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Toxicity, Cyanide: Treatment & Medication

Author: Inna Leybell, MD, Staff Physician, Department of Emergency Medicine, North Shore University Hospital
Coauthor(s): Stephen W Borron, MD, MS, FACEP, FACMT, Professor of Emergency Medicine and Medical Toxicology, Division of Medical Toxicology, Department of Emergency Medicine, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center; Associate Medical Director, West Texas Regional Poison Center
Contributor Information and Disclosures

Updated: Dec 17, 2008

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.

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

Methylene blue will counteract methemoglobin formation

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.

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

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.

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)

Documented hypersensitivity; hereditary optic nerve atrophy

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).

Adult

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

Pediatric

Not established

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

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.

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

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

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

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.

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

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

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

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.

Adult

10-20 mg/kg IV over 20 min

Pediatric

10-20 mg/kg IV over 20 min

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

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

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.

Adult

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

Pediatric

Administer as in adults

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

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)

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

Adult

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

Pediatric

Administer as in adults

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

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

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

More on Toxicity, Cyanide

Overview: Toxicity, Cyanide
Differential Diagnoses & Workup: Toxicity, Cyanide
Treatment & Medication: Toxicity, Cyanide
Follow-up: Toxicity, Cyanide
Multimedia: Toxicity, Cyanide
References

References

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Further Reading

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, North Shore University Hospital
Inna Leybell, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Student Association/Foundation, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Coauthor(s)

Stephen W Borron, MD, MS, FACEP, FACMT, Professor of Emergency Medicine and Medical Toxicology, Division of Medical Toxicology, Department of Emergency Medicine, Paul L Foster School of Medicine, Texas Tech University Health Sciences Center; Associate Medical Director, West Texas Regional Poison Center
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, Associate 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, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals
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, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

 
 
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