 70% specific for a blood cyanide concentration of greater than 1 mg/L.¹ The specificity rose to 85% when patients receiving catecholamines were excluded.
• Blood gases
• • The PaO₂ level and the co-oximeter-measured arterial oxygen saturation remain relatively normal in patients who are ventilated.
  • The central venous PO₂ level and measured mixed venous oxygen saturation are elevated in persons with cyanide poisoning because tissues are unable to extract oxygen. This results in a reduced arteriovenous oxygen difference.
  • The arterial blood gas demonstrates significant metabolic acidosis.
• Serum lactate
• • The serum lactate level is elevated because of anaerobic metabolism.
  • Lactate levels of greater than 6 mmol/L in patients who ingested a cyanogenic compound suggest a significant poisoning.
  • Lactate levels of greater than 8 mmol/L may serve as a cutoff level to increase the diagnostic suspicion for significant cyanide poisoning.
  • Lactate levels of greater than 10 mmol/L in patients with smoke inhalation should raise suspicion of cyanide poisoning.
• Hemoglobin
• • The hemoglobin level must be optimized in all patients so that adequate oxygen delivery may continue.
  • The hemoglobin level is also used to calculate the amount of antidotal therapy needed.
• Carboxyhemoglobin
• • Carboxyhemoglobin measurements are necessary in all patients with smoke inhalation because these measurements may dictate hyperbaric oxygen (HBO) therapy and contraindicate the induction of methemoglobinemia in the treatment of cyanide poisoning.
  • In the presence of carboxyhemoglobinemia, the induction of methemoglobinemia results in further reduction in the oxygen-carrying capacity of the blood and should be performed with extreme caution, if at all.
• Methemoglobin: levels of methemoglobin must be maintained below 30% at all times, especially during antidotal therapy.
• Electrolytes: Measurement of the anion gap may give clues to the presence of lactic acidosis.

Imaging Studies

• Chest radiographs may demonstrate the presence of noncardiogenic pulmonary edema or may show signs of atelectasis or aspiration pneumonia.
• CT scan of the brain shows evidence of hypoxic brain injury, especially the basal ganglia.

Other Tests

• Electrocardiogram
• • Electrocardiographic changes are generally attributed to hypoxic injury and may include sinus bradycardia and tachycardia, atrial fibrillation, ectopic ventricular beats, dysrhythmias, widened QRS complexes, ST elevation or depression, QT prolongation, and T-wave inversion.
  • Sinus bradycardia is a common presenting ECG rhythm early in the course of poisoning.

TREATMENT

Section 6 of 11  

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

Medical Care

The timely infusion of the antidote is crucial to the survival of cyanide poisoned patients. Supportive therapy, however, remains extremely important as it has been successful in reversing critical illness in patients poisoned with cyanide, but in whom the etiology was not recognized and to whom the antidote was not administered. Supportive therapy may include endotracheal intubation, mechanical ventilation, normobaric oxygen therapy, hyperbaric oxygen therapy, volume resuscitation, hemodynamic support as well as decontamination.

One should have a low threshold for admission to the intensive care unit. Absolute indications for admission include all patients who require endotracheal intubation, all comatose patients, all patients who develop seizures or other serious symptoms, and patients with cardiovascular instability.

Antidote therapy

Cyanide antidotes may be classified into 3 main categories depending on whether they provide cobalt groups, induce methemoglobinemia, or provide sulfhydryl groups.  Cobalt-based antidotes, take advantage of the cyanide's affinity for cobalt. The most commonly used cobalt compounds are hydroxocobalamin (Europe) and dicobalt edetate (Great Britain). Methemoglobin-based antidotes take advantage of its affinity for ferric ion. They include amyl nitrite and sodium nitrite, both found in the cyanide antidote kit, (USA) and 4-dimethylaminophenol (Europe).  Sulfhydryl donors, on the other hand, promote detoxification of cyanide by inducing enzymatic degradation of cyanomethemoglobin complexes.

