Cyanide toxicity is generally considered to be a rare form of poisoning. However, cyanide exposure occurs relatively frequently in patients with smoke inhalation from residential or industrial fires.[1] In addition, intensive treatment with sodium nitroprusside or long-term consumption of cyanide-containing foods is a possible source of cyanide poisoning.[2, 3] Historically, cyanide has been used as a chemical warfare agent, and it could potentially be an agent for a terrorist attack.[4, 5]
Depending on its form, cyanide may cause toxicity through inhalation, ingestion, dermal absorption, or parenteral administration. Clinical manifestations vary widely, depending on the dose and route of exposure, and may range from minor upper airway irritation to cardiovascular collapse and death within minutes. (See Presentation.) In severe cases, rapid, aggressive therapy consisting of supportive care and antidote administration can be lifesaving. (See Treatment and Medication.)
Cyanide exists in gaseous, liquid, and solid forms. Hydrogen cyanide (HCN, also known as prussic acid) is a volatile liquid that boils at 25.6° C (78.1° F). Potassium and sodium cyanide salts are water soluble, whereas mercury, copper, gold, and silver cyanide salts are poorly water soluble.
In addition, a number of cyanide-containing compounds, known as cyanogens, may release cyanide during metabolism. These include, but are not limited to, cyanogen chloride and cyanogen bromide (gases with potent pulmonary irritant effects), nitriles (R-CN), and the vasodilator nitroprusside sodium, which may produce iatrogenic cyanide poisoning during prolonged or high-dose intravenous (IV) therapy (>10 mcg/kg/min). (See Etiology.)
Industry widely uses nitriles as solvents and in the manufacturing of plastics. Nitriles may release HCN during burning or when metabolized after absorption by the skin or gastrointestinal tract. A number of synthesized and natural compounds produce HCN when burned. These combustion gases likely contribute to the morbidity and mortality from smoke inhalation. Finally, long-term consumption of cyanide-containing foods, such as cassava root or apricot seeds,[3] may lead to cyanide poisoning.
HCN (North Atlantic Treaty Organization [NATO] designation AC) is one of two cyanide chemical warfare agents[6, 7, 8] ; the other is cyanogen chloride (NATO designation CK). Cyanide is a rapidly lethal agent when used in enclosed spaces where high concentrations can be achieved easily.[9, 10, 11, 12] In addition, because of the extensive use of cyanide in industry in the United States, this agent presents a credible threat for terrorist use.[7]
Cyanide was first used as a chemical weapon in the form of gaseous HCN in World War I. Starting in 1915, the French military used approximately 4000 tons of cyanide, without notable success. The failure of this measure was probably attributable to the high volatility of cyanide and the inability of the 1- to 2-lb munitions used to deliver the amounts of chemical required for biologic effects.[7, 8]
The introduction of cyanogen chloride by the French in 1916 made available a compound that, being both more toxic and less volatile, was a more effective chemical agent. Other alleged military uses of cyanide include Japanese attacks on China before and during World War II and Iraqi attacks on Kurds in the 1980s.
For related information, see the Disaster Preparedness and Aftermath Resource Center.[13, 14]
Cyanide exposure most often occurs via inhalation or ingestion, but liquid cyanide can be absorbed through the skin or eyes. Once absorbed, cyanide enters the blood stream and is distributed rapidly to all organs and tissues in the body.[15]
Inside cells, cyanide attaches itself to ubiquitous metalloenzymes, rendering them inactive. Its principal toxicity results from inactivation of cytochrome oxidase (at cytochrome a3), thus uncoupling mitochondrial oxidative phosphorylation and inhibiting cellular respiration, even in the presence of adequate oxygen stores. Cellular metabolism shifts from aerobic to anaerobic, with the consequent production of lactic acid. Consequently, the tissues with the highest oxygen requirements (brain and heart) are the most profoundly affected by acute cyanide poisoning.
The LCt50 (the concentration-time product capable of killing 50% of the exposed group) for hydrogen cyanide is 2500-5000 mg/min/m3. Vapor exposures in high concentrations (at or above the LCt50) typically can cause death in 6-8 minutes.[4] The lethal oral doses of HCN and cyanide salts are estimated to be 50 mg and 100-200 mg, respectively. For skin exposures, the LD50 (the dose capable of killing 50% of the exposed group) is estimated to be 100 mg/kg.
