Cyanide Toxicity Treatment & Management
- Author: Inna Leybell, MD; Chief Editor: Asim Tarabar, MD more...
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.[23, 24]
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. Delayed onset of Parkinson-like syndrome or neuropsychiatric sequelae may be noted on followup.
Special concerns in pregnancy
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[5, 6] :
Rescue from the cyanide source (on the assumption that rescuers have the highest level of respiratory protection [level A])
Removal of contaminated clothing and decontamination of the skin as required with soap and water
Administration of high-flow oxygen, airway management, and ventilatory support as required
Establishment of intravenous (IV) access
Continuous cardiac monitoring
Advanced cardiac life support (ACLS) measures as indicated for dysrhythmias
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.[26, 23, 24] 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.
Emergency Department Care
Initial emergency department care for patients with cyanide exposure is identical to that provided in the prehospital phase. Provide supportive care, including the following:
Airway control, ventilation, and 100% oxygen
Crystalloids and vasopressors, as needed, for hypotension
Sodium bicarbonate, titrated according to arterial blood gas (ABG) and serum bicarbonate level
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.[27, 28] 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. 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.
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). It can also interfere with hemodialysis.
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
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.
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.
Deterrence and Prevention
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. 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).
Consult with law enforcement authorities and the Federal Bureau of Investigation (FBI) in any suspected terrorist incident.
Armstrong J. Chemical warfare. RN. 2002 Apr. 65(4):32-9; quiz 40. [Medline].
Brennan RJ, Waeckerle JF, Sharp TW, Lillibridge SR. Chemical warfare agents: emergency medical and emergency public health issues. Ann Emerg Med. 1999 Aug. 34(2):191-204. [Medline].
Akyildiz BN, Kurtoglu S, Kondolot M, Tunc A. Cyanide poisoning caused by ingestion of apricot seeds. Ann Trop Paediatr. 2010. 30(1):39-43. [Medline].
Baud FJ. Cyanide: critical issues in diagnosis and treatment. Hum Exp Toxicol. 2007 Mar. 26(3):191-201. [Medline].
Greenfield RA, Brown BR, Hutchins JB, Iandolo JJ, Jackson R, Slater LN, et al. Microbiological, biological, and chemical weapons of warfare and terrorism. Am J Med Sci. 2002 Jun. 323(6):326-40. [Medline].
Rosenbloom M, Leikin JB, Vogel SN, Chaudry ZA. Biological and chemical agents: a brief synopsis. Am J Ther. 2002 Jan-Feb. 9(1):5-14. [Medline].
Baskin SI, Brewer TG. Cyanide poisoning. Cyanide poisoning. Medical Aspects of Chemical and Biological Warfare. 1997. 271-286.
Morocco AP. Cyanides. Crit Care Clin. 2005 Oct. 21(4):691-705, vi. [Medline].
Sidell FR, Patrick WC, Dashiell TR. Cyanide. Jane's Chem-Bio Handbook. 1998. 79-88.
USACHPPM. Cyanide. USACHPPM Tech Guide 244: The Medical NBC Battlebook. 1999. V: 36-37.
Burda AM, Sigg T. Pharmacy preparedness for incidents involving weapons of mass destruction. Am J Health Syst Pharm. 2001 Dec 1. 58(23):2274-84. [Medline].
Lynch EL, Thomas TL. Pediatric considerations in chemical exposures: are we prepared?. Pediatr Emerg Care. 2004 Mar. 20(3):198-208. [Medline].
Zheng A, Dzombak DA, Luthy RG. Formation of free cyanide and cyanogen chloride from chloramination of publicly owned treatment works secondary effluent: laboratory study with model compounds. Water Environ Res. 2004 Mar-Apr. 76(2):113-20. [Medline].
Schnepp R. Cyanide: sources, perceptions, and risks. J Emerg Nurs. 2006 Aug. 32(4 Suppl):S3-7. [Medline].
Musshoff F, Schmidt P, Daldrup T, Madea B. Cyanide fatalities: case studies of four suicides and one homicide. Am J Forensic Med Pathol. 2002 Dec. 23(4):315-20. [Medline].
National Cancer Institute. Cancer topics: Laetrile/Amygdalin. 11/21/2005. [Full Text].
Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 32nd Annual Report. Clin Toxicol (Phila). 2015 Dec. 53 (10):962-1147. [Medline]. [Full Text].
Department of the Army. Blood agents (Cyanogens). Field Manual 8-285: Treatment of Chemical Agent Casualties and Conventional Military Chemical Injuries. 1995. VI: 1-2.
Baud FJ, Borron SW, Mégarbane B, Trout H, Lapostolle F, Vicaut E, et al. Value of lactic acidosis in the assessment of the severity of acute cyanide poisoning. Crit Care Med. 2002 Sep. 30(9):2044-50. [Medline].
Baud FJ, Barriot P, Toffis V, Riou B, Vicaut E, Lecarpentier Y, et al. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med. 1991 Dec 19. 325(25):1761-6. [Medline].
Lee J, Mukai D, Kreuter K, et al. Potential interference by hydroxocobalamin on co-oximetry hemoglobin measurements during cyanide and smoke inhalation treatments. Ann Emerg Med. 2007. 49(6):802-805. [Medline].
Fortin JL, Desmettre T, Manzon C, Judic-Peureux V, Peugeot-Mortier C, Giocanti JP, et al. Cyanide poisoning and cardiac disorders: 161 cases. J Emerg Med. 2010 May. 38(4):467-76. [Medline].
USAMRICD. Cyanide. Field Management of Chemical Casualties Handbook. 1996. 37-40.
USAMRICD. Cyanide. Medical Management of Chemical Casualties Handbook. 1999. 38-58.
Martin CO, Adams HP Jr. Neurological aspects of biological and chemical terrorism: a review for neurologists. Arch Neurol. 2003 Jan. 60(1):21-5. [Medline].
Kirk MA, Gerace R, Kulig KW. Cyanide and methemoglobin kinetics in smoke inhalation victims treated with the cyanide antidote kit. Ann Emerg Med. 1993 Sep. 22(9):1413-8. [Medline].
Borron SW, Baud FJ, Mégarbane B, Bismuth C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg Med. 2007 Jun. 25(5):551-8. [Medline].
Borron SW, Baud FJ, Barriot P, Imbert M, Bismuth C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg Med. 2007 Jun. 49(6):794-801, 801.e1-2. [Medline].
DesLauriers CA, Burda AM, Wahl M. Hydroxocobalamin as a cyanide antidote. Am J Ther. 2006 Mar-Apr. 13(2):161-5. [Medline].
Hall AH, Saiers J, Baud F. Which cyanide antidote?. Crit Rev Toxicol. 2009. 39(7):541-52. [Medline].
Curry SC, Connor DA, Raschke RA. Effect of the cyanide antidote hydroxocobalamin on commonly ordered serum chemistry studies. Ann Emerg Med. 1994 Jul. 24(1):65-7. [Medline].
Sutter M, Tereshchenko N, Rafii R, Daubert GP. Hemodialysis Complications of Hydroxocobalamin: A Case Report. J Med Toxicol. 2010 Mar 30. [Medline].
Shepherd G, Velez LI. Role of hydroxocobalamin in acute cyanide poisoning. Ann Pharmacother. 2008 May. 42(5):661-9. [Medline].