Cyanide is a rapidly acting substance that is traditionally known as a poison. Hydrogen cyanide was first isolated from Prussian blue dye in 1786 and cyanide first extracted from almonds around 1800. Cyanide can exist as a gas, hydrogen cyanide, a salt, potassium cyanide. Natural substances in some foods such as lima beans, almonds can release cyanide. Cyanide is also found in manufacturing and industrial sources such as insecticides, photographic solutions, and jewelry cleaner. It has been used as a poison in mass homicides and suicides. During World War II, the Nazis used cyanide as an agent of genocide in gas chambers. 
Cyanide poisoning may result from a variety of exposures including structural fires, industrial exposures, medical exposures such as sodium nitroprusside, and certain foods. In domestic countries, the most common cause of cyanide poisoning is domestic fires. Cyanide also is used in a number of industrial applications such as electroplating injury production, photography, plastics and rubber manufacturing, and pesticides. Sodium nitroprusside, a medication used to treat a hypertensive emergency, contains five cyanide groups per molecule. Toxic levels of cyanide may be present in patients who receive prolonged infusions of sodium nitroprusside.
There were 3165 human exposures to cyanide from 1993 to 2002 according to the Toxic Exposure Surveillance System. Of that number, only 2.5% were fatal. Fire is the most common source of cyanide exposure in industrialized countries such as the United States. Approximately 35% of all fire victims will have toxic levels of cyanide in their blood on presentation for medical treatment. According to National Poison Data System of a Poison Control Centers annual report, there were 247 reported cases of chemical exposures to cyanide in the United States in 2007, five of which were fatal.
Intravenous and inhalation of cyanide produce a more rapid onset of signs and symptoms than exposure via the oral or transdermal route. This is due to the first two routes providing fast diffusion into the bloodstream. The toxicity of cyanide is linked mainly to the cessation of aerobic cell metabolism. Cyanide reversibly binds to the ferric ions cytochrome oxidase three within the mitochondria. This effectively halts cellular respiration by blocking the reduction of oxygen to water.
Cyanide's main effect is that it inhibits oxidative phosphorylation, a process where oxygen is utilized for the production of essential cellular energy sources in the form of ATP. It does so by binding to the enzyme cytochrome C oxidase and blocks the mitochondrial transport chain. After that, cellular hypoxia and the depletion of ATP occur, leading to metabolic acidosis. The utilization of oxygen by the tissue occurs and is followed by the impairment of vital functions.
Cyanide absorbs quickly through the respiratory tract and mucous membranes as well as the gastrointestinal tract and skin. Signs and symptoms begin at blood cyanide concentrations of approximately 40 mol/L. In vivo, cyanide metabolism and neutralization involve a number of mechanisms. The most important of these is the detoxification of cyanide via rhodanese, an enzyme found abundantly in many tissues but in the liver and muscle particularly. Thiosulfate serves as a sulfur donor in the reaction catalyzed by rhodanese that converts cyanide to thiocyanate, a water-soluble molecule excreted in the urine.
The patient can present with symptoms as quickly as one minute after inhalation and within a few minutes of cyanide ingestion. If the hydrogen cyanide was inhaled, the victim might detect a bitter, almond odor, which is discernible by approximately 60% of the population. The clinical manifestations can be divided into early and late categories. Some early central nervous system findings are headache, dizziness, confusion, and mydriasis. These are due to tissue hypoxia, and seizures and coma can develop as it progresses to an altered level of consciousness. Early respiratory and cardiovascular findings include tachypnea and tachycardia, while late findings include apnea, hypotension, and cardiac arrhythmia. Hypotension and bradycardia are pathognomonic for cyanide poisoning. It is important to note that a patient's skin can be a normal or slightly ashen appearance despite tissue hypoxia. Patients with cyanide poisoning will not be cyanotic but will have a cherry red color due to excess oxygen in the bloodstream.
Labs that are pertinent to the initial evaluation in a patient with cyanide poisoning are complete blood count, electrolytes, urinalysis, urine tox screen, arterial blood gas, carboxyhemoglobin level (if in a fire), chest x-ray and EKG. A plasma lactate also may be obtained, and a level of greater than eight mmol/L is 94% sensitive and 70% specific for significant cyanide toxicity. All patients presenting from a structural fire are to be presumed to have cyanide toxicity. Also, consider obtaining acetaminophen and salicylate levels to rule out co-ingestions. An increased anion gap metabolic acidosis is expected in patients with cyanide poisoning. It is also advisable to get a carboxyhemoglobin level in patients where this is a concern such as fire or smoke inhalation victims.
