eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Cyanide

Inna Leybell, MD, Staff Physician, Department of Emergency Medicine, Bellevue Hospital, New York University Hospital
Robert S Hoffman, MD, FAACT, FACMT, Associate Professor, Departments of Emergency Medicine and Medicine, Clinical Pharmacology, New York University School of Medicine, Consulting Staff, Department of Emergency Services, Bellevue and New York University Hospital; Stephen W Borron, MD, MS, FACEP, FACMT, Clinical Professor of Emergency Medicine, Surgery, Consultant to the South Texas Poison Center, University of Texas Health Science Center at San Antonio; President and Chief Medical Officer of International Toxicology Consultants

Updated: Dec 17, 2008

Introduction

Background

Cyanide is generally considered to be a rare source of poisoning; however, cyanide exposure occurs relatively frequently in patients with smoke inhalation from residential or industrial fires. Cyanide poisoning also may occur in industry, particularly in the metal trades, mining, electroplating, jewelry manufacturing, and x-ray film recovery. It is also encountered in fumigation of ships, warehouses, and other structures. Cyanides are also used as suicidal agents, particularly among healthcare and laboratory workers, and they can potentially be used in a terrorist attack.  

Numerous forms of cyanide exist, including gaseous hydrogen cyanide (HCN), water-soluble potassium and sodium cyanide salts, and poorly water-soluble mercury, copper, gold, and silver cyanide salts. 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 sodium nitroprusside, which may produce iatrogenic cyanide poisoning during prolonged or high-dose intravenous therapy (>10 mcg/kg/min).

Industry widely uses nitriles as solvents and in the manufacturing of plastics. Nitriles may release HCN during burning or when metabolized following absorption by the skin or gastrointestinal tract. A number of synthesized (eg, polyacrylonitrile, polyurethane, polyamide, urea-formaldehyde, melamine) and natural (eg, wool, silk) compounds produce HCN when burned. These combustion gases likely contribute to the morbidity and mortality from smoke inhalation. 

Finally, chronic consumption of cyanide-containing foods, such as cassava, may lead to cyanide poisoning.

Overall, depending on its form, cyanide may cause toxicity through parenteral administration, inhalation, ingestion, or dermal absorption.

Pathophysiology

Cyanide affects virtually all body tissues, attaching itself to ubiquitous metalloenzymes and 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.

Chronic consumption of cyanide-containing foods eventually can result in ataxia and optic neuropathy. 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.

Frequency

United States

Cyanide may be a major contributor to the morbidity and mortality observed in approximately 5,000-10,000 deaths from smoke inhalation occurring each year in the United States. Suicidal exposures are rarely reported to poison centers; in 2004, 32 of 257 were intentional exposures reported to the American Association of Poison Control Centers.¹ However, a rapidly fatal suicide from cyanide salts in an adult patient easily might be attributed to sudden death from myocardial infarction, pulmonary embolus, or ventricular dysrhythmia.

International

Studies in France, Sweden, and Scotland, as well as the United States, document smoke inhalation as an important source of cyanide poisoning. 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).

Mortality/Morbidity

According to the American Association of Poison Control Centers Toxic Exposure Surveillance System, in 2005, 6 fatalities occurred out of 214 total cyanide exposures.¹

• 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 (eg, anoxic encephalopathy, Parkinsonlike syndrome).
• Rapid aggressive therapy, consisting of supportive care and antidote administration, is lifesaving.

Sex

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.

Age

Deliberate ingestion of cyanide occurs mostly in adults. Smoke inhalation and chronic cyanide poisoning affect all ages. 

Clinical

History

The delay between exposure and onset of symptoms depends on type of cyanide involved, route of entry, and 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.

Multiple casualties may present after a fire or hazardous materials incident involving cyanides. In some cases, the individuals involved may be experiencing collective hysteria. If physical findings are absent, cyanide poisoning is unlikely. If lactic acidosis is not present, cyanide poisoning has not occurred. Provide supportive care (oxygen) to all individuals presenting because of the event until absence of cyanide poisoning can be verified.

