hydroxocobalamin and Poisoning

The importance of cyanide toxicity as a component of inhalational injury in patients with burns is increasingly being recognised, and its prompt recognition and management is vital for optimising burns survival. The evidence base for the use of cyanide antidotes is limited by a lack of randomised controlled trials in humans, and in addition consideration must be given to the concomitant pathophysiological processes in patients with burns when interpreting the literature. We present a literature review of the evidence base for cyanide antidotes with interpretation in the context of patients with burns. We conclude that hydroxycobalamin should be utilised as the first-line antidote of choice in patients with burns with inhalational injury where features consistent with cyanide toxicity are present.

Topics: Adenosine; Amyl Nitrite; Burns; Chelating Agents; Cyanides; Edetic Acid; Humans; Hydroxocobalamin; Hyperbaric Oxygenation; Oxygen Inhalation Therapy; Poisoning; Pteridines; Smoke Inhalation Injury; Sodium Nitrite; Thiosulfates

Topics: Antidotes; Blood Chemical Analysis; Carbon Monoxide; Emergency Medical Services; Emergency Service, Hospital; Female; Fires; Follow-Up Studies; Humans; Hydrogen Cyanide; Hydroxocobalamin; Middle Aged; Poisoning; Risk Assessment; Smoke Inhalation Injury; Treatment Outcome; Vital Signs

On theoretical grounds, hydroxocobalamin is an attractive antidote for cyanide poisoning as cobalt compounds have the ability to bind and detoxify cyanide. This paper reviews the pharmacokinetic and pharmacodynamic aspects of hydroxocobalamin, its efficacy in human cyanide poisoning and its adverse effects.. PubMed was searched for the period 1952 to April 2012. A total of 71 papers were identified in this way; and none was excluded. PHARMACOKINETICS AND PHARMACODYNAMICS: Pharmacokinetic studies in dogs and humans suggest a two-compartment model, with first order elimination kinetics. Pharmacodynamic studies in animals suggest that hydroxocobalamin would be a satisfactory antidote for human cyanide poisoning. EFFICACY IN HUMAN POISONING: There is limited evidence that hydroxocobalamin alone is effective in severe poisoning by cyanide salts. The evidence for the efficacy of hydroxocobalamin in smoke inhalation is complicated by lack of evidence for the importance of cyanide exposure in fires and the effects of other chemicals as well as confounding effects of other therapeutic measures, including hyperbaric oxygen. Evidence that hydroxocobalamin is effective in poisoning due to hydrogen cyanide alone is lacking; extrapolation of efficacy from poisoning by ingested cyanide salts may not be valid. The rate of absorption may be greater with inhaled hydrogen cyanide and the recommended slow intravenous administration of hydroxocobalamin may severely limit its clinical effectiveness in these circumstances.. Both animal and human data suggest that hydroxocobalamin is lacking in clinically significant adverse effects. However, in one human volunteer study, delayed but prolonged rashes were observed in one-sixth of subjects, appearing 7 to 25 days after administration of 5 g or more of hydroxocobalamin. Rare adverse effects have included dyspnoea, facial oedema, and urticaria.. Limited data on human poisonings with cyanide salts suggest that hydroxocobalamin is an effective antidote; data from smoke inhalation are less clear-cut. Although clinically important reactions to hydroxocobalamin have not been seen, some, non-life threatening, adverse reactions can occur.

Topics: Animals; Antidotes; Cyanides; Dogs; Drug Therapy, Combination; Female; Humans; Hydroxocobalamin; Inhalation Exposure; Male; Poisoning; PubMed; Rats; Smoke; Treatment Outcome

Poisonings, adverse drug effects, and envenomations continue to be commonly encountered. Patients often present critically ill and warrant ICU admission. Many other patients who are initially stable have the potential for rapid deterioration and require continuous cardiopulmonary and neurologic monitoring. Given the potential for rapid deterioration, and because patients need continuous monitoring, ICU admission is frequently required. This article is the first of a three-part series to be published in CHEST; it discusses general management, laboratory tests, enhanced elimination, and emerging therapies. The second article will address the management of specific overdoses; the last will cover plants, mushrooms, envenomations, and heavy metals.

