Case Files of the University of Massachusetts Toxicology Fellowship: Does This Smoke Inhalation Victim Require Treatment with Cyanide Antidote?

Hamad, Eike; Babu, Kavita M.; Bebarta, Vikhyat S.

doi:10.1007/s13181-016-0533-0

Cited by 12 publications

(13 citation statements)

References 43 publications

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“…Therefore the triad of lactate >7 mmol/L, elevated anion gap acidosis and reduced arterio-venous oxygen gradient can be used as both an indicator for cyanide toxicity and monitoring of treatment effect 9. A central venous oxygen saturation >90% that decreases on administration of antidote is specific for cyanide poisoning due to arteriolisation of venous blood following histotoxic hypoxia 4. This requires early central venous access prior to commencement of treatment, something that was not available in this case.…”

Section: Discussionmentioning

confidence: 94%

“…Sodium thiosulfate does not interfere with oxygen delivery and has a very low toxicity,15 however it also has a delayed onset of action, a short half-life and poor penetration of mitochondria. It can also cause hypotension, increased bleeding time and vomiting 4. Sodium thiosulfate lacks human trials demonstrating efficacy as a sole treatment17 and has been found ineffective in animal models for severe cyanide poisoning.…”

Section: Discussionmentioning

confidence: 99%

“…Smoke inhalation is implicated in 75% of fire-related deaths in the USA,1 and progresses to respiratory complications in 73% of cases, and acute respiratory distress syndrome in 20% 2. Although carbon monoxide poisoning remains the most common cause of fatality from smoke inhalation, causing 80% of deaths,3 cyanide is present in the blood of 60% of fire-related fatalities4 and fire is the most common cause of cyanide poisoning 5. Incidences of cyanide poisoning are decreasing due to changing composition of domestic furnishings, but the above statistics and the paucity of data and case reports on the subject suggest it is still underdiagnosed.…”

Section: Introductionmentioning

confidence: 99%

“…Cyanide binds to cobalt, ferric iron in methaemoglobin, cytochrome oxidase and ferrous iron in haemoglobin, due to its high affinity for metalloproteins 7. The non-competitive cytochrome inhibition causes cessation of oxidative phosphorylation and anaerobic respiration4 leading to a depletion of adenosine triphosphate (ATP) and lactic acidaemia.…”

Section: Introductionmentioning

confidence: 99%

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Toxic inhalational injury

2020

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A middle-aged patient presented with toxic inhalational injury, and was resuscitated prehospitally and treated in the emergency department for smoke inhalation, carbon monoxide (CO) exposure and cyanide poisoning with the use of antidotes. Due to the CO effects on spectrophotometry, an anaemia initially identified on blood gas analysis was thought to be artefactual, but was later confirmed by laboratory testing to be accurate. In addition, cyanide can confound haemoglobin testing due to its use in the analytical process and non-cyanide analysis is required when there is suspected exposure. Although no consensus exists on a first-line cyanide antidote choice, hydroxocobalamin is the only antidote without a serious side effect profile and/or deleterious cardiovascular effects. We propose prehospital enhanced care teams consider carrying hydroxocobalamin for early administration in toxic inhalational injury.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Toxic inhalational injury

2020

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“…The use of chemical weapons in attacks on civilians has increased markedly over the last decade, but there has been little progress in the clinical development and use of novel highly effective antidotes for treatment. The use of hydroxocobalamin has been heavily promoted for treatment of cyanide toxicity [6,8,9,[34][35][36] but there is little comparative evidence on efficacy. In this study of minipigs poisoned with a rapid intravenous infusion of potassium cyanide, although both hydroxocobalamin and dicobalt edetate showed some efficacy at minimally toxic doses, neither were highly effective.…”

Section: Discussionmentioning

confidence: 99%

Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning

Thompson

Dunn

Jefferson

et al. 2019

Clinical Toxicology

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Background: Dicobalt edetate and hydroxocobalamin are widely used to treat hydrogen cyanide poisoning. However, comparative and quantitative efficacy data are lacking. Although post-exposure treatment is typical, it may be possible to administer these antidotes before exposure to first attenders entering a known site of cyanide release, as supplementary protection to their personal protective equipment. Methods: We established an anaesthetised Gottingen minipig model of lethal bolus potassium cyanide (KCN) injection to simulate high dose hydrogen cyanide inhalation. Doses were similar to human lethal doses of KCN. Dicobalt edetate and hydroxocobalamin were administered shortly before KCN and their effect on metabolic and cardiovascular variables and survival time were measured. Results: Increases in arterial lactate were similar after 0.08 and 0.12 mmol/kg KCN. KCN 0.08 mmol/kg was survived by 4/4 animals with moderate cardiovascular effects, while the 0.12 mmol/kg dose was lethal in 4/4 animals, with a mean time to euthanasia of 28.3 (SEM: 13.9) min. Administration of dicobalt edetate (0.021 mmol/kg, 8.6 mg/kg) or hydroxocobalamin (0.054 mmol/kg, 75 mg/kg) at clinically licenced doses had modest effect on lactate concentrations but increased survival after administration of KCN 0.12 mmol/kg (survival: dicobalt edetate 4/4, hydroxocobalamin 2/4) but not 0.15 mmol/kg (0/4 and 0/4, respectively). In a subsequent larger study, doubling the dose of hydroxocobalamin (0.108 mmol/kg, 150 mg/kg) was associated with a modest but inconsistent increased survival after 0.15 mmol/kg KCN (survival: control 0/8, 75 mg/kg 1/10, 150 mg/kg 3/10) likely due to variable pharmacokinetics. Conclusions: In this porcine study of cyanide exposure, with pre-exposure antidote administration, licenced doses of dicobalt edetate and hydroxocobalamin were effective at just lethal doses but ineffective at less than twice the estimated LD 50. The efficacy of a rapidly-administered double-dose of hydroxocobalamin was limited by variable pharmacokinetics. In clinical poisoning scenarios, with delayed administration, the antidotes are likely to be even less effective. New antidotes are required for treatment of cyanide exposures appreciably above the minimum lethal dose.

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Cyanide-Binding Antidotes: Dicobalt Edetate and Hydroxycobalamin

Bebarta¹

2017

Critical Care Toxicology

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Case Files of the University of Massachusetts Toxicology Fellowship: Does This Smoke Inhalation Victim Require Treatment with Cyanide Antidote?

Cited by 12 publications

References 43 publications

Toxic inhalational injury

Toxic inhalational injury

Modest and variable efficacy of pre-exposure hydroxocobalamin and dicobalt edetate in a porcine model of acute cyanide salt poisoning

Cyanide-Binding Antidotes: Dicobalt Edetate and Hydroxycobalamin

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