Smoking is deadly

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

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

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).

Cyanide

• 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.

Oxygen!

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.

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.

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.