Other detoxification mechanisms have also been proposed.  Hydroxocobalamin appears to impart the best survival benefit with the least side effects in victims of cyanide poisoning. Methemoglobin-based antidotes have a number of disadvantages, especially in victims of smoke inhalation.  These are mainly due to the inability of methemoglobin to carry oxygen. As to sulfhydryl donors, their onset of action is too slow for use in the emergency and critical care setting.

• Hydroxocobalamin, a natural form of vitamin B12, has been used in Europe, and specifically in France since 1996, but was not approved for use in the US by the FDA until 2006. It directly chelates and fixes cyanide to form cyanocobalamin (vitamin B-12). Cyanocobalamin is nontoxic and is readily eliminated in the urine. Hydroxy cobalamine has been successfully used for cyanide toxicity from any source including smoke inhalation, and nitroprusside infusion. The dose used is high (5 g) but appears to be well tolerated by patients and has few side effects. Cyanide levels, however, may remain elevated during hydroxocobalamin infusion.
• Methemoglobin-based cyanide detoxification consists of 2 phases of drug administration, as follows:  
• • Phase 1 consists of the induction of methemoglobinemia so that so that cyanide, which has a high affinity for the ferric iron (Fe₃⁺), attaches to methemoglobin, rather than to the ferric ion of the cytochrome, thereby restoring cellular respiration. Methemoglobinemia can be induced in a number of ways. These include the inhalation of amyl nitrite pearls, the intravenous infusion of sodium nitrite, or 4-dimethylaminophenol (DMAP).
  • In phase 2 of cyanide detoxification, the cyanomethemoglobin thus formed, is detoxified by the infusion of sodium thiosulfate. Sodium thiosulfate functions as a sulfhydryl donor to rhodanese, the enzyme that catalyzes the detoxification of cyanomethemoglobin. In the presence of sodium thiosulfate, rhodanese catalyzes the formation of thiocyanate, a nontoxic substance that is rapidly excreted in the urine.

These antidotes are particularly deleterious in the presence of carboxyhemoglobin and sulfhemoglobin, as these do not carry oxygen, either. Methemoglobin-based antidotes are, therefore, less useful in cyanide poisoning due to smoke inhalation. Another disadvantage of methemoglobin-based antidotes is the requirement for close monitoring of the methemoglobin level, which must be kept below 30%. Severe methemoglobinemia may arise in patients who require multiple doses of sodium nitrite infusion, such as patients poisoned by aliphatic nitriles (eg, children who ingest artificial nail polish removers) and patients with an incomplete clinical response to the first dose.

Consultations

• Toxicologist
• Hyperbaric therapist

MEDICATION

Section 7 of 11  

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

The goals of pharmacotherapy are to neutralize the toxic agent, to prevent complications, and to reduce morbidity.

Drug Category: Cobalt Compounds

Cobalt has great affinity for cyanide and is known to form a stable complex with cyanide, thus freeing the cytochrome oxidase system. Cobalt ions may also reactivate cyanide-poisoned cytochromes. Hydroxocobalamin binds to cyanide to form cyanocobalamin (Vitamin B12), which is excreted in the urine. Hydroxocobalamin appears to be the safest, effective antidote, and is only associated with minor, transient side effects.

Drug Category: Cobalt compounds

Cobalt has great affinity for cyanide and is known to form a stable complex with cyanide, thus freeing the cytochrome oxidase system. Cobalt ions may also reactivate cyanide-poisoned cytochromes. 

Drug Category: Methemoglobin inducers

The rationale for using methemoglobin inducers in cyanide poisoning is based on the ferric iron ability of methemoglobin to bind cyanide, thus freeing the cytochrome and allowing aerobic cellular respiration to continue. In the United States, the most commonly used methemoglobin inducers are nitrites, whereas, in Europe, DMAP is commonly used to induce methemoglobinemia rapidly and, thus, attenuate cyanide toxicity. DMAP is currently not available in the United States.