Cyanogen chloride is used in mining and metalworking, and thus may be involved in an industrial accident. By nature of its chlorine moiety, cyanogen chloride 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), this agent is rapidly acting and lethal, causing death within 6-8 minutes if inhaled at doses at or above its LCt50 of 11,000 mg/min/m3.
Defective cyanide metabolism due to rhodanese deficiency may explain development of Leber optic atrophy, leading to subacute blindness. Cyanide also may cause some of the adverse effects associated with chronic smoking, such as tobacco amblyopia.
Smoke inhalation, suicidal ingestion, and industrial exposures are the most frequent sources of cyanide poisoning. Treatment with sodium nitroprusside or long-term consumption of cyanide-containing foods is a possible source. Historically, cyanide has been used as a chemical warfare agent, and it could potentially be an agent for a terrorist attack.[4, 5]
Smoke inhalation during house or industrial fires is the major source of cyanide poisoning in the United States. Individuals with smoke inhalation from enclosed space fires who have soot in the mouth or nose, altered mental status, or hypotension may have significant cyanide poisoning (blood cyanide concentrations >40 mmol/L or approximately 1 mg/L).
Many compounds containing nitrogen and carbon may produce hydrogen cyanide (HCN) gas when burned. Some natural compounds (eg, wool, silk) produce HCN as a combustion product.[6, 16] Household plastics (eg, melamine in dishware, acrylonitrile in plastic cups), polyurethane foam in furniture cushions, and many other synthetic compounds may produce lethal concentrations of cyanide when burned under appropriate conditions of oxygen concentration and temperature.
Cyanide ingestion is an uncommon, but effective, means of suicide.[17] These cases typically involve health-care and laboratory workers who have access to the cyanide salts found in hospital and research laboratories.
Countless industrial sources of cyanides exist. Cyanides are used particularly in the metal trades, mining, jewelry manufacturing, dyeing, photography, and agriculture. Specific industrial processes involving cyanide include metal cleaning, reclaiming, or hardening; fumigation; electroplating; and photo processing.[5] In addition, industry uses cyanides in the manufacture of plastics, as reactive intermediates in chemical synthesis, and as solvents (in the form of nitriles).
Exposure to salts and cyanogens occasionally causes poisonings; however, a significant risk for multiple casualties occurs when these products come into contact with mineral acids because HCN gas is produced. A mass casualty incident may develop in an industrial accident in which cyanogen chloride comes in contact with water (eg, during fire-fighting). Containers of cyanogen chloride may rupture or explode if exposed to high heat or following prolonged storage.
The vasodilator nitroprusside sodium, when used in high doses or over a period of days, can produce toxic blood concentrations of cyanide. Patients with low thiosulfate reserves (eg, malnourished, postoperative) are at increased risk for developing symptoms, even with therapeutic dosing. Resultant confusion and combativeness initially may be mistaken as intensive care unit (ICU) syndrome (ie, sundowning). Problems may be avoided by coadministration of hydroxocobalamin or sodium thiosulfate.
Ingestion of cyanide-containing supplements is rare. Amygdalin (synthetic laetrile, also marketed as vitamin B-17), which contains cyanide, was postulated to have anticancer properties due to the action of cyanide on cancer cells. However, laetrile showed no anticancer activity in human clinical trials in the 1980s and is not available in the United States,[18] although it can be purchased on the Internet.[19]
Amygdalin can be found in the pits of many fruits, such as apricots and papayas; in raw nuts; and in plants such as lima beans, clover, and sorghum. Amygdalin can be hydrolyzed to hydrogen cyanide, and ingestion of large quantities of such foods may result in toxicity.[5]
Cyanide may be a major contributor to the morbidity and mortality observed in the approximately 5000-10,000 deaths from smoke inhalation occurring each year in the United States. Suicidal exposures are rarely reported to poison centers: intentional exposures accounted for 19 of the 187 cyanide poisoning cases reported to the American Association of Poison Control Centers in 2014.[20] However, a rapidly fatal suicide from cyanide salts in an adult patient might easily be mistaken for sudden death from myocardial infarction, pulmonary embolus, or ventricular dysrhythmia.