A history of recent depression in the patient with sudden collapse or altered mental status, acidosis, and tachyphylaxis in the ICU patient on nitroprusside should evoke suspicion of the diagnosis.

• General weakness, malaise, and collapse
• Neurologic symptoms (reflect progressive hypoxia)
  • Headache, vertigo, dizziness
  • Giddiness, inebriation, confusion
  • Generalized seizures
  • Coma
• Gastrointestinal symptoms - Abdominal pain, nausea, vomiting
• Cardiopulmonary symptoms
  • Shortness of breath, possibly associated with chest pain
  • Apnea

Physical

Physical findings of cyanide exposure are generally nonspecific, yet the onset of illness may be dramatic.

• Vital signs are variable.
  • Initial bradycardia and hypertension may rapidly give way to hypotension with reflex tachycardia, with resulting final bradycardia and hypotension.
  • Tachypnea may generally precede apnea.
  • Pulse oximetry may be high and falsely reassuring. (Oxygen is present in blood as oxyhemoglobin but cannot be effectively used in oxidative phosphorylation.)
• General: Cherry-red skin color (reflecting absent tissue oxygen extraction) may be observed.
• Head, ears, eyes, nose, and throat (HEENT)
  • Soot in the mouth and nose after smoke inhalation, particularly if altered mental status and/or hypotension are present, suggests the possibility of cyanide poisoning.
  • Mydriasis
  • Bright red retinal arteries and veins (due to absent tissue oxygen extraction)
  • The smell of bitter almonds on the breath suggests exposure (cannot be detected by 60% of the population).
• Cardiopulmonary
  • Possible cardiogenic pulmonary edema
  • Aspiration can occur with coma.
• Neurologic
  • Confusion, drunken behavior, ataxia
  • Mydriasis
  • Generalized convulsions
  • Coma

Causes

Smoke inhalation, suicidal ingestion, and industrial exposures are the most frequent sources of cyanide poisoning.

• Smoke inhalation
  • Many compounds containing nitrogen and carbon may produce hydrogen cyanide gas when burned. Some natural compounds (eg, wool, silk) produce HCN as a combustion product.
  • 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.
• Intentional poisoning
  • Cyanide ingestion is an uncommon but efficacious means of suicide, often involving cyanide salts found in hospital and research laboratories.
  • Not surprisingly, certain occupations, such as healthcare and laboratory workers, are at risk for suicidal ingestion of cyanides.
• Industrial exposure (Countless industrial sources of cyanides exist.)
  • Cyanides serve an extremely important role in the metal plating and recovery industries.
  • Industry utilizes 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 hydrogen cyanide gas is produced.
  • Water contact with the soluble salts (eg, potassium, sodium cyanide) also may liberate HCN.
• Iatrogenic exposure
  • Sodium nitroprusside 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 ICU syndrome (ie, sundowning).
  • Problems may be avoided by coadministration of hydroxocobalamin or sodium thiosulfate.
• Ingestion of cyanide-containing supplements (rare)
  • Amygdalin (synthetic laetrile, also marketed as vitamin B-17) contains cyanide and can be found in the pits of many fruits such as apricots and papayas, in raw nuts, and in other plants (lima beans, clover, and sorghum).
  • The substance was thought to have anticancer properties due to the action of cyanide on cancer cells.
  • Laetrile has shown no anticancer activity in human clinical trials in the 1980s and is not available in the United States,² but it can be purchased on the Internet.

