Efficacy Of Hydroxocobalamin Research Articles

Fire smoke inhalation and cardiac disorders—Efficacy of hydroxocobalamin: Preliminary results

Fire smoke inhalation and cardiac disorders—Efficacy of hydroxocobalamin: Preliminary results

Role of Hydroxocobalamin in Acute Cyanide Poisoning

To review the recently approved cyanide antidote, hydroxocobalamin, and describe its role in therapy. Relevant publications were identified through a systematic search of PubMed using the MeSH terms and key words hydroxocobalamin and cyanide. This search was then limited to human studies published since 2000. Systematic searches were conducted through January 2008. References from identified articles were reviewed for additional pertinent human studies. The literature search retrieved 7 studies on the safety and/or efficacy of hydroxocobalamin in humans. Four new studies were identified by the search and 3 studies were identified from the references. Studies of antidote efficacy in humans are ethically and logistically difficult. A preclinical study demonstrated that intravenous doses of hydroxocobalamin 5 g are well tolerated by volunteer subjects. Hydroxocobalamin has been shown to reduce cyanide concentrations in controlled studies of nitroprusside therapy and in heavy smokers. A retrospective study of 14 acute cyanide poisonings also demonstrated hydroxocobalamin's safety and efficacy. Two studies examining hydroxocobalamin for smoke inhalation-associated cyanide poisoning indicated a possible benefit, but they are insufficient to establish definitive criteria for use in this setting. Randomized controlled trials of hydroxocobalamin and traditional cyanide antidotes (nitrites/thiosulfate) are lacking. Cyanide poisoning can rapidly cause death. Having an effective antidote readily available is essential for facilities that provide emergency care. In cases of cyanide ingestion, both the nitrite/thiosulfate combination and hydroxocobalamin are effective antidotes. Hydroxocobalamin offers an improved safety profile for children and pregnant women. Hydroxocobalamin also appears to have a better safety profile in the setting of cyanide poisoning in conjunction with smoke inhalation. However, current data are insufficient to recommend the empiric administration of hydroxocobalamin to all victims of smoke inhalation.

Efficacy of Hydroxocobalamin for the Treatment of Acute Cyanide Poisoning in Adult Beagle Dogs

Introduction. The efficacy of hydroxocobalamin for acute cyanide poisoning was compared with that of saline vehicle in dogs. Methods. Anesthetized adult beagle dogs were administered potassium cyanide (0.4 mg/kg/min, IV) until 3 min after the onset of apnea. Hydroxocobalamin (75 mg/kg [n = 19] or 150 mg/kg [n = 18], IV) or saline vehicle [n = 17] was then infused over 7.5 min while animals were ventilated with 100% oxygen, which was stopped after 15 min. Results. In vehicle-treated animals cyanide produced deterioration that culminated in a moribund state requiring euthanasia within 4 h in 10 of 17 animals and in neurological deficits necessitating euthanasia within 2–4 d in an additional 4 animals (mortality rate 82%). Survival through 14 d was observed in 15 of 19 animals administered hydroxocobalamin 75 mg/kg (mortality rate 21%), and 18 of 18 administered hydroxocobalamin 150 mg/kg (mortality rate 0%). Conclusion. Hydroxocobalamin reversed cyanide toxicity and reduced mortality in a canine model.

Antagonism of the Lethal Effects of Cyanide by a Synthetic Water-Soluble Cobalt(III) Porphyrin Compound