Cyanide detoxification is generally accomplished with rhodanese, an enzyme that catalyzes the irreversible transfer of a sulfone group to cyanide. While a number of sulfone donors exist in the body, an exogenous source of sulfone groups is generally provided to ensure that cyanide is quickly detoxified and excreted.

Drug Category: Alkalinizing agents

Hemodynamic support, maintenance of adequate blood pressure, and correction of blood pH are of paramount importance in the management of cyanide toxicity. Metabolic acidosis must be corrected with sodium bicarbonate when the blood pH level falls below 7.15.

Drug Category: Inotropes

Hypotension is treated with judicious infusions of crystalloids. If unsuccessful, inotropes must be initiated.

Drug Category: Anticonvulsants

Convulsions are controlled with benzodiazepines and, if unsuccessful, barbiturates or phenytoin.

Drug Category: Gastrointestinal decontaminants

These agents reduce absorption toxic chemicals from GI tract.

FOLLOW-UP

Section 8 of 11  

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

Transfer

• Transfer to a hyperbaric chamber may be indicated when the patient is stabilized. HBO therapy is indicated for patients who do not respond to supportive and antidotal therapy and for patients with smoke inhalation who have carboxyhemoglobinemia.
• Patients may be transferred to a nonmonitored bed when their symptoms have resolved and complications have been treated.
• Transfer to a psychiatric inpatient unit may be required for patients who ingested cyanide as a suicide attempt.

Deterrence/Prevention

• Compliance with US Occupational Safety and Health Administration (OSHA) regulations in the workplace
• Psychiatric support for patients with suicidal intent
• Patient education regarding the cyanogenic content of certain plants and compounds
• Carbon monoxide monitors and fire alarms

Complications

• Complications of acute cyanide poisoning are commonly due to anoxia and hypoxia.
• In patients with chronic sublethal exposure to cyanide, a number of complications have been noted, including peripheral demyelination of the nerves, resulting in neuropathies.
• Patients may exhibit ataxia because of spinal sensory nerve involvement, deafness, and optic nerve atrophy.
• Tobacco amblyopia has been ascribed to chronic elevations of cyanide levels in persons who smoke heavily and is associated with a deficiency of vitamin B-12.

Prognosis

• The prognosis of acute cyanide poisoning depends on the timely institution of supportive and antidotal therapy.
• • Patients who receive timely therapy have an excellent prognosis with few sequelae.
  • Patients who have sustained anoxic encephalopathy and cardiac arrest have a poor prognosis.
  • Additionally, the development of other complications, such as myocardial infarction and aspiration pneumonitis, may adversely affect the patient's prognosis.

Patient Education

For excellent patient education resources, visit eMedicine's Poisoning Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Poisoning, Cyanide Poisoning, Activated Charcoal, 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 diagnose cyanide poisoning
• Failure to administer the antidote when indicated
• Failure to follow the manufacturer's directions for administration of therapy
• Failure to monitor for the adverse effects of therapy
• Failure to correct methemoglobinemia if it becomes symptomatic
• Failure to maximize supportive therapy

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.
	View Full Size Image
Media type:  Image