Differential Diagnoses

Other Problems to Be Considered

Strychnine poisoning
Methanol toxicity
Azide toxicity

Workup

Laboratory Studies

• Arterial and venous blood gases
  • Metabolic acidosis, often severe, combined with reduced arterial-venous oxygen saturation difference (<10%) suggests diagnosis.
  • Apnea may result in combined metabolic and respiratory acidosis.
• Blood lactate level
  • A plasma lactate concentration 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.
• Red blood cell and plasma cyanide concentration
  • Cyanide blood concentrations are not generally available in time to aid in the treatment of acute poisoning.
  • In cyanogen exposures, these tests provide documentation for therapeutic use, which may last several days.
  • Blood cyanide concentrations may artificially increase after sodium nitrite administration because of in vitro release of cyanide from cyanomethemoglobin during the analytical procedure by strong acid used in analysis.
• Carboxyhemoglobin (HbCO) or blood carbon monoxide concentration (by infrared spectroscopy) may be obtained in patients with smoke inhalation to rule out concurrent exposure.
• Blood concentrations of methanol, ethylene glycol, iron, ketones, and salicylates may be useful in evaluation of unexplained metabolic acidosis. Pending results should not delay the treatment if cyanide exposure is suspected.
• Methemoglobin concentrations provide a guide for continued therapy after use of methemoglobin-inducing antidotes such as sodium nitrite.
  • Presence of methemoglobin suggests little or no free cyanide for binding because methemoglobin vigorously binds cyanide to form cyanomethemoglobin (not measured as methemoglobin).
  • Elevated levels of methemoglobin (>10%) indicate that further nitrite therapy is not indicated and, in fact, may be dangerous.

Imaging Studies

• No imaging studies are indicated acutely.
• MRI may be useful during evaluation of postexposure neurologic sequelae.

Other Tests

• ECG may show nonspecific changes.
  • Atrioventricular (AV) blocks
  • Supraventricular or ventricular arrhythmias
  • Ischemic ECG changes and eventual asystole

Treatment

Prehospital Care

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 CO exposure pending the levels.

• Intubate the patient if the patient is unconscious or the airway cannot be protected.
• Institute cardiac monitoring and an intravenous line; administer fluids and vasopressors for hypotension.
• Administer sodium bicarbonate if the patient is unconscious or hemodynamically unstable and acidotic (elevated lactate levels).
• Administer cyanide antidotes in the prehospital setting if the diagnosis is relatively certain. Such treatment generally should involve online medical control.
• Anticonvulsants may be needed for generalized seizures.

Emergency Department Care

Initial ED care is identical to that provided in the prehospital phase.

• Provide supportive care.
  • Airway control, ventilation, 100% oxygen delivery
  • Crystalloids and vasopressors as needed for hypotension
  • Sodium bicarbonate titrated according to ABG and serum bicarbonate level
• Decontaminate the patient with removal of clothing/skin flushing and/or activated charcoal (1 g/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. Remember to protect the healthcare provider from potential contamination.
• Administer Cyanide Antidote Kit (CAK) or hydroxocobalamin (Cyanokit) if the diagnosis is strongly suspected, without waiting for laboratory confirmation.
  • Cyanide Antidote Kit contains amyl nitrite pearls, sodium nitrite, and sodium thiosulfate.
    • Amyl and sodium nitrites induce methemoglobin in red blood cells, which combines with cyanide, thus releasing cytochrome oxidase enzyme. Inhaling crushed amyl nitrite pearls is a temporizing measure before intravenous administration of sodium nitrite.
    • 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.
    • Avoid the sodium nitrite portion of the cyanide kit in patients with smoke inhalation unless carboxyhemoglobin concentration is very low (<10%). The induction of methemoglobinemia from the nitrites in addition to present carboxyhemoglobinemia significantly reduces the oxygen-carrying capacity of blood.
    • Vasodilatation leading to hypotension is another adverse effect of CAK.
    • Appropriate dosing of sodium nitrite has not been established in children, who may develop excessive methemoglobinemia and/or hypotension. 
  • Hydroxocobalamin (Cyanokit), which has been routinely used in Europe, was recently approved by the US Food and Drug Administration (FDA) for treating known or suspected cyanide poisoning.
    • Hydroxocobalamin combines with cyanide to form cyanocobalamin (vitamin B-12), which is renally cleared.
    • Coadministration of sodium thiosulfate (through a separate line or sequentially) has been suggested to have a synergic effect on detoxification.
    • 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. It also interferes with co-oximetry and blood chemistry (liver enzymes, bilirubin, creatinine, creatine kinase, phosphorus, glucose, magnesium, and iron level) testing due to its bright red color.
    • Certain medications should not be administered simultaneously or through the same line as hydroxocobalamin. These include diazepam, dopamine, dobutamine, and sodium thiosulfate. 