Suicide by cyanide poisoning occurs predominantly in males, as does industrial exposure. Leber optic atrophy has shown a very strong male predominance in European studies.
Deliberate ingestion of cyanide occurs mostly in adults. Smoke inhalation and chronic cyanide poisoning affect all ages.
The prognosis in cyanide toxicity is good for patients who have only minor symptoms that do not necessitate the administration of antidotes. The prognosis is reasonably good for patients with moderate symptoms if rapid supportive intervention and effective antidotal therapy are provided. Suicidal poisonings tend to have severe outcomes because large doses are often involved.
The prognosis in patients with cyanogen poisoning is better in those with low-level exposures with minor symptoms that resolve after they are removed from exposure. The prognosis is fair for patients with seizures or recent-onset apnea if antidotes can be administered rapidly. The prognosis is generally poor in patients who suffer cardiac arrest secondary to cyanide toxicity, even if antidotes are administered promptly.
According to the American Association of Poison Control Centers Toxic Exposure Surveillance System, 7 of the 202 cyanide exposure cases in 2012 were fatal.[20] Cyanide induces fatality in seconds to minutes following inhalation or intravenous injection, in minutes following ingestion of soluble salts, or minutes (hydrogen cyanide) to several hours (cyanogens) after skin absorption.
Individuals who survive cyanide poisoning are at risk for central nervous system dysfunction, such as anoxic encephalopathy. Acute and delayed neurologic manifestations (Parkinson-like syndrome, other movement disorders, neuropsychiatric sequelae) have been reported.
Educate patients using cyanide in their jobs about safe work practices, including the use of personal protective equipment. Certain cyanide compounds are well absorbed dermally; thus, gloves and other forms of skin protection should be worn. Moreover, cyanide compounds should be scrupulously isolated from exposure to acids.
Educate patients with cancer or human immunodeficiency virus (HIV) who might purchase anticancer supplements over the Internet about the possible risks from such medicines. Encourage them to discuss supplement use with their oncologist.
Patients who have been exposed to cyanide should be educated about potential neurologic sequelae and the importance of follow-up evaluation. Patients treated with hydroxocobalamin who develop skin erythema should be cautioned to avoid exposure to sunlight while the discoloration persists, due to possible photosensitivity. These patients may also develop red discoloration of their urine as an expected side effect that resolves without treatment.
For patient education information, see Personal Protective Equipment , theFirst Aid and Emergency Center and the Lung Disease and Respiratory Health Center, as well as Cyanide Poisoning and Smoke Inhalation.
Key historical features for suspected hydrogen cyanide (HCN) casualties include the following[5, 4] :
The delay between exposure and the onset of symptoms depends on the type of cyanide involved, the route of entry, and the dose. Rapidity of symptom onset, depending on the type of cyanide exposure, occurs in the following order (most rapid to least rapid): gas, soluble salt, insoluble salt, and cyanogens.
A history of recent depression in the patient with sudden collapse or altered mental status, metabolic acidosis, and tachyphylaxis in an intensive care unit patient who is receiving nitroprusside should evoke suspicion of the diagnosis.
Symptoms may include the following:
Symptoms after exposure to high vapor concentrations may include the following:
Symptoms after exposure to lower vapor concentrations or after ingestion or liquid exposure may include the following:
Patients exposed to cyanogen chloride experience severe eye and mucous membrane irritation.[21] Low-dose exposure results in rhinorrhea, bronchorrhea, and lacrimation. Inhalational exposure results in dyspnea, cough, and chest discomfort. Onset of symptoms after exposure to nitriles (acetonitrile and/or propionitrile) may be significantly delayed.
Physical findings of cyanide exposure are generally nonspecific, yet the onset of illness may be dramatic. Findings can include the following:
Neurologic symptoms may include the following:
Classically, the skin of a cyanide-poisoned patient is described as cherry red in color due to elevated venous oxygen content resulting from failure of tissues to extract oxygen. In addition, arterialization of the venous blood may also be noted during phlebotomy or examination of the retinal veins. Alternatively, patients may be cyanotic after prolonged respiratory failure and shock. Despite its name, cyanosis is not a prominent finding of cyanide poisoning. Finally, many patients with cyanide poisoning have normal-appearing skin.
