Reviewed and revised 20 May 2016
- Cyanide is a potentially lethal toxic agent that can be found in liquid and gaseous form.
- First discovered in 1786 by Scheele, who extracted it from the dye Prussian blue – and promptly died from exposure to the vapours
- Average lethal dose of prussic acid (hydrogen cyanide, HCN) taken by mouth between 60 and 90 mg (adult)
- this corresponds to about 1 teaspoonful of a 2% solution of hydrocyanic acid and to about 200 mg of potassium cyanide
- Smoke inhalation (fires burning plastics, wools, silk and other natural and synthetic polymers)
- Cyanogenic glycosides such as amygdalin (e.g. almonds, apricot kernels and other Prunus species such as peach, apple, cherry and plum)
- Sodium nitroprusside
- Industrial exposure (e.g. cyanide salts used in metal extraction and refining, electroplating, photography and fumigation)
- acetonitrile (industrial solvent used as cosmetic remover and in laboratories)
- Chemical warfare and acts of terrorism (e.g. deliberate contamination of medications and food)
- Poison for feral animal control (e.g. rodenticide)
- Alternative medicines (e.g. derived from apricot kernels)
- Fumigant in airplanes, buildings, ships
Mechanisms of toxicity include:
- binds the ferric (Fe3+) ion of cytochrome oxidase causing ‘histotoxic hypoxia’ and lactic acidosis
- stimulates biogenic amine release causing pulmonary and coronary vasoconstriction, which results in pulmonary edema and heart failure
- stimulates neurotransmitter release, such as N-methyl-D-aspartate (NMDA), causing neurotoxicity and seizures
- Acetonitrile is slowly metabolised by the liver and may lead to cyanide toxicity over 24 hours
- Amygdalin is hydrolysed by two enzymes (amygdalin hydrolase and prunasin hydrolase) most effectively in crushed, moistened kernels, resulting in the formation of HCN and glucose
- Sodium nitroprusside, metabolised to cyanide and may accumulate with prolonged high dose infusions
- Cyanide is rapidly absorbed and taken up into cells
- volume of distribution of 1.5 L/kg
- highly protein bound
- Cyanide is metabolised via the liver enzyme rhodanese (named before international enzyme nomenclature was standardised, hence -ese not -ase!)
- Rhodanese catalyses the reaction of CN + thiosulfate to form thiocyanate and sulphite
- Thiocyanate is non-toxic (unless it accumulates with high levels) and is excreted in the urine
- The body’s supply of thiosulfate is limited so it is the rate limiting step in cyanide metabolism
- The elimination half-life of cyanide is 2-3 hours
Acute inhalation or ingestion
- rapid loss of consciousness and seizures with inhalation
- onset of symptoms over ~30 minutes with ingestion (depending on the dose)
Milder exposures result in non-specific features including:
- nausea, vomiting, headache, dyspnoea, increased respiratory rate, hypertension, tachycardia, altered level of consciousness and seizures
- Progressive features will result from end-organ damage secondary to anaerobic respiration and histotoxic hypoxia
- hypotension, bradycardia, reduced GCS and respiratory depression, cardiovascular collapse
- may appear ‘pink’ due to high SvO2 following oxygen administration
- smell of bitter almonds may be present (not everyone can detect or recognise this smell!)
Consider cyanide toxicity as the diagnosis in patients who collapse with a raised lactate level
- lactate >10 mmol/L
- in patients without severe burns, this corresponds to a cyanide level of > 40 micromol/L
- sensitivity of 87% and a specificity of 94% (positive likelihood ratio of 14.5 and a negative likelihood ratio of 0.14)
- high SvO2 with oxygen administration (poor oxygen extraction)
- COHb (suspect coexistent carbon monoxide poisoning if smoke inhalation)
- help confirm the diagnosis in retrospect (take blood in a heparinsed tube), turn around times mean they are not useful in the acute setting
- Cyanide is concentrated 10 fold by RBCs, therefore whole blood levels give the best information on the potential for a toxic level.
- levels correlate with clinical severity
- >20 microM — symptomatic
- >40 microM — potentially toxic
- >100 microM — lethal
Removal from the source
- Cyanide is a potential danger to healthcare workers through the dermal route and through inhalation
- Patient vomitus can liberate hydrogen cyanide gas
- Avoid mouth-to-mouth/nose ventilation
- attend to ABCs and administer high flow oxygen
- provide haemodynamic support
- inotropes/ vasopressors
- consider extracorporeal support
- give antidote if suspected toxicity
- hydroxocobalamin then sodium thiosulfate is generally preferred if available (see below)
Supportive care and monitoring
- cases that survive to hospital typically will typically recover with supportive care, even in the absence of antidotal therapy
Seek and treat underlying causes and complications
- address suicidality if appropriate
- address burns and injuries if due to smoke inhalation
- Remove any contaminated clothing and bag these
- Wash contaminated skin with soap and water
- Avoid activated charcoal unless intubated
- see below
- Asymptomatic patients with normal blood gases can be discharged at 6 hours
- Critically ill patients will require ICU admission
- Consult a clinical toxicologist early
“Hydroxocobalamin is an antidote that seems to have many of the characteristics of the ideal cyanide antidote: rapid onset of action, neutralizes cyanide without interfering with cellular oxygen use, tolerability and safety profiles conducive to prehospital use, safe for use with smoke-inhalation victims, not harmful when administered to non-poisoned patients, easy to administer.”