Consultations

Consult a medical toxicologist for confirming the diagnosis, for recommendations regarding the most effective available antidotal therapy, and for insight as to potential sources of poisoning (eg, industrial) that may place others at risk.

Medication

Provide oxygen as the initial agent in suspected or confirmed cyanide poisoning. Administer sodium bicarbonate in severe poisoning because of marked lactic acidosis. Decontaminate as appropriate. Upon consideration of cyanide toxicity diagnosis, immediately administer antidotal therapy based on clinical criteria, even if laboratory confirmation of cyanide poisoning has not been received. Administer anticonvulsants as indicated.

Antidote, Cyanide

Cyanide is a cellular toxin that binds to cytochrome oxidase inhibiting cellular respiration. Administer antidotes to accelerate reversal of this activity.

Sodium nitrite

DOC in the United States. Induces methemoglobin formation and vasodilation.

Dosing

Adult

10 mL of 3% solution (300 mg) slow IV push over 2-5 min

Pediatric

Initial dose: 0.33 mL/kg (10 mg/kg) immediately, and repeat 0.165 mL/kg (5 mg/kg) in 30 min, to a maximum of 10 mL (300 mg) total
Lower doses should be used if child has hemoglobin level less than 12 g/100 mL

Interactions

Methylene blue will counteract methemoglobin formation

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May produce hypotension with large dose or rapid IV; high methemoglobin levels may exacerbate ischemia in patients with poor underlying cardiopulmonary reserve as oxygen-carrying capacity decreases; in severe anemia, adjust dose of sodium nitrite as outlined in package insert; measure methemoglobin levels 30 min after administration
Using adult dose in children can cause fatal hemoglobinemia and profound hypotension

Sodium thiosulfate (Tinver)

Second-line therapy because of slower mechanism of action. Regenerates sulfur-dependent rhodanese activity. Coadminister with or after sodium nitrite or hydroxocobalamin. Useful adjunct in prolonged (cyanogen) poisonings.

Dosing

Adult

12.5 g (50 mL) IV at 3-5 mL/min; may repeat at one-half initial dose after 1 h if symptoms persist

Pediatric

412.5 mg/kg IV (1.65 mL/kg) at 3-5 mL/min

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Rapid IV infusion may cause transient hypotension and ECG changes; caution in asthma.

Hydroxocobalamin (Vitamin B12, Cyanokit)

Contains cobalt ion, which is able to bind to cyanide with greater affinity than the cytochrome oxidase to form cyanocobalamin (nontoxic) and excreted in urine. Has few adverse effects and is tolerated by critically ill patients and well tolerated by patients with concomitant carbon monoxide poisoning (no effect on the oxygen carrying capacity of hemoglobin). In France, it commonly is used in combination with sodium thiosulfate. Low-dose hydroxocobalamin in combination with sodium thiosulfate has been used successfully to prevent cyanide toxicity due to prolonged sodium nitroprusside infusions.

Dosing

Adult

70 mg/kg IV over 15 min or 5 g IV over 15 min (faster if the patient is in cardiac arrest); may repeat dose once; when repeated, infusion should be over 15 min to 2 h; continuous IV infusion of 25 mg/h has been suggested for prophylaxis against sodium nitroprusside-induced cyanide toxicity

Pediatric

70 mg/kg IV over 15 min (non-US use)

Interactions

None reported

Contraindications

Documented hypersensitivity; hereditary optic nerve atrophy

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause transient red discoloration of plasma, urine, and mucous membranes; avoid use in premature infants; perform intradermal test dose for hypersensitivity

Amyl nitrite ampules (Isoamyl Nitrate)

Alternative temporizing therapy; may be useful in absence of IV access (eg, industrial settings).