The workup in patients with cyanide exposure may include the studies discussed below.
Cyanide toxicity is characterized by a normal arterial oxygen tension and an abnormally high venous oxygen tension, resulting in a decreased arteriovenous oxygen difference (< 10%). A high-anion-gap metabolic acidosis is a hallmark of significant cyanide toxicity.[9, 22] Apnea may result in combined metabolic and respiratory acidosis.
Elevation in the blood lactate level is a sensitive marker for cyanide toxicity. A plasma lactate concentration of greater than 10 mmol/L in smoke inhalation or greater than 6 mmol/L after reported or strongly suspected pure cyanide poisoning suggests significant cyanide exposure.[23]
Cyanide blood concentrations are not generally available in time to aid in the treatment of acute poisoning, but may provide subsequent confirmation. In cyanogen exposures, these tests provide documentation for therapeutic use, which may last several days.
The preferred test is a red blood cell cyanide concentration. With this method, mild toxicity is observed at concentrations of 0.5-1.0 μg/mL. Concentrations of 2.5 μg/mL and higher are associated with coma, seizures, and death. Blood cyanide concentrations may artificially increase after sodium nitrite (antidote) administration, because of in vitro release of cyanide from cyanomethemoglobin during the analytical procedure by strong acid used in analysis.
Carboxyhemoglobin (HbCO) level (by co-oximetry) or blood carbon monoxide concentration (by infrared spectroscopy) may be obtained in patients with smoke inhalation to rule out concurrent exposure. HbCO measurements may be artificially elevated in blood samples drawn after hydroxocobalamin administration.[24]
A methemoglobin level is especially important in cyanotic patients. The presence of methemoglobin suggests that little or no free cyanide is available for binding, because methemoglobin vigorously binds cyanide to form cyanomethemoglobin (which is not measured as methemoglobin).
Methemoglobin concentrations provide a guide for continued therapy after the use of methemoglobin-inducing antidotes, such as sodium nitrite. Elevated levels of methemoglobin (>10%) indicate that further nitrite therapy is not indicated and, in fact, may be dangerous.
On ECG, nonspecific findings predominate. Abnormalities may include the following[25] :
In some cases, shortening of the ST segment with eventual fusion of the T wave into the QRS complex has been observed.
No imaging studies are indicated acutely for cyanide exposure, but magnetic resonance imaging (MRI) may be useful during the evaluation of postexposure neurologic sequelae.
Fluorescein staining and slit-lamp examination of the eyes may be necessary following decontamination to assess corneal integrity.
Administer a cyanide antidote if the diagnosis of cyanide toxicity is strongly suspected, without waiting for laboratory confirmation. Available antidotes are hydroxocobalamin (Cyanokit) and sodium thiosulfate and sodium nitrite (Nithiodote). Both are given intravenously.
Patients who present with more than minimal symptoms that resolve without treatment should be admitted for observation and supportive care. In patients with acute poisoning from hydrogen cyanide (HCN) gas or soluble salts, the principal acute care concerns are hemodynamic instability and cerebral edema. The continuous cardiac monitoring, respiratory and cardiovascular support, and frequent neurologic evaluation these patients require is generally best provided in an intensive care unit.
Conversely, acute poisoning from cyanogens (nitriles) or poorly soluble salts may not manifest or become life-threatening for several hours after exposure. These patients require a 24-hour observation period.[26, 27]
Oxygenation should be optimized and continuous cardiac monitoring provided. Depending on the severity of symptoms, endotracheal intubation may be necessary to optimize oxygen delivery and protect the airway. Serum lactate concentrations, chemistries, and arterial or venous blood gases should be monitored.
Patients should be reevaluated 7-10 days after discharge from the hospital.[28] Delayed onset of Parkinson-like syndrome or neuropsychiatric sequelae may be noted on followup.
Fetal demise is possible in cyanide poisoning. Aggressive support and antidotal treatment of the mother is paramount. An obstetric evaluation following stabilization of the mother is essential. Therapeutic abortion may be indicated in the presence of fetal demise.
