Hydroxocobalamin in cyanide poisoning

Thompson, John Paul; Marrs, Timothy C.

doi:10.3109/15563650.2012.742197

Cited by 80 publications

(49 citation statements)

References 64 publications

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“…Intravenous sodium nitrite and inhaled amyl nitrite are methemoglobin generators, and methemoglobin’s strong affinity for cyanide binding is the rationale for their use as antidotes (165). Hydroxycobalamin is a vitamin B derivative that is available intravenously and contains a cobalt moiety that avidly binds to intracellular cyanide forming cyanocobalamin (165–167). Sulfanegen sodium is a prodrug of 3-mercaptopyruvate that converts cyanide to thiocyanate (164,168).…”

Section: Adverse Effects Of Nitratesmentioning

confidence: 99%

The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics

Divakaran

Loscalzo

2017

Journal of the American College of Cardiology

120

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The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a biological effector and better understanding of its roles in vasodilation, cell permeability, platelet function, inflammation, and other vascular processes have advanced our knowledge of the hemodynamic (mostly mediated through vasodilation of capacitance and conductance arteries) and non-hemodynamic effects of organic nitrate therapy, via both nitric oxide-dependent and independent mechanisms. Nitrates are rapidly absorbed from mucous membranes, the gastrointestinal tract, and the skin, and, thus, nitroglycerin is available in several preparations for delivery via several routes: oral tablets, sublingual tablets, buccal tablets, sublingual spray, transdermal ointment, and transdermal patch; it is also available in intravenous formulations. The organic nitrates are commonly used in the treatment of cardiovascular disease, but clinical data limit their use mostly to the treatment of angina. They are also used in the treatment of subsets of patients with heart failure and pulmonary hypertension. One major problem with the use of nitrates is the development of tolerance. Although several agents have been studied for use in the prevention of nitrate tolerance, none are currently recommended owing to a paucity of supportive clinical data. Only one method of preventing nitrate tolerance remains widely accepted: the use of a dosing strategy that provides an interval of no or low nitrate exposure during each 24-hour period. Nitric oxide’s important role in several cardiovascular disease mechanisms continues to drive research toward finding novel ways to affect both endogenous and exogenous sources of this key molecular mediator.

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Section: Adverse Effects Of Nitratesmentioning

confidence: 99%

The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics

Divakaran

Loscalzo

2017

Journal of the American College of Cardiology

120

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“…1–3 However, because of its poor water solubility, it must be administered in a relatively large volume intravenously. In the out-of-hospital setting of cyanide gas release, such as an industrial accident, terrorist attack, or commercial or residential fire, intravenous access can be difficult and particularly problematic for providers wearing hazardous material protective gear; thus, nonintravenous antidotes are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Intravenous Cobinamide Versus Hydroxocobalamin for Acute Treatment of Severe Cyanide Poisoning in a Swine (Sus scrofa) Model

Bebarta

Tanen

Boudreau

et al. 2014

Annals of Emergency Medicine

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Study objective Hydroxocobalamin is a Food and Drug Administration–approved antidote for cyanide poisoning. Cobinamide is a potential antidote that contains 2 cyanide-binding sites. To our knowledge, no study has directly compared hydroxocobalamin with cobinamide in a severe, cyanide-toxic large-animal model. Our objective is to compare the time to return of spontaneous breathing in swine with acute cyanide-induced apnea treated with intravenous hydroxocobalamin, intravenous cobinamide, or saline solution (control). Methods Thirty-three swine (45 to 55 kg) were intubated, anesthetized, and instrumented (continuous mean arterial pressure and cardiac output monitoring). Anesthesia was adjusted to allow spontaneous breathing with FiO2 of 21% during the experiment. Cyanide was continuously infused intravenously until apnea occurred and lasted for 1 minute (time zero). Animals were then randomly assigned to receive intravenous hydroxocobalamin (65 mg/kg), cobinamide (12.5 mg/kg), or saline solution and monitored for 60 minutes. A sample size of 11 animals per group was selected according to obtaining a power of 80%, an α of .05, and an SD of 0.17 in mean time to detect a 20% difference in time to spontaneous breathing. We assessed differences in time to death among groups, using Kaplan-Meier estimation methods, and compared serum lactate, blood pH, cardiac output, mean arterial pressure, respiratory rate, and minute ventilation time curves with repeated-measures ANOVA. Results Baseline weights and vital signs were similar among groups. The time to apnea and cyanide dose required to achieve apnea were similar. At time zero, mean cyanide blood and lactate concentrations and reduction in mean arterial pressure from baseline were similar. In the saline solution group, 2 of 11 animals survived compared with 10 of 11 in the hydroxocobalamin and cobinamide groups (P<.001 between the 2 treated groups and the saline solution group). Time to return of spontaneous breathing after antidote was similar between hydroxocobalamin and cobinamide (1 minute 48 seconds versus 1 minute 49 seconds, respectively). Blood cyanide concentrations became undetectable at the end of the study in both antidote-treated groups, and no statistically significant differences were detected between the 2 groups for mean arterial pressure, cardiac output, respiratory rate, lactate, or pH. Conclusion Both hydroxocobalamin and cobinamide rescued severely cyanide-poisoned swine from apnea in the absence of assisted ventilation. The dose of cobinamide was one fifth that of hydroxocobalamin.

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“…A group of European experts has recently acknowledged hydroxocobalamin as a valid empiric treatment for fire smoke victims [7]. For cyanide salt intoxication, as it occurred in present case, Thompson et al, [8] reviewed the available pharmacological data on hydroxycobalamin and concluded that it was an effective antidote.…”

Section: Discussionmentioning

confidence: 99%

Pink skin, urine and effluent fluid after cyanide poisoning

Debord¹,

Bourdin²,

Stoian³

et al. 2013

J Med Disord

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We are reporting a fatal case of cyanide intoxication due to voluntary ingestion treated by hydroxycobalamin as antidote. Twelve hours after ICU admission abnormal pink colored skin and urines were observed. The effluent fluid removed during the continuous veno-venous hemofiltration treatment also exhibited pink colour. Even though pink coloured skin and urines is a well-known side-effect of the hydroxycobalamin use as an antidote for cyanide, such an abnormal colour of the effluent fluid has not been previously reported. Contrary to what has been described with the haemodialysis machines whose functioning may be impaired by hydroxycobalamin, the device used to perform continuous renal replacement therapy has worked properly in present case. Therefore, continuous renal replacement therapy should be the first choice method if needed in this setting.

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Hydroxocobalamin in cyanide poisoning

Cited by 80 publications

References 64 publications

The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics

The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics

Intravenous Cobinamide Versus Hydroxocobalamin for Acute Treatment of Severe Cyanide Poisoning in a Swine (Sus scrofa) Model

Pink skin, urine and effluent fluid after cyanide poisoning

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