Dosing

Adult

One ampule crushed and inhaled q30s until IV access is available for administration of sodium nitrite

Pediatric

Not established

Interactions

Coadministration with alcohol may cause severe hypotension and cardiovascular collapse; with calcium channel blockers, may produce symptomatic orthostatic hypotension; aspirin may increase nitrate serum concentrations

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

X - Contraindicated; benefit does not outweigh risk

Precautions

Caution in coronary artery disease and low systolic blood pressure

Anticonvulsants

Repeated or prolonged generalized seizures (status epilepticus) indicate anticonvulsant therapy.

Lorazepam (Ativan)

DOC; sedative hypnotic with short onset of effects and relatively long half-life.
By increasing the action of GABA, a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.
Excellent when the patient needs to be sedated for longer than 24 h. Commonly used prophylactically to prevent delirium tremens.

Dosing

Adult

2 mg IV over 2 min or IM; may repeat q10min until desired effect or total of 8 mg administered

Pediatric

0.05-0.1 mg/kg IV over 2-5 min; may be administered IM if IV access unavailable; may repeat at one-half initial dose after 10-15 min

Interactions

Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs

Contraindications

Documented hypersensitivity; preexisting CNS depression; hypotension; narrow-angle glaucoma

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease
Patient may experience transient respiratory depression requiring ventilatory support

Midazolam (Versed)

Used as alternative in termination of refractory status epilepticus. Because water soluble, takes approximately 3 times longer than diazepam to peak EEG effects; thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. Has twice the affinity for benzodiazepine receptors than diazepam. May be administered IM if unable to obtain IV access.

Dosing

Adult

0.01-0.05 mg/kg (usually 0.5-4 mg, up to 10 mg) IV administered slowly over several min; may repeat q10-15min prn

Pediatric

<32 weeks: 0.5 mcg/kg/min IV infusion
>32 weeks: 1 mcg/kg/min IV infusion
Children: 0.05-0.2 mg/kg IV over 2-3 min, followed by 1-2 mcg/kg/min continuous infusion
Status epilepticus (refractory to standard therapy), >2 months and children: 0.15 mg/kg followed by continuous infusion of 1 mcg/kg/min, titrating dose upward q5min until seizures controlled

Interactions

Sedative effects may be antagonized by theophyllines; narcotics, cimetidine, ethanol, and erythromycin may accentuate sedative effects because of decreased clearance; reduce dose of thiopental by 15% when using together

Contraindications

Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (diluent)

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in congestive heart failure, pulmonary disease, renal impairment, hepatic failure, neuromuscular disease, hypotension, and patients >60 y; monitor for respiratory depression with high or repeated doses; consider lower dosages in patients with organic brain syndrome and patients who may have inhibition of benzodiazepine metabolism and clearance (eg, using nicotine, taking cimetidine)
Patient may experience transient respiratory depression requiring ventilatory support

Phenobarbital sodium (Barbita, Luminal, Solfoton)

Second-line after benzodiazepines. Interferes with transmission of impulses from thalamus to cortex of brain. Used as a sedative.

Dosing

Adult

10-20 mg/kg IV over 20 min

Pediatric

10-20 mg/kg IV over 20 min

Interactions

May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects and fatality; chloramphenicol, valproic acid, and MAOIs may increase phenobarbital toxicity; rifampin may decrease phenobarbital effects; induction of microsomal enzymes may result in decreased effects of oral contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy); menstrual irregularities may occur

Contraindications

Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; nephritic patients

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia because adverse reactions can occur; caution in myasthenia gravis and myxedema
Patient may experience transient respiratory depression requiring ventilatory support

Sympathomimetics

These agents augment coronary and cerebral blood flow during the low flow states associated with cyanide poisoning.

Epinephrine (Adrenalin, Bronitin, EpiPen)

DOC for treating anaphylactoid reactions. Has alpha-agonist effects that include increased peripheral vascular resistance, reversed peripheral vasodilatation, systemic hypotension, and vascular permeability. Beta-agonist effects include bronchodilatation, chronotropic cardiac activity, and positive inotropic effects.