Use of personal protective equipment is essential at many cyanide exposure scenes. Respiratory protection against hydrogen cyanide gas may be needed at fires and industrial accidents. Certain cyanide compounds can be absorbed dermally; emergency services personnel should wear gloves and other forms of skin protection.
Appropriate prehospital measures may include the following[7, 8] :
Aggressive airway management with delivery of 100% oxygen can be lifesaving. (Although theoretically useless, supportive care with administration of oxygen alone has proven effective in a number of poisonings.) It can also treat concomitant carbon monoxide exposure, pending measurement of blood levels.
Administer cyanide antidotes as soon as possible.[29, 26, 27] While not carried by all emergency medical technicians, some first responders do have protocols to administer hydroxocobalamin in the field. As a temporizing measure, amyl nitrite ampules can be crushed and their contents poured onto a gauze pad and placed in front of the patient's mouth, if the patient is breathing spontaneously, or ventilated into an apneic patient using a bag-valve-mask.
Initial emergency department care for patients with cyanide exposure is identical to that provided in the prehospital phase. Provide supportive care, including the following:
Decontaminate the patient with removal of clothing/skin flushing and/or activated charcoal (1g/kg), as appropriate. Activated charcoal should be given after oral exposure in alert patients who are able to protect the airway or after endotracheal intubation in unconscious patients. In recent ingestions, activated charcoal may be preceded by gastric lavage. The gastric aspirate may cause secondary contamination and should be viewed as hazardous.
Administer hydroxocobalamin or sodium thiosulfate and sodium nitrite if the diagnosis is strongly suspected. Do not wait for laboratory confirmation.
Antidotes to cyanide include hydroxocobalamin and sodium nitrite and sodium thiosulfate. Sodium thiosulfate may be given in combination with sodium nitrite or hydroxocobalamin, or may be given alone. These agents are administered intravenously.
Hydroxocobalamin, which is considered the drug of choice in continental Europe and Australia, is approved by the US Food and Drug Administration (FDA) for treating known or suspected cyanide poisoning.[30, 31] Coadministration of sodium thiosulfate (through a separate line or sequentially) has been suggested to have a synergistic effect on detoxification.
Hydroxocobalamin combines with cyanide to form cyanocobalamin (vitamin B-12), which is renally cleared.[32] Alternatively, cyanocobalamin may dissociate from cyanide at a slow enough rate to allow for cyanide detoxification by the mitochondrial enzyme rhodanese.
A review by Hall et al notes that hydroxocobalamin has not been associated with clinically significant toxicity in antidotal doses compared with other cyanide antidotes. Hydroxocobalamin has a rapid onset of action, neutralizes cyanide without interfering with cellular oxygen use, is conducive to prehospital use due to its tolerability and safety profiles, and is safe for use in patients with smoke inhalation.[33]
Adverse effects of hydroxocobalamin administration include transient hypertension (a benefit in hypotensive patients), reddish brown skin, mucous membrane and urine discoloration, and rare anaphylaxis and anaphylactoid reactions. Because of its bright red color, it also interferes with co-oximetry (about a 5% increase in carboxyhemoglobin levels) and blood chemistry testing (bilirubin, creatinine kinase and possibly liver enzymes, creatinine, phosphorus, glucose, magnesium, and iron levels).[34] It can also interfere with hemodialysis.[35]
Certain medications should not be administered simultaneously or through the same line as hydroxocobalamin. These include diazepam, dopamine, dobutamine, and sodium thiosulfate.
Sodium nitrite and sodium thiosulfate are often used in combination and are currently considered second-line therapy after hydroxocobalamin. Sodium nitrite is rapidly effective but can cause life-threatening toxicity, whereas sodium thiosulfate has a somewhat delayed effect but is far safer.
Sodium nitrite induces methemoglobin in red blood cells, which combines with cyanide, thus releasing cytochrome oxidase enzyme. Sodium thiosulfate donates a sulfur atom necessary for the transformation of cyanide to thiocyanate by rhodanese, thus increasing the activity of the endogenous detoxification system. The thiocyanate is then renally excreted.