— Hall et al, 2009
Most authorities recommend administration of an antidote if cyanide poisoning is suspected and there evidence of serious clinical toxicity
- features: altered mental status, seizures, hypotension or metabolic acidosis
- relative efficacy of different cyanide antidotes is not well defined
The main cyanide antidotes that may be given are:
- Cobalt-containing cyanide binders
- dicobalt edetate and hydroxocobalamin (the latter forms cyanocobalamine).
- Sulfur donors
- such as sodium thiosulfate, which acts as a sulfur donor to the endogenous rhodanese enzyme that detoxifies cyanide by converting it to thiocyanate
- Methemoglobin generators
- oxidants such as amyl nitrite (inhaled), sodium nitrite (IV) and dimethyl aminophenol (IV/IM) convert hemoglobin (Fe2+) to methemoglobin (Fe3+) which binds cyanide forming cyanhemoglobin.
- Dicobalt edetate is administered 300 mg IV (7.5 mg/kg in children) over 1 minute followed by 50 mL of 50% glucose.
- This is repeated up to 3 times if an immediate clinical response is not seen.
- This cobalt salt is toxic — it causes seizures, chest pain and dyspnoea, head and neck swelling, hypotension, urticaria and vomiting. Due to this toxicity it should only be given if severe cyanide poisoning is strongly suspected.
Hydroxocobalamin and thiosulfate:
- If available, hydroxocobalamin together with thiosulfate (but do not mix them in the same infusion as they will form a complex!) may be a better option as they are much less toxic than dicobalt edetate
- administer 5g hydroxocobalamin diluted in 200 mL of 5% dextrose IV over 30 minutes (binds 100mg cyanide — use a larger inital dose if necessary)
- then administer 12.5g sodium thiosulfate (50 mL of 25% solution) IV over 10 minutes
- repeat both doses if there is no improvement within 15 minutes
- Adverse effects of these agents are:
- hydroxocobalamin — occasional hypertension, bradycardia or tachycardia (not requiring treatment), orange-red skin and body fluid discolouration (benign, lasts up to 48 hours)
- sodium thiosulfate — nausea and vomiting with rapid injection; minor nonspecific effects such as hypotension, headache, abdominal pain and confusion
- effectively contra-indicated in the setting of smoke inhalation and possible carbon monoxide poisoning as they are likely to aggravate tissue hypoxia
Unfortunately the use of hydrocobalamin in many settings is limited by the poor availability of the 5g/100 mL vials in many settings — they are widely used and produced in France.
- Consider just giving sodium thiosulfate together with oxygen and meticulous supportive care in doubtful cases of mild-to-moderate severity cyanide toxicity – onset of action may be too slow if used alone for severe cyanide toxicity
As cyanide is generally rapidly lethal, paramedics should be trained in the pre-hospital administration of cyanide antidotes in regions or situations where poisoning can be anticipated. antidotes should be stored in high areas (e.g. at relevant industrial sites)
References and links
- Flashcards – Cyanide poisoning
- Baud FJ, Barriot P, Toffis V, Riou B, Vicaut E, Lecarpentier Y, Bourdon R, Astier A, Bismuth C. Elevated blood cyanide concentrations in victims of smoke inhalation. N Engl J Med. 1991 Dec 19;325(25):1761-6. PMID: 1944484.
- 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. PMID: 17481777.
- Cescon DW, Juurlink DN. Discoloration of skin and urine after treatment with hydroxocobalamin for cyanide poisoning. CMAJ. 2009 Jan 20;180(2):251. PMC2621289.
- Cummings TF. The treatment of cyanide poisoning. Occup Med (Lond). 2004 Mar;54(2):82-5. PMID: 15020725.
- Hall AH, Saiers J, Baud F. Which cyanide antidote? Crit Rev Toxicol. 2009;39(7):541-52. Review. PMID: 19650716.
- Mutlu GM, Leikin JB, Oh K, Factor P. An unresponsive biochemistry professor in the bathtub. Chest. 2002 Sep;122(3):1073-6. PMID: 12226056.
Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also a Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.
After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.
He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE. He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.
His one great achievement is being the father of three amazing children.
On Twitter, he is @precordialthump.