Dosing

Adult

0.1-1 mcg/min IV (1:10,000 solution), titrate to desired effect

Pediatric

Administer as in adults

Interactions

Increases toxicity of beta- and alpha-adrenergic blocking agents and that of halogenated inhalational anesthetics

Contraindications

Documented hypersensitivity; cardiac arrhythmias; angle-closure glaucoma; local anesthesia in areas such as fingers or toes because vasoconstriction may produce sloughing of tissue; do not use during labor (may delay second stage)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in elderly patients, prostatic hypertrophy, hypertension, cardiovascular disease, diabetes mellitus, hyperthyroidism, and cerebrovascular insufficiency; rapid IV infusions may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Alkalinizing agents

Used in severe poisoning, which causes marked lactic acidosis.

Sodium bicarbonate (Neut)

May be required in large doses for alkalization

Dosing

Adult

1-2 mEq/kg IV; guide repeat dosing (ideally) by ABG analysis

Pediatric

Administer as in adults

Interactions

Urinary alkalinization, induced by increased sodium bicarbonate concentrations, may cause decreased levels of lithium, tetracyclines, chlorpropamide, methotrexate, and salicylates; increases levels of amphetamines pseudoephedrine, flecainide, anorexiants, mecamylamine, ephedrine, quinidine, and quinine

Contraindications

Documented hypersensitivity; alkalosis; hypernatremia; hypocalcemia; severe pulmonary edema; unknown abdominal pain

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Only use to treat documented metabolic acidosis and hyperkalemia-induced cardiac arrest; can cause alkalosis, decreased plasma potassium, hypocalcemia and hypernatremia; caution in electrolyte imbalances, such as patients with CHF, cirrhosis, edema, corticosteroid use, or renal failure; when administering, avoid extravasation because can cause tissue necrosis

Follow-up

Further Inpatient Care

• Patients generally require admission to ICU for continuous cardiac monitoring, respiratory and cardiovascular support, and frequent neurologic evaluation.
• Rapid manifestation of acute poisoning from hydrogen cyanide gas and soluble salts causes principal acute care concerns of hemodynamic instability and cerebral edema. Conversely, acute poisoning from cyanogens (nitriles) and poorly soluble salts may not manifest or become life threatening for several hours after exposure.
• Monitor disease resolution by clinical criteria, serial plasma lactate concentrations, and arterial and venous blood gases.
• Perform serial ECGs for patients with cardiac dysrhythmias or complaints of chest pain.
• Discharge the patient when neurologic and cardiovascular status has normalized and acidosis and other metabolic abnormalities have resolved.

Further Outpatient Care

• Neurologic sequelae: Reevaluate patients within 7-10 days of discharge to monitor for onset of delayed neurologic manifestations (eg, Parkinsonlike syndrome, neuropsychiatric sequelae).

Transfer

• Avoid transfer of patients with acute cyanide toxicity.
  • Transfer the patient if antidotes and intensive care are unavailable and if rapid appropriate medical transport can be assured.
  • Provide medical stabilization (eg, airway, hemodynamic parameters) before transfer.
  • Ideally, transfer patients to a regional toxicology treatment center.

Deterrence/Prevention

• Smoke alarms significantly reduce 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.
• Determine blood cyanide concentrations or thiocyanate concentrations in patients receiving sodium nitroprusside at high doses or for more than 5 days. Alternatively, coadminister sodium thiosulfate or hydroxocobalamin to reduce the risk of iatrogenic cyanide poisoning.

Complications

• Acute and delayed neurologic manifestations (Parkinsonlike syndrome, other movement disorders, neuropsychiatric sequelae) have been reported.

Prognosis

• Prognosis is reasonably good if rapid supportive intervention and effective antidotal therapy are provided.
• Suicidal poisonings tend to have severe outcomes because large doses are often involved.

Patient Education

• 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.
  • Cyanide compounds should be scrupulously isolated from exposure to acids.
• Educate cancer and HIV patients who might purchase anticancer supplements over the Internet about possible risks of such medicines and encourage them to discuss supplement use with their oncologists.
• For excellent patient education resources, visit eMedicine's Poisoning Center and Lung and Airway Center. Also, see eMedicine's patient education articles Cyanide Poisoning, Smoke Inhalation, and Carbon Monoxide Poisoning.