REFERENCES

Section 11 of 11

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

1. 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].
2. Alcorta R. Smoke inhalation & acute cyanide poisoning. Hydrogen cyanide poisoning proves increasingly common in smoke-inhalation victims. JEMS. Aug 2004;29(8):suppl 6-15; quiz suppl 16-7. [Medline].
3. Barillo DJ, Goode R, Esch V. Cyanide poisoning in victims of fire: analysis of 364 cases and review of the literature. J Burn Care Rehabil. Jan-Feb 1994;15(1):46-57. [Medline].
4. Baud FJ, Borron SW, Bavoux E, et al. Relation between plasma lactate and blood cyanide concentrations in acute cyanide poisoning. BMJ. Jan 6 1996;312(7022):26-7. [Medline].
5. Baud FJ, Borron SW, Megarbane B, et al. Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Crit Care Med. Sep 2002;30(9):2044-50. [Medline].
6. Bismuth C, Baud FJ, Djeghout H, et al. Cyanide poisoning from propionitrile exposure. J Emerg Med. May-Jun 1987;5(3):191-5. [Medline].
7. Borron SW, Baud FJ. Reply to: "Is hydroxocobalamin safe and effective for smoke inhalation? Searching for guidance in the haze". Ann Emerg Med. Jan 2008;51(1):109-10; author reply 110-1. [Medline].
8. Borron SW, Baud FJ, Barriot P, et al. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. Jun 2007;49(6):794-801, 801.e1-2. [Medline].
9. Borron SW, Baud FJ, Megarbane B, et al. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg Med. Jun 2007;25(5):551-8. [Medline].
10. Borron SW, Uhl W, Nolting A, et al. Interference of the cyanide antidote hydroxocobalamin with carboxyhemoglobin measurements should not limit clinical use in suspected or confirmed cyanide poisoning. Ann Emerg Med. Nov 2007;50(5):624-5; author reply 626. [Medline].
11. Braico KT, Humbert JR, Terplan KL, et al. Laetrile intoxication. Report of a fatal case. N Engl J Med. Feb 1 1979;300(5):238-40. [Medline].
12. Brouard A, Blaisot B, Bismuth C. Hydroxocobalamine in cyanide poisoning. J Toxicol Clin Exp. May-Jun 1987;7(3):155-68. [Medline].
13. Cottrell JE, Casthely P, Brodie JD, et al. Prevention of nitroprusside-induced cyanide toxicity with hydroxocobalamin. N Engl J Med. Apr 13 1978;298(15):809-11. [Medline].
14. Eckstein M. Cyanide as a chemical terrorism weapon. JEMS. Aug 2004;29(8):suppl 22-31. [Medline].
15. Fortin JL, Ruttiman M, Domanski L, et al. Hydroxocobalamin: treatment for smoke inhalation-associated cyanide poisoning. Meeting the needs of fire victims. JEMS. Aug 2004;29(8):suppl 18-21. [Medline].
16. Gill JR, Marker E, Stajic M. Suicide by cyanide: 17 deaths. J Forensic Sci. Jul 2004;49(4):826-8. [Medline].
17. Hall AH. Systemic asphyxiants. In: Irwin RS, Cerra FB, Rippe JM, eds. Irwin & Rippe's Intensive Care Medicine. 4^th ed. Baltimore, Md: Lippincott Williams & Wilkins; 1999:1797-9.
18. Hall AH, Dart R, Bogdan G. Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning?. Ann Emerg Med. Jun 2007;49(6):806-13. [Medline].
19. Hall AH, Linden CH, Kulig KW, et al. Cyanide poisoning from laetrile ingestion: role of nitrite therapy. Pediatrics. Aug 1986;78(2):269-72. [Medline].
20. Hall AH, Rumack BH. Clinical toxicology of cyanide. Ann Emerg Med. Sep 1986;15(9):1067-74. [Medline].
21. Hall VA, Guest JM. Sodium nitroprusside-induced cyanide intoxication and prevention with sodium thiosulfate prophylaxis. Am J Crit Care. Sep 1992;1(2):19-25; quiz 26-7. [Medline].
