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Results for “Hydroxocobalamin”

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At least 19 recordsLinked to original sources
PubMed1995

Simultaneous determination of hydroxocobalamin and its cyanide complex cyanocobalamin in human plasma by high-performance liquid chromatography. Application to pharmacokinetic studies after high-dose hydroxocobalamin as an antidote for severe cyanide poisoning.

Hydroxocobalamin (OHCbl) is a powerful antidote for cyanide poisoning, via the formation of non-toxic cyanocobalamin (CNCbl). Plasmatic cobalamins were measured at 361 nm, after enrichment and purification on a short C18 precolumn (1% acetic acid; 1 ml min-1; 2 min), by back-flush elution on a C18 ODS-2 column [0.1 M sodium dihydrogenphosphate-methanol (63:27, v/v) (pH 4.0); 0.80 ml min-1]. The precision was 3.21 and 3.54% for 10 microM OHCbl and CNCbl, respectively. The method was used to study the pharmacokinetics of OHCbl and the formed CNCbl in severely poisoned patients.

Antidotes↗
PubMed2006

Nitric oxide scavenging by hydroxocobalamin may account for its hemodynamic profile.

BACKGROUND: Antidotal doses of hydroxocobalamin are associated with transient increases in blood pressure in some animals and humans. These studies in anesthetized rabbits were undertaken to explore the possible mechanisms underlying the hemodynamic effects of hydroxocobalamin by investigating 1) possible hemodynamic effects of cyanocobalamin, which is formed on a molar-to-molar basis when hydroxocobalamin binds cyanide, and 2) the interference of hydroxocobalamin with the endothelial nitric oxide system. METHODS: Study 1 investigated the hemodynamic effects of cyanocobalamin. This study included two treatment arms: 1) cyanocobalamin (75 mg/kg, IV) followed by saline (n = 7) and 2) saline followed by cyanocobalamin (n = 7). Study 2 assessed the hemodynamic effects of hydroxocobalamin (75 mg/kg, IV) in the presence and absence of the nitric oxide synthase inhibitor L-Nomega-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg, IV). Nitric oxide synthase inhibition itself increases blood pressure. Thus, as part of Study 2, the hemodynamic effects of hydroxocobalamin were also investigated in the presence of an equipressor dose of angiotensin II (ANGII; 0.05 microg/kg/min, IV) in order to determine whether elevated blood pressure per se could interfere with hydroxocobalamin's hemodynamic effects. This study included six treatment arms (designated as first treatment + second treatment): saline + saline (n = 5), L-NAME + saline (n = 7), saline + hydroxocobalamin (n = 7), L-NAME + hydroxocobalamin (n = 7), ANGII + hydroxocobalamin (n = 7), and ANGII + saline (n = 7). RESULTS: In Study 1, the effects of cyanocobalamin on hemodynamic parameters were indistinguishable from those of saline. In Study 2, hydroxocobalamin infusion was associated with moderate hemodynamic effects, including an increase in systemic vascular resistance, an increase in blood pressure, and a decrease in cardiac output. Administration of L-NAME abolished the effects of hydroxocobalamin on all hemodynamic parameters. ANGII at a dose producing a pressor response comparable to that of L-NAME did not influence the hydroxocobalamin-associated hemodynamic changes. CONCLUSION: These studies in anesthetized rabbits demonstrate that the moderate pressor effect of hydroxocobalamin is not related to the formation of cyanocobalamin but is very likely related to the scavenging of nitric oxide by hydroxocobalamin.

Animals↗
PubMed2006

Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study.

INTRODUCTION: This randomized, double-blind, placebo-controlled, ascending-dose study was conducted in healthy volunteers to evaluate the safety of the investigational cyanide antidote hydroxocobalamin. METHODS: Four ascending dosing groups received intravenous doses of 2.5, 5, 7.5 or 10 g hydroxocobalamin over 7.5 to 30 minutes at a constant infusion rate. Volunteers (n = 136) randomized 3:1 to receive hydroxocobalamin or placebo underwent a 4-day in-house observation after infusion on Day 1 and follow-up visits on Days 8, 15, and 28. RESULTS: The most common drug-related adverse events were asymptomatic and self-limiting chromaturia and reddening of the skin, which are attributed to the red color of hydroxocobalamin. Other adverse events included pustular/papular rash, headache, erythema at the injection site, decrease in lymphocyte percentage, nausea, pruritus, chest discomfort, and dysphagia. Hydroxocobalamin was associated with an increase in blood pressure in some volunteers. Blood pressure changes peaked toward the end of hydroxocobalamin infusion and typically returned to baseline levels by 4 hours postinfusion. Maximum mean changes from baseline in systolic blood pressure ranged from 22.6 to 27.0 mmHg across hydroxocobalamin doses compared with 0.2 to 6.7 mmHg in the corresponding placebo groups. Maximum mean change from baseline in diastolic blood pressure ranged from 14.3 to 25.4 mmHg across hydroxocobalamin doses compared with -3.0 to 3.8 mmHg in the corresponding placebo groups. Two allergic reactions that occurred within minutes after start of the 5- and 10-g hydroxocobalamin infusions were successfully managed with dexamethasone and/or dimethindene maleate. CONCLUSION: Timely intervention for acute cyanide poisoning could entail administration of an antidote in the prehospital setting based on a presumptive diagnosis. Results of this placebo-controlled study in healthy volunteers corroborate previous studies and French postmarketing experience in cyanide-exposed patients in suggesting that the safety profile of hydroxocobalamin is consistent with prehospital or hospital use.

Adolescent↗
PubMed1996

Hydroxocobalamin vs cobalt toxicity on rat cardiac and diaphragmatic muscles.