Cyanide concentration levels may be obtained; however, the results are not available in time to be clinically useful. The results of direct testing are often unreliable because proper storage and prompt blood draws are needed. Given this fact, the clinician must rely on the presenting symptoms and the general clinical status of the patient.
Given the profound effects of cyanide toxicity, the provider must prepare to stabilize the patient's airway, breathing, and circulation. Of note, mouth-to-mouth resuscitation is contraindicated in cyanide poisoning because of risk to the provider of CPR.
Decontamination is a vital part in the management of a patient with cyanide exposure through topical and inhalation routes. They must be removed from the source and have their clothing removed and discarded appropriately. Gastrointestinal decontamination must be administered quickly. Although lab studies have demonstrated that activated charcoal binds poorly to cyanide, animal studies report decreased mortality when subjects were given activated charcoal. It is suggested that a single dose of activated charcoal of 50g in adults and 1 g/kg, up to max 50g in children be given.
Antidotes for cyanide poisoning must be given immediately if no contraindications are present.
Hydroxycobalamin is the antidote of choice for acute cyanide poisoning, especially if the patient has coexisting carbon monoxide poisoning. Other antidotes, which will be discussed later, impair oxygen carrying capacity and worsen cellular hypoxia and acidosis. The standard dose is 5 grams given intravenously (IV over 15 minutes, Be aware that this antidote turns urine dark red; this is not due to myoglobinuria.
A cyanide antidote kit may be used in place of hydroxycobalamin if it is not available. The kit that is currently available contains sodium nitrite and sodium thiosulfate. Sodium nitrite 300 mg ampule or 10 mg/kg given IV for 3 to 5 minutes in adults. The pediatric dose is 0.2 mL/kg and not exceed 10 mL in pediatric patients. The dose of sodium thiosulfate is one ampule or 12.5 grams in 50 mL, given intravenously for 30 minutes in adults. The dose for pediatric patients is 7 g/m2 and not to exceed 12.5 grams.
Hyperbaric oxygen treatment remains controversial due to inconsistent findings in the literature overall. Two animal studies did show some improvement in hyperbaric oxygen in addition to antidotal therapy.
The number one differential diagnosis is probably carbon monoxide inhalation. Patients with only carbon monoxide poisoning will improve when removed from the smoke-filled area and placed on 100% oxygen. Seizures are common in cyanide poisoning but are rare in carbon monoxide poisoning. Also of note is that carbon monoxide does not affect the pupils, but cyanide poisoning causes pupillary dilation.
Tricyclics antidepressants, isoniazid, organophosphates, and salicylates also are possible ingestions to consider when a patient presents with altered mental status, seizures, hypotension, and lactic acidosis.
Cyanide is one of the most rapidly lethal poisons known to man. Cyanide can lead to death in a few minutes to a few hours; therefore, rapid treatment is needed in these patients.
Because early treatment is so important in cyanide toxicity, the most obvious pitfall would be not making the diagnosis early in the course. Some complications that survivors of severe cyanide poisoning may encounter are Parkinson or other forms of neurological sequelae. The basal ganglia is particularly sensitive to cyanide toxicity. Chronic cyanide exposure can lead to vague symptoms such as a headache, abnormal taste, vomiting, chest pain, and anxiety.
The key to managing cyanide toxicity is patient education. Healthcare workers that include nurses, pharmacists, and physicians need to educate the public about the dangers of cyanide in the workplace. Cyanide can even be absorbed through the skin, hence people who work with cyanide-related chemicals must wear appropriate garments and protective inhalational devices. The public should also be educated on buying cyanide containing anticancer and anti-HIV treatments that are sold over the internet. The public should be asked to speak to their health care provider before purchasing such products. Finally, all patients exposed to cyanide should follow up with their healthcare provider to ensure that they have not developed any residual neuropsychiatric sequelae. In addition, patients treated with hydroxocobalamin should avoid sun exposure to prevent photosensitivity. (Level V)
The outcomes after cyanide poisoning depend on the concentration. Those with mild exposure and few symptoms usually have a good prognosis but those with severe exposure usually have a poor outcome. People who intentionally take large doses usually have a poor outcome. Patients who are removed from the exposure and treated immediately tend to have a good outcome. Following intravenous administration, cyanide can result in a fatality within seconds or minutes, compared to a few hours after oral ingestion. Even individuals who survive may have signs of anoxic encephalopathy. Anecdotal reports indicate that movement disorders and neuropsychiatric symptoms are not uncommon. (Level V)