22. Holstege CP, Isom G, Kirk MA. Cyanide and hydrogen sulfide. In: Goldfrank's Toxicologic Emergencies. Lewis Goldfrank, Neal Flomenbaum, Neal Lewis, Mary Ann Howland, Robert Hoffman, Lewis Nelson. 8th Edition. McGraw Hill Companies, Inc.; 2006:1712-1725.
23. Howland MA. Sodium and Amyl Nitrites. In: In Goldfrank's Toxicologic Emergencies. Lewis Goldfrank, Neal Flomenbaum, Neal Lewis, Mary Ann Howland, Robert Hoffman, Lewis Nelson. 8th Edition. 8th. McGraw Hill Companies, Inc.; 2006:1725-1727.
24. Howland MA. Sodium Thiosulfate. In: In Goldfrank's Toxicologic Emergencies. Lewis Goldfrank, Neal Flomenbaum, Neal Lewis, Mary Ann Howland, Robert Hoffman, Lewis Nelson. 8th Edition. McGraw Hill Companies, Inc. 8th. 2006:1728-1730.
25. Howland MA. Hydroxycobalamin. In: In Goldfrank's Toxicologic Emergencies. Lewis Goldfrank, Neal Flomenbaum, Neal Lewis, Mary Ann Howland, Robert Hoffman, Lewis Nelson. 8th Edition. McGraw Hill Companies, Inc. 8th. 2006:1731-1733.
26. Kulig K. Cyanide antidotes and fire toxicology. N Engl J Med. Dec 19 1991;325(25):1801-2. [Medline].
27. Mueller M, Borland C. Delayed cyanide poisoning following acetonitrile ingestion. Postgrad Med J. May 1997;73(859):299-300. [Medline].
28. Pasch T, Schulz V, Hoppelshauser G. Nitroprusside-induced formation of cyanide and its detoxication with thiosulfate during deliberate hypotension. J Cardiovasc Pharmacol. Jan-Feb 1983;5(1):77-85. [Medline].
29. Posner MA, Rodkey FL, Tobey RE. Nitroprusside-induced cyanide poisoning: antidotal effect of hydroxocobalamin. Anesthesiology. Apr 1976;44(4):330-5. [Medline].
30. Price D. Methemoglobin Inducers. In: In Goldfrank's Toxicologic Emergencies. Lewis Goldfrank, Neal Flomenbaum, Neal Lewis, Mary Ann Howland, Robert Hoffman, Lewis Nelson. 8th Edition. McGraw Hill Companies, Inc.; 2006:1734-1745.
31. Rella J, Marcus S, Wagner BJ. Rapid cyanide detection using the Cyantesmo kit. J Toxicol Clin Toxicol. 2004;42(6):897-900. [Medline].
32. Robin ED, McCauley R. Nitroprusside-related cyanide poisoning. Time (long past due) for urgent, effective interventions. Chest. Dec 1992;102(6):1842-5. [Medline].
33. Salkowski AA, Penney DG. Cyanide poisoning in animals and humans: a review. Vet Hum Toxicol. Oct 1994;36(5):455-66. [Medline].
34. Schulz V. Clinical pharmacokinetics of nitroprusside, cyanide, thiosulphate and thiocyanate. Clin Pharmacokinet. May-Jun 1984;9(3):239-51. [Medline].
35. Vesey CJ, Cole PV. Blood cyanide and thiocyanate concentrations produced by long-term therapy with sodium nitroprusside. Br J Anaesth. Feb 1985;57(2):148-55. [Medline].
36. Walsh DW, Eckstein M. Hydrogen cyanide in fire smoke: an underappreciated threat. Emerg Med Serv. Oct 2004;33(10):160-3. [Medline].
37. Watson WA, Litovitz TL, Klein-Schwartz W, et al. 2003 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med. Sep 2004;22(5):335-404. [Medline].
38. Way JL. Cyanide intoxication and its mechanism of antagonism. Annu Rev Pharmacol Toxicol. 1984;24:451-81. [Medline].
39. Way JL, Tamulinas CB, Leung P, et al. Pharmacologic and toxicologic basis of cyanide antagonism. Proc West Pharmacol Soc. 1984;27:149-53. [Medline].
40. Weng TI, Fang CC, Lin SM, et al. Elevated plasma cyanide level after hydroxocobalamin infusion for cyanide poisoning. Am J Emerg Med. Oct 2004;22(6):492-3. [Medline].
41. Yen D, Tsai J, Wang LM, et al. The clinical experience of acute cyanide poisoning. Am J Emerg Med. Sep 1995;13(5):524-8. [Medline].

Article Last Updated: Aug 12, 2008