Sodium nitrite should not be used in patients with smoke inhalation unless their carboxyhemoglobin concentration is very low (< 10%). The induction of methemoglobinemia by sodium nitrite compounds the effect of any existing carboxyhemoglobinemia, significantly reduces the oxygen-carrying capacity of blood. In addition, vasodilation from sodium nitrite may result in significant hypotension and cardiovascular collapse.[29]
Appropriate dosing of sodium nitrite has not been established in children. Consequently, these patients are at increased risk for excessive methemoglobinemia, hypotension, or both.
Optimize oxygenation. Monitor disease resolution by clinical criteria, serial plasma lactate concentrations, and arterial and venous blood gases. Perform serial electrocardiograms (ECGs) for patients with cardiac dysrhythmias or complaints of chest pain. Monitor for delayed onset of pulmonary edema in those presenting with evidence of respiratory irritation. Discharge the patient when neurologic status and cardiovascular status have normalized and acidosis and other metabolic abnormalities have resolved.
Avoid transfer of patients with acute cyanide toxicity. However, transfer the patient if antidotes and intensive care are unavailable and if rapid, appropriate medical transport can be assured. Ideally, transfer patients to a regional toxicology treatment center.
Provide medical stabilization (eg, airway, hemodynamic parameters) before transfer. Transfer with an advanced cardiac life support (ACLS) level of service under continuous cardiac monitoring with supplemental oxygen and intravenous access.
Smoke alarms significantly reduce the incidence of serious smoke inhalation injury. Workplaces using cyanides should have engineering controls in place to avoid inadvertent exposures. Workers should be provided with personal protective equipment and training; they should be instructed to avoid contact between cyanide salts and mineral acids or other compounds with low pH.
Patients receiving sodium nitroprusside at high doses or for more than 5 days should have monitoring of blood cyanide or thiocyanate concentrations. Alternatively, these patients can be treated prophylactically with sodium thiosulfate or hydroxocobalamin to reduce the risk of iatrogenic cyanide poisoning.
Consultation with a medical toxicologist or a poison control center is recommended. They should be contacted immediately upon consideration of cyanide as a diagnosis, given the critical nature of these cases.[7] They can provide recommendations regarding the most effective available antidotal therapy, as well as insight into potential sources of poisoning (eg, industrial) that may place others at risk. Online resources may also be consulted (see the chart below).
Chemical terrorism agents and syndromes: signs and symptoms (PDF) (Copyright University of North Carolina at Chapel Hill)
Consult with law enforcement authorities and the Federal Bureau of Investigation (FBI) in any suspected terrorist incident.
Oxygen is the initial agent used in suspected or confirmed cyanide poisoning. Sodium bicarbonate is used in patients with severe poisoning that has produced marked lactic acidosis. Epinephrine is used to support cerebral and coronary perfusion in low-flow states.
Antidotal therapy is indicated for any patient in whom the diagnosis of cyanide toxicity is considered on clinical grounds, even before laboratory confirmation. Activated charcoal can be used in patients presenting after ingestion of cyanide salts or organic cyanides.
Anticonvulsants are used as indicated. Lorazepam is the drug of choice; midazolam and phenobarbital are second-line agents.
Cyanide antidotes are the key medications for hydrogen cyanide (HCN) poisoning. Hydroxocobalamin (HCO, vitamin B-12) is the first-line therapy for cyanide toxicity. It functions by binding cyanide to its cobalt ion to form cyanocobalamin, which is essentially nontoxic and is cleared renally.[36, 33] HCO can be combined with sodium thiosulfate for accelerated detoxification. Amyl nitrite is an alternative temporizing therapy; it may be useful in the absence of intravenous (IV) access (eg, in industrial settings).
Sodium thiosulfate enhances the conversion of cyanide to thiocyanate , which is renally excreted. Thiosulfate has a somewhat delayed effect and thus is typically used with sodium nitrite for faster antidote action. Sodium nitrite must be used with caution because it may result in significant hypotension and cardiovascular collapse, in addition to generating dangerous levels of methemoglobin. However, in cases of smoke inhalation in which cyanide toxicity is suspected, administration of sodium thiosulfate is safe.
