eMedicine Specialties > Emergency Medicine > Toxicology
Toxicity, Cyanide: Treatment & Medication
Updated: Dec 17, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
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.
- Cyanide Antidote Kit contains amyl nitrite pearls, sodium nitrite, 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
Documented hypersensitivity
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
None reported
Documented hypersensitivity
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)
None reported
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
Documented hypersensitivity
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 |
| « Previous Page | Next Page » |
References
American Association of Poison Control Centers. Annual Reports of the Toxic Exposure Surveillance System. [Full Text].
National Cancer Institute. Cancer topics: Laetrile/Amygdalin. 11/21/2005;[Full Text].
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].
Beamer WC, Shealy RM, Prough DS. Acute cyanide poisoning from laetrile ingestion. Ann Emerg Med. Jul 1983;12(7):449-51. [Medline].
Borron SW, Baud FJ. Acute cyanide poisoning: clinical spectrum, diagnosis, and treatment. Arh Hig Rada Toksikol. Sep 1996;47(3):307-22. [Medline].
Borron SW, Baud FJ, Barriot P, et al. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. Jun 2007;49(6):794-801, 801.e1-2. [Medline].
Borron SW, Baud FJ, Megarbane B, et al. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg Med. Jun 2007;25(5):551-8. [Medline].
Clark CJ, Campbell D, Reid WH. Blood carboxyhaemoglobin and cyanide levels in fire survivors. Lancet. Jun 20 1981;1(8234):1332-5. [Medline].
Forsyth JC, Mueller PD, Becker CE, et al. Hydroxocobalamin as a cyanide antidote: safety, efficacy and pharmacokinetics in heavily smoking normal volunteers. J Toxicol Clin Toxicol. 1993;31(2):277-94. [Medline].
Hall AH, Dart R, Bogdan G. Sodium thiosulfate or hydroxocobalamin for the empiric treatment of cyanide poisoning?. Ann Emerg Med. Jun 2007;49(6):806-13. [Medline].
Hall AH, Rumack BH. Hydroxycobalamin/sodium thiosulfate as a cyanide antidote. J Emerg Med. 1987;5(2):115-21. [Medline].
Kerns W II, Isom G, Kirk MA. Cyanide and Hydrogen Sulfide. In: in Goldfrank's Toxicologic Emergencies. 7th ed. 2002:1498-1504.
Mannaioni G, Vannacci A, Marzocca C, et al. Acute cyanide intoxication treated with a combination of hydroxycobalamin, sodium nitrite, and sodium thiosulfate. J Toxicol Clin Toxicol. 2002;40(2):181-3. [Medline].
Mueller M, Borland C. Delayed cyanide poisoning following acetonitrile ingestion. Postgrad Med J. May 1997;73(859):299-300. [Medline].
O'Brien B, Quigg C, Leong T. Severe cyanide toxicity from 'vitamin supplements'. Eur J Emerg Med. Oct 2005;12(5):257-8. [Medline].
Salkowski AA, Penney DG. Cyanide poisoning in animals and humans: a review. Vet Hum Toxicol. Oct 1994;36(5):455-66. [Medline].
Sauer SW, Keim ME. Hydroxocobalamin: improved public health readiness for cyanide disasters. Ann Emerg Med. Jun 2001;37(6):635-41. [Medline].
Way JL. Cyanide intoxication and its mechanism of antagonism. Annu Rev Pharmacol Toxicol. 1984;24:451-81. [Medline].
Further Reading
Keywords
cyanide toxicity, cyanide poisoning, cyanide exposure, nitrile poisoning, prussic acid, hydrocyanic acid, hydrogen cyanide, cyanogens, HCN