Topics: Acid-Base Equilibrium; Acidosis; Fat Emulsions, Intravenous; Humans; Hydroxocobalamin; Intensive Care Units; Naloxone; Narcotic Antagonists; Neuroleptic Malignant Syndrome; Osmolar Concentration; Poisoning; Renal Dialysis; Serotonin Syndrome; Therapeutic Irrigation; Xenobiotics

Topics: Anesthetics, Local; Antidotes; Antivenins; Calcium Channel Blockers; Child, Preschool; Cyanides; Emergency Treatment; Fat Emulsions, Intravenous; Fomepizole; Humans; Hydroxocobalamin; Hypoglycemic Agents; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Insulin; Male; Methanol; Middle Aged; Poison Control Centers; Poisoning; Pyrazoles; Snake Bites; Vitamin B Complex

Topics: Acute Disease; Adult; Aftercare; Amyl Nitrite; Antidotes; Cyanides; Decontamination; Emergency Medical Services; Emergency Nursing; Emergency Treatment; Humans; Hydroxocobalamin; Life Support Care; Male; Nurse's Role; Parkinsonian Disorders; Poisoning; Sodium Nitrite; Suicide, Attempted; Thiosulfates; Triage

Although some antidotes are rarely used, they have an important, potentially life-saving role in the treatment of toxic exposures. The timely and judicious use of an antidote can prevent death and shorten hospitalization as well as reduce the patient's pain and suffering. Although their importance is recognized, sufficient stocking of antidotes remains a problem.

Topics: Animals; Antidotes; Antivenins; Crotalid Venoms; Emergency Treatment; Fomepizole; Glucagon; Humans; Hydroxocobalamin; Octreotide; Physostigmine; Poisoning; Pyrazoles; Snake Bites; Viperidae

The United States is under the constant threat of a mass casualty cyanide disaster from industrial accidents, hazardous material transportation incidents, and deliberate terrorist attacks. The current readiness for cyanide disaster by the emergency medical system in the United States is abysmal. We, as a nation, are simply not prepared for a significant cyanide-related event. The standard of care for cyanide intoxication is the cyanide antidote kit, which is based on the use of nitrites to induce methemoglobinemia. This kit is both expensive and ill suited for out-of-hospital use. It also has its own inherent toxicity that prevents rapid administration. Furthermore, our hospitals frequently fail to stock this life-saving antidote or decline to stock more than one. Hydroxocobalamin is well recognized as an efficacious, safe, and easily administered cyanide antidote. Because of its extremely low adverse effect profile, it is ideal for out-of-hospital use in suspected cyanide intoxication. To effectively prepare for a cyanide disaster, the United States must investigate, adopt, manufacture, and stockpile hydroxocobalamin to prevent needless morbidity and mortality.

Topics: Accidents, Occupational; Amyl Nitrite; Antidotes; Chemical Warfare; Cyanides; Disaster Planning; Emergency Medical Services; Emergency Treatment; Hazardous Substances; Humans; Hydroxocobalamin; Needs Assessment; Poisoning; Public Health Practice; Sodium Nitrite; Terrorism; Thiosulfates; Transportation; United States

Poisonings are a common problem. In 1995, over 2 million exposures were reported to American poison information centres alone. The majority of poisoning exposures can be treated without major therapeutic intervention. If therapy is indicated, it is usually in the form of gastrointestinal decontamination with activated charcoal, to prevent absorption of the toxin and the subsequent toxicity that may occur. In a limited number of cases, more aggressive life-support measures may be necessary to treat the adverse effects of poisons. Occasionally, that intervention may include the use of pharmacological antagonists, more commonly referred to as antidotes. According to the American Association of Poison Control Centers, the most commonly used antidotes are acetylcysteine, naloxone, atropine, deferoxamine (desferrioxamine) and antivenins. Overall, 17 antidotes account for 99% of all antidote use and those agents are reviewed in this article. With the exception of naloxone, most antidotes have pharmacological effects that are independent of their inherent antidotal properties. Therefore, antidotes should be used judiciously because their pharmacological properties may exacerbate pre-existing toxicity and only in rare circumstances are they used prophylactically. Some antidotes, such as digoxin-specific antigen binding fragments (digoxin immune Fab), are very expensive, and both the risk: benefit ratio and the associated cost should be considered before the antidote is administered. The principle aims are to "treat the patient, not the poison' and to do no harm to the patient. Antidotes should be used only when they are indicated and may help a patient.