Miscellaneous

Medicolegal Pitfalls

• Failure to diagnose nitrile poisoning, which may have an onset occurring hours after oral or dermal exposures has caused fatal poisoning in children after artificial fingernail remover (acetonitrile, no longer commercially available in the United States) was ingested and confused with fingernail polish remover
• Overly aggressive administration of potentially toxic antidotes (sodium nitrite or dicobalt-ethylenediaminetetraacetic acid [dicobalt EDTA]) in the absence of substantive evidence of cyanide poisoning (Dicobalt EDTA is available only in Europe.)
• Failure to promptly administer antidotal therapy when presented with clinical findings consistent with cyanide poisoning because laboratory confirmation of poisoning have not yet been received (eg, sudden collapse with severe acidosis in laboratory workers or jewelers)
• Failure to consider cyanide, a frequent toxin in smoke inhalation poisoning; treatment by oxygen alone (the standard treatment for carbon monoxide poisoning), which may not be sufficient

Special Concerns

• Pregnancy
  • Fetal demise is possible.
  • 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.

Multimedia

Media file 1: Chemical Terrorism Agents and Syndromes. Signs and symptoms. Chart courtesy of, copyright University of North Carolina at Chapel Hill, www.unc.edu/depts/spice/chemical.html.

Image available at http://img.medscape.com/pi/emed/ckb/emergency_medicine/756148-814287-910.pdf.

References

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3. 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].

4. Beamer WC, Shealy RM, Prough DS. Acute cyanide poisoning from laetrile ingestion. Ann Emerg Med. Jul 1983;12(7):449-51. [Medline].

5. Borron SW, Baud FJ. Acute cyanide poisoning: clinical spectrum, diagnosis, and treatment. Arh Hig Rada Toksikol. Sep 1996;47(3):307-22. [Medline].

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Keywords

cyanide toxicity, cyanide poisoning, cyanide exposure, nitrile poisoning, prussic acid, hydrocyanic acid, hydrogen cyanide, cyanogens, HCN

Contributor Information and Disclosures

Author

Inna Leybell, MD, Staff Physician, Department of Emergency Medicine, Bellevue Hospital, New York University Hospital
Inna Leybell, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Medical Student Association/Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Robert S Hoffman, MD, FAACT, FACMT, Associate Professor, Departments of Emergency Medicine and Medicine, Clinical Pharmacology, New York University School of Medicine, Consulting Staff, Department of Emergency Services, Bellevue and New York University Hospital
Robert S Hoffman, MD, FAACT, FACMT is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, American College of Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Stephen W Borron, MD, MS, FACEP, FACMT, Clinical Professor of Emergency Medicine, Surgery, Consultant to the South Texas Poison Center, University of Texas Health Science Center at San Antonio; President and Chief Medical Officer of International Toxicology Consultants
Stephen W Borron, MD, MS, FACEP, FACMT is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, American Industrial Hygiene Association, and European Association of Poisons Centres and Clinical Toxicologists
Disclosure: Dey, L.P. Consulting fee Consulting; Merck Sante Grant/research funds Laboratory research; Dey, L.P. Honoraria Speaking and teaching

Medical Editor

David C Lee, MD, Research Director, Department of Emergency Medicine, Assistant Professor, North Shore University Hospital and New York University Medical School
David C Lee, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Director of Pharmacy, Sacred Heart Hospital
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

John G Benitez, MD, MPH, FACMT, FACPM, FAAEM, Associate Professor, Department of Medicine, Clinical Pharmacology Division, Vanderbilt University; Managing Director, Tennessee Poison Center
John G Benitez, MD, MPH, FACMT, FACPM, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Department of Surgery, Section of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

The authors and editors of eMedicine gratefully acknowledge the contributions of previous author, Frederic Baud, MD, to the development and writing of this article.

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