Antagonism of the Lethal Effects of Cyanide by a Synthetic Water-Soluble Cobalt(III) Porphyrin Compound. McGuinn, W. D., Baxter, L., Pei, L., Petrikovics, I., Cannon, E. P., and Way, J. L., (1994). Fundam. Appl. Toxicol. 23, 76-80.Efficacy of hydroxocobalamin (vitamin B12) as a cyanide antidote is limited by its high molecular weight (1355 g/mol) and by the competitive binding of the cobalamin dimethylbenzimidazole. The present study describes experiments with a lower molecular weight cobalt porphyrin that has a high affinity for cyanide, Co(III)-5, 10, 15, 20-tetrakis(4-sulfonatophenyl) porphyrin (CoTPPS), which was prepared by the method of Herrmann et al. (1978). CoTPPS was synthesized and its efficacy as an antidote to the lethal effects of cyanide either alone or in various combinations with NaNO2 and/or Na2S2O3 was determined. The LD50 value for CoTPPS was found to be 334 mg/kg. These studies were conducted using the CoTPPS LD01, 200 mg/kg. The cyanide antagonists NaNO2 (0.1 g/kg. sc), Na2S2O3 (1.0 g/kg, ip), and CoTPPS (0.2 g/kg, ip) were administered at 45, 15, and 10 min respectively prior to graded doses of KCN (sc). The LD50 values for KCN in male Swiss-Webster mice were calculated by probit analysis at the 95% confidence level and the various treatments were compared by potency ratios. These results indicated that the administration of CoTPPS alone protects against the lethal effects of cyanide. Moreover, CoTPPS adds to the protection provided by Na2S2O3 and/or NaNO2. Efficacy of this antidote is probably related to the binding equilibrium between CoTPPS and cyanide.

Use of vitamin B12 in the treatment and prevention of nitroprusside-induced cyanide toxicity.

To review the mechanism of action, safety, and efficacy of hydroxocobalamin in the treatment and prevention of nitroprusside-induced cyanide toxicity. English and foreign-language journal articles and reference texts identified from Index Medicus. Both animal and human studies were included. High-dose or prolonged therapy with nitroprusside in patients with hepatic or renal dysfunction increases the risk for nitroprusside-induced cyanide or thiocyanate toxicity, respectively. Hydroxocobalamin has been shown to significantly reduce RBC and plasma cyanide concentrations in animals and surgical patients without producing clinically important adverse effects or toxic metabolites. Thiosulfate infusions also decrease cyanide toxicity but can cause accumulation of thiocyanate resulting in clinical toxicity. Cyanocobalamin cannot effectively remove cyanide due to poor binding. Hydroxocobalamin is a safe and effective agent in the prevention and treatment of nitroprusside-induced cyanide toxicity. Prolonged or high-dose infusions of nitroprusside should be minimized in critically ill patients, especially if hepatic and/or renal dysfunction is present.

In Vitro Demonstration of the Antidotal Efficacy of Hydroxocobalamin in Cyanide Poisoning

The effects of sodium cyanide (1 mM) and the antidotal action of hydroxocobalamin (1 mM) were studied on rat cardiac papillary muscle. A 10-min period of exposure to cyanide induced a marked decrease in inotropy as shown by a decrease in the maximum unloaded shortening velocity (Vmax: 64 +/- 11% of precyanide values, p <0.01) and active isometric force (AF/s: 35 +/- 13%, p <0.01). The impairment of contraction-relaxation coupling under low load and the nearly complete disappearance of the load sensitivity of relaxation suggested a decrease in sarcoplasmic reticulum function. The proportional acceleration in isometric relaxation suggested a decrease in myofilament calcium sensitivity. There was a nearly complete recovery from cyanide poisoning after 5 min of exposure to hydroxocobalamin, whereas in a control group receiving cyanide alone, the mechanical parameters remained unchanged or were further impaired. The effects of hydroxocobalamin developed very quickly, beat to beat. The main toxic target of cyanide is brain and heart cytochrome oxidase, and brain damage appears only a few minutes after the onset of anoxia. Because hydroxocobalamin is a rapid and powerful antidote, it may be useful in the treatment of acute cyanide poisoning.

Hydroxocobalamin therapy of cyanide intoxication in guinea pigs.

The efficacy of hydroxocobalamin (vitamin B12a) as a specific, nontoxic antidote in acute cyanide poisoning was tested. Guinea pigs receiving lethal intravenous NaCN injections were treated with either vitamin B12a or saline solution. There was a statistically significant antidotal effect of the vitamin. No toxic effect was observed with large doses of the vitamin.