Topics: Acetylcysteine; Antidotes; Antivenins; Atropine; Deferoxamine; Flumazenil; Humans; Hydroxocobalamin; Naloxone; Physostigmine; Poisoning; Succimer

Cyanide is a potent and rapidly-acting asphyxiant which prevents tissue utilization of oxygen by inhibition of the cellular respiratory enzyme, cytochrome oxidase. Inhalation or ingestion of cyanide produces reactions within a few seconds and death within minutes. Cyanide toxicity of dietary origin has been implicated in acute animal deaths and as major etiologic factors in toxic ataxic neuropathy in man and as a cause of vision failure in humans suffering from tobacco amblyopia and leber's hereditary optic atrophy. Diagnosis of cyanide toxicity may be confirmed by a variety of laboratory procedures, but accurate assay is essential for proper conclusions from analysis of animal tissues several hours after death or from human samples in instances of chronic dietary exposure. Biological detoxification of cyanide is available through several routes, and the application of sodium nitrite with sodium thiosulfate or administration of methylene blue are effective treatment procedure. The environmental availability of cyanide in its various forms necessitates an understanding of its pathophysiology and responsible management of hazardous situations.

Topics: Absorption; Animal Husbandry; Animals; Chelating Agents; Chemical Phenomena; Chemistry; Cyanides; Electron Transport Complex IV; Environmental Pollutants; Humans; Hydroxocobalamin; Hypoxia; Inactivation, Metabolic; Poisoning; Postmortem Changes; Sodium Nitrite; Thiosulfates

Hydroxocobalamin (OHCob) is an antidote for cyanide poisoning in patients rescued from house fires and is known to cause interference with certain laboratory tests. Consensus is lacking on the extent of this interference and on how to handle these samples. The objectives of this study were to characterize OHCob interference across a wide range of laboratory tests and to develop protocols for identifying and reporting these samples.. Patient plasma samples (n = 5) were spiked with OHCob (1.5 mg/mL) and compared to controls without this drug. A series of analytes were measured using chemistry, urinalysis, coagulation, hematology, and blood gas instruments. Dose-response testing was performed on a subset of assays that showed interferences ≥10%.. Of the 77 analytes evaluated, 27 (35%) showed interference from OHCob, with chemistry and coagulation analytes showing the greatest effects. Of those affected, 22 analytes had a positive interference, whereas 5 analytes had negative interference. Dose-response studies showed dose-dependent increases and/or decreases consistent with initial spiking studies. Although red in colour, plasma samples with OHCob did not trigger hemolysis index flags, necessitating a special sample identification and reporting protocol.. OHCob had significant effects on several analytes across different instruments. These findings led to the development of special sample handling and reporting protocols to identify OHCob samples and ensure only accurate results are released. It is vital for emergency departments to document and notify their laboratories whenever blood samples from these patients are drawn.

Topics: Antidotes; Blood Chemical Analysis; Female; Humans; Hydroxocobalamin; Male; Poisoning; Potassium Cyanide

To assess the relationship between blood pressure changes following infusion of antidotal doses of hydroxocobalamin and plasma concentrations of total and free cobalamins-(III).. Independent groups of healthy volunteers received single intravenous doses of 2.5, 5, 7.5, or 10 g hydroxocobalamin over 7.5 to 30 minutes.. In the pharmacokinetic population (n = 41), hydroxocobalamin caused short-lived mean blood pressure increases. Blood pressure increased shortly after initiation of infusion and returned nearly to baseline by 4 hours post-infusion. The time course of blood pressure changes coincided with that of changes in plasma total and free cobalamins-(III). Change in mean arterial pressure (MAP) was strongly correlated with plasma area-under-the-concentration-time curves (AUCs) of total and free cobalamins-(III) during infusion (r > 0.7) but not through 24 hours post-infusion (r < or = 0.36).. The short-lived increase in mean blood pressure during administration of antidotal doses of hydroxocobalamin is closely linked to initial exposure to total and free cobalamins-(III).

Topics: Adult; Antidotes; Area Under Curve; Blood Pressure; Dose-Response Relationship, Drug; Female; Humans; Hydroxocobalamin; Infusions, Intravenous; Male; Middle Aged; Poisoning; Time Factors; Vitamin B 12

This randomized, double-blind, placebo-controlled, ascending-dose study was conducted in healthy volunteers to evaluate the safety of the investigational cyanide antidote hydroxocobalamin.. 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.. 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.. 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.

