Smoking is deadly

aka Toxicology Conundrum 038

A 37 year-old man is BIBA to the emergency department following a fire at his apartment. He has a fluctuating level of consciousness (currently GCS 11) and is hypotensive (BP 85/50). He has no evidence of airway compromise, burns or other significant injury.

A venous gas shows that he has a COHb of 21% and a lactate of 14 mmol/L.

Can you keep this man alive?


Q1. What is the likely diagnosis and what is the significance of the lactate of 14 mmol/L in this setting?

Answer and interpretation

Smoke inhalation resulting in cyanide and carbon monoxide poisoning.

Of course other toxic chemicals are produced by the combustion of natural and synthetic materials in a house fire, but these are the two most important toxins to be aware of.

In the absence of severe burns, there is a strong correlation between the severity of cyanide intoxication and serum lactate. For instance, a serum lactate > 10 mmol/L predicts a cyanide level >40 micromol/L with a sensitivity of 87% and a specificity of 94% (positive likelihood ratio of 14.5 and a negative likelihood ratio of 0.14).

Cyanide levels help confirm the diagnosis in retrospect (take blood in a heparinsed tube):

  • >20 microM — symptomatic
  • >40 microM — potentially toxic
  • >100 microM — lethal

Q2. What is the the significance of the COHb of 21%?

Answer and interpretation

An elevated carboxyhemoglobin level confirms the diagnosis of carbon monoxide toxicity, but the level only loosely correlates with the severity of symptoms following exposure.

Smokers may have a baseline COHb level up to about 10%. A general guide to the clinical features at different levels is:

  • 10% — asymptomatic or mild headache
  • 20% — dizziness, nausea, dyspnea, throbbing headache
  • 30% — vertigo, ataxia, altered vision
  • 40% — confusion, coma, seizures, syncope
  • 50% — arryhthmias, seizures, cardiorespiratory arrest

Q3. What are the mechanisms of toxicity for these agents?

Answer and interpretation

Carbon monoxide

  • binds hemoglobin with >200 times the affinity of oxygen, resulting in ‘anemic hypoxia’ (reduced ability of the blood to carry oxygen).
  • binds to intracellular cytochromes and myoglobin, which contributes to ‘histotoxic hypoxia’ (reduced ability of the blood to utilise oxygen).
  • initiates endothelial oxidative injury, lipid peroxidation and an inflammatory cascade (probably an important contributor to delayed neuropsychiatric sequelae).


  • binds the ferric (Fe3+) ion of cytochrome oxidase causing ‘histotoxic hypoxia’ and lactic acidosis.
  • stimulates biogenic amine release causing pulmonary and coronary vasoconstriction.
  • stimulates neurotransmitter release, such as N-methyl-D-aspartate (NMDA), causing neurotoxicity and seizures.

Q4 What specific treatment should be given for the COHb of 21%?

Answer and interpretation


In the first instance, high flow oxygen via a non-rebreather mask (as close to 100% oxygen as possible) should be administered (unless intubation and ventilation is indicated). The administration of oxygen enhances the elimination of CO, which depends on the dissolved oxygen tension in the blood.

Approximate elimination half-lives of CO when treated with:

  • room air — 240 min
  • 100% oxygen — 90 min
  • hyperbaric oxygen (100% oxygen at 3 atmospheres) — 23 minutes

Hyperbaric oxygen should always be considered in patients with risk factors for neuropsychiatric sequelae and in the pregnant patient. However, despite a number of trials the indications and effectiveness of this therapy are unclear. In critically ill patients the administration of hyperbaric oxygen may present major logistical problems.

Oxygen should be administered until all symptoms have resolved.

Q5. What treatment(s) should be considered for the likely cause of the hyperlactemia?

Answer and interpretation

The relative efficacy of different cyanide antidotes is not well defined.

However, most authorities recommend administration of an antidote if cyanide poisoning is suspected and there evidence of serious clinical toxicity (i.e. altered mental status, seizures, hypotension or metabolic acidosis).

The main cyanide antidotes that may be given in the emergency department 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.

First, let’s consider dicobalt edetate:

  • 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.

And now, 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.

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. It’s onset of action may be too slow if used alone for severe cyanide toxicity.

Methemoglobin generators are effectively contra-indicated in the setting of smoke inhalation and possible carbon monoxide poisoning as they are likely to aggravate tissue hypoxia.

“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.

Q6. What is the patient’s prognosis?

Answer and interpretation

Deaths from both cyanide toxicity and CO poisoning tend to occur rapidly, prior to arrival at an emergency department. For those that arrive at hospital alive survival is likely even if only oxygen and meticulous supportive care is provided. Depending on the duration and severity of tissue hypoxia, multiple organ dysfunction syndrome (MODS) may  the patient’s recovery.

The patient is at risk of longer term neuropsychiatric sequelae.

Loss of consciousness, persistent neurological dysfunction and metabolic acidosis are all high risk features for neuropsychiatric sequelae in the context of CO poisoning (other risk factors include age >55 years and cerebellar signs — although in this case the picture is further complicated by the co-existence of cyanide toxicity). Appropriate follow up is necessary, and in severe cases an MRI may show evidence of demyelination, basal ganglia injury, cerebral edema or atrophy. Similar longterm complications may occur as a result of severe cyanide poisoning.

  • EMCrit — Podcast 122 – Cardiac Arrest after the Toxicology of Smoke Inhalation with Lewis Nelson (2014)
  • ICU Rounds — Smoke Inhalation Injury: CO and Cyanide Toxicity
  • 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. Epub 2007 May 4. 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.
  • Silver S, Smith C, Worster A; BEEM (Best Evidence in Emergency Medicine) Team. Should hyperbaric oxygen be used for carbon monoxide poisoning? CJEM. 2006 Jan;8(1):43-6. PMID: 17175630.


Toxicology Conundrum

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.

| INTENSIVE | RAGE | Resuscitology | SMACC

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