BACKGROUND: Hydroxocobalamin has been shown to be a rapid and powerful antidote in acute cyanide poisoning and to prevent cyanide poisoning during sodium nitroprusside administration. This cobalt-containing compound has been shown to be devoid of significant immediate side effects during acute administration. However, its potential delayed toxicity related to cobalt accumulation in tissue remains unknown. Therefore, we evaluated the toxicity of hydroxocobalamin as compared with that of cobalt salts on rat cardiac and diaphragmatic muscles. METHODS: For a 21-day period, rats were treated intraperitoneally with either hydroxocobalamin (70 mg kg-1 per day, n = 14), cobalt chloride hexahydrate (12 mg kg-1 per day, n = 14) or saline (n = 10). Hydroxocobalamin and cobalt chloride groups received equimolar doses of cobalt. We studied: (1) the mechanical properties of isolated left ventricular papillary muscles and diaphragmatic strips, (2) the cardiac and diaphragmatic cobalt tissue concentrations, and (3) the myocardial histological aspect. RESULTS: During the study period, no significant increase in body weight was noted in the cobalt-treated group (-4 +/- 1%), which was in contrast to the hydroxocobalamin-treated group (+21 +/- 2%) and the saline-treated group (22 +/- 2%). Compared with controls, the mechanical properties of cardiac and diaphragmatic muscles were unchanged after either hydroxocobalamin or cobalt salt treatments, and myocardial histological characteristics were similar in all groups. Conversely, large amounts of cobalt deposit were observed in the cobalt-treated group in both the diaphragm (41.90 +/- 16.30 vs 0.70 +/- 0.40 mu mol mu g-1 in the control group, P < 0.001) and the myocardium (16.90 +/- 6.40 vs 0.14 +/- 0.01 mu mol mu g-1 in the control group, P < 0.001). After hydroxocobalamin administration, cobalt concentrations were significantly lower in the diaphragm (25.10 +/- 16.50 mu mol mu g-1, P < 0.001 vs cobalt-treated group) and the myocardium (4.50 +/- 1.20 mu mol mu g, P < 0.001 vs cobalt-treated group). CONCLUSION: These results indicate that repeated administration of hydroxocobalamin was devoid of significant diaphragmatic and cardiac muscle toxicity and therefore remains a safe antidote for acute cyanide poisoning.

Analysis of Variance↗
PubMed2006

Prehospital administration of hydroxocobalamin for smoke inhalation-associated cyanide poisoning: 8 years of experience in the Paris Fire Brigade.

INTRODUCTION: This article reports the results of a retrospective study of 8 years of experience of the Paris Fire Brigade with the prehospital use of hydroxocobalamin. METHODS: The head physician at the Paris Fire Brigade extracted and summarized data from standardized forms completed at the fire scene and, when available, hospital reports to assess survival status and clinical parameters associated with the use of hydroxocobalamin for each patient who received it for smoke inhalation-associated cyanide poisoning from 1995 to 2003. RESULTS: Of the 101 patients administered hydroxocobalamin, 30 survived, 42 died (17 at the fire scene and 25 at the intensive-care unit), and survival status was not known in the remaining 29 patients. Among the 72 patients for whom survival status was known, survival rate was 41.7% after the administration of hydroxocobalamin. Of the 38 patients found in cardiac arrest, 21 had a return of spontaneous circulation during prehospital care. Of the 12 patients who were initially hemodynamically unstable (systolic blood pressure 0 to < or =90 mmHg), 9 recovered systolic blood pressure an average of 30.6 minutes after the start of hydroxocobalamin infusion. Among nonsedated patients in the sample as a whole (n = 52), mean (SD) Glasgow coma scale score improved from 7.9 (5.4) initially to 8.5 (5.7) after administration of hydroxocobalamin. Among nonsedated patients who were initially neurologically impaired (n = 18), Glasgow coma scale score improved in 9 patients, did not change in 8 patients, and worsened in 1 patient. Two adverse events--red or pink coloration of urine or skin (n = 5) and cutaneous rash (n = 1)--were assessed as being possibly related to hydroxocobalamin. CONCLUSION: Hydroxocobalamin has a risk:benefit ratio rendering it suitable for prehospital use in the management of acute cyanide poisoning caused by smoke inhalation.

Adult↗
PubMed1995

Relation of blood cyanide to plasma cyanocobalamin concentration after a fixed dose of hydroxocobalamin in cyanide poisoning.

Hydroxocobalamin combines with cyanide to form cyanocobalamin. We hypothesised that the amount of cyanocobalamin formed after a fixed dose of hydroxocobalamin given for cyanide poisoning would correlate with initial blood cyanide concentration. We determined blood cyanide concentration in 12 patients exposed to residential fires, and compared this with markers of the amount of cyanocobalamin formed after treatment with 5 g intravenous hydroxocobalamin. All relationships were highly correlated (r2 0.79-0.95), for the whole group, and there appeared to be an almost linear relationship for the 9 patients with initial cyanide concentration below 40 mumol/L. Above this concentration, no further cyanocobalamin was formed from a single 5 g dose of hydroxocobalamin. In one patient with initial blood cyanide concentration of 96 mumol/L, however, plasma cyanocobalamin concentration approximately doubled after a second 5 g dose of hydroxocobalamin. 5 g of hydroxocobalamin appears capable of binding all available cyanide ions for blood cyanide concentrations up to about 40 mumol/L. Beyond this, more hydroxocobalamin must be given for remaining cyanide ions to be bound. This information will allow clinicians to use rapidly measurable plasma cyanocobalamin concentrations to gauge severity of exposure and evaluate adequacy of treatment.

Adult↗