Clinical Context: Hydroxocobalamin contains cobalt ion, which is able to bind to cyanide with greater affinity than cytochrome oxidase to form nontoxic cyanocobalamin (vitamin B-12), which is excreted in urine. Hydroxocobalamin has few adverse effects and is tolerated by critically ill patients. It is well tolerated by patients with concomitant carbon monoxide poisoning, because unlike sodium nitrite it has no effect on the oxygen-carrying capacity of hemoglobin.
Hydroxocobalamin may be used in combination with sodium thiosulfate for treatment of acute cyanide toxicity. Low-dose hydroxocobalamin in combination with sodium thiosulfate has been used successfully to prevent cyanide toxicity in patients receiving prolonged sodium nitroprusside infusions.
The disadvantages of hydroxocobalamin are that a large dose is required for antidotal efficacy and that it is available in the United States only in very dilute solutions. It can cause transient hypertension, allergic reactions (rarely including anaphylaxis and angioedema), and a reddish discoloration of body fluids and urine.
Clinical Context: Sodium nitrite induces methemoglobin formation and vasodilation. Sodium thiosulfate has a slower mechanism of action. It donates sulfur, which is used as a substrate by rhodanese and other sulfur transferases for detoxification of cyanide to thiocyanate. In patients with concomitant carbon monoxide poisoning, for whom sodium nitrite is contraindicated, sodium thiosulfate can be used alone; sodium thiosulfate can also be administered with hydroxocobalamin in severe cases.
The recommended dose assumes a patient hemoglobin level of 12 mg/dL; dosage adjustment may be necessary in patients with anemia. Half the original dose may be repeated in 1 hour if the patient continues to exhibit signs of cyanide toxicity.
Clinical Context: The nitrite ions in amyl nitrite react with hemoglobin to form methemoglobin, which unites with cyanide to form cyanomethemoglobin. Amyl nitrite rushed and contents poured onto a gauze and placed in front of patient's mouth pearls can be crushed and inhaled by a spontaneously breathing patient or ventilated into an apneic patient using a bag-valve-mask device; this is a temporizing measure until IV access can be established.
The effect of an ampule lasts approximately 3 minutes; separate administration by at least 30 seconds to allow patient to oxygenate. Due to the volatile nature of this compound, rescuers should ensure that they themselves have an adequate fresh air supply and can maintain a sufficient distance from the amyl nitrite source.
Clinical Context: Activated charcoal binds cyanide poorly; 1 g of charcoal adsorbs only 35 mg of cyanide. Nonetheless, a 1-g/kg dose of charcoal could potentially bind a lethal dose of cyanide and has a low risk profile. Consequently, charcoal should be administered as soon as possible following oral ingestion of cyanide salts or organic cyanides.
Clinical Context: Sodium bicarbonate may be required in large doses for alkalization.
Cyanide is a cellular toxin that binds to cytochrome oxidase, inhibiting cellular respiration. Antidotes either directly counteract cyanide's toxicity on the electron transport chain or help the body eliminate the cyanide molecule. Administration of antidotes is critical for life-threatening intoxication.
Gastrointestinal (GI) decontamination with oral activated charcoal is selectively used in the emergency treatment of poisoning caused by some drugs and chemicals. The network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Consider decontamination with activated charcoal in any patient who presents within 4 hours after the ingestion.
Alkalinizing agents are used in severe poisoning, which causes marked lactic acidosis.
Clinical Context: Lorazepam is the drug of choice for cyanide-induced seizures. It is a sedative hypnotic with a rapid onset of effect and a relatively long half-life. By increasing the action of GABA, a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the central nervous system, including the limbic and reticular formation.
Clinical Context: Pentobarbital is a short-acting barbiturate that interferes with transmission of impulses from the thalamus to the cortex. It has sedative, hypnotic, and anticonvulsant properties. It is a second-line drug for treatment of drug-induced seizures.
Cyanide inhibits brain glutamate decarboxylase, which causes a decrease in the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and contributes to convulsions. Therefore, anticonvulsant drugs such as benzodiazepines or barbiturates, which act at the GABA receptor complex, can help control seizures.
Clinical Context: Epinephrine is the drug of choice for treating anaphylactoid reactions. It has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Its beta-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.
These agents augment coronary and cerebral blood flow during the low-flow states associated with cyanide poisoning.