Topics: Adolescent; Adult; Antidotes; Blood Pressure; Cyanides; Double-Blind Method; Emergency Medical Services; Female; Heart Rate; Humans; Hydroxocobalamin; Infusions, Intravenous; Male; Middle Aged; Pigments, Biological; Poisoning; Skin

Chronic cyanide intoxication of dietary origin and riboflavine deficiency are believed to be major aetiological factors in Nigerian tropical ataxic neuropathy. The results are presented of a double-blind controlled therapeutic trial of combinations of large doses of hydroxocobalamin and cystine as cyanide binding agents together with riboflavine or placebos in Nigerian patients suffering from the tropical ataxic neuropathy. No clinical benefit was demonstrable with any of the treatments.

Topics: Ataxia; Cyanides; Cystine; Deafness; Evaluation Studies as Topic; Female; Humans; Hydroxocobalamin; Male; Middle Aged; Nigeria; Optic Atrophy; Peripheral Nervous System Diseases; Placebos; Poisoning; Riboflavin; Riboflavin Deficiency; Syndrome; Thiocyanates; Vitamin B 12

We quantify the impact of several variables including site of blood draw, delay in measurement, and use of the cyanide antidote hydroxocobalamin on detection of both normal (<2 mmol/L) and elevated (>6 mmol/L) human plasma lactate. An in vivo study assessed effects of venous or arterial origin of blood samples. Two in vitro studies assessed the effect of a 2 h delay in measuring plasma lactate concentrations, as well as the interference of low (100 μmol/L) and high (300 μmmol/L) plasma hydroxocobalamin concentrations on detecting normal and elevated levels of lactate. A relative change of 20% in the measured lactate concentration was considered clinically significant. There was no clinically relevant effect of the site of blood draw on lactate measurements. Plasma lactate concentrations were artificially increased by a delay of 2 h between blood draw and sample measurement. Under conditions where plasma lactate levels were in a normal range, the dose equivalent to 300 μmol/L hydroxocobalamin concentration caused an artificial increase in lactate measurements that could possibly be misinterpreted clinically as an elevation. Under conditions where plasma lactate levels were elevated, as would occur in cases of acute cyanide poisoning, neither the low nor high concentration of hydroxocobalamin caused a clinically relevant change in lactate measurements. Clinicians should be cautious in interpreting lactate concentrations if there has been a significant delay between blood draw and laboratory analysis, or when blood was collected shortly after the completion of hydroxocobalamin administration.

Topics: Antidotes; Arteries; Blood Chemical Analysis; Blood Specimen Collection; Case-Control Studies; Cyanides; Delayed Diagnosis; Humans; Hydroxocobalamin; Lactic Acid; Poisoning; Time Factors; Veins

Topics: Antidotes; Cyanides; Humans; Hydroxocobalamin; Male; Middle Aged; Pigmentation Disorders; Poisoning; Smoke Inhalation Injury

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).. 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.. 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.. 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.

Topics: Animals; Antidotes; Apnea; Cobamides; Cyanides; Disease Models, Animal; Female; Hemodynamics; Hydroxocobalamin; Infusions, Intravenous; Poisoning; Random Allocation; Swine

Hydrogen sulphide (H2S), a chemical hazard in oil and gas production, has recently become a dreadful method of suicide, posing specific risks and challenges for the first responders. Currently, there is no proven effective treatment against H2S poisoning and its severe neurological, respiratory or cardiac after-effects. We have recently described that H2S is present in various compartments, or pools, in the body during sulphide exposure, which have different levels of toxicity. The general goals of our study were to (1) determine the concentrations and kinetics of the various pools of hydrogen sulphide in the blood, i.e., gaseous (CgH2S) versus total sulphide, i.e., reacting with monobromobimane (CMBBH2S), during and following H2S exposure in a small and large mammal and (2) establish the interaction between the pools of H2S and a methemoglobin (MetHb) solution or a high dose of hydroxocobalamin (HyCo). We found that CgH2S during and following H2S infusion was similar in sedated sheep and rats at any given rate of infusion/kg and provoked symptoms, i.e., hyperpnea and apnea, at the same CgH2S. After H2S administration was stopped, CgH2S disappeared within 1 min. CMBBH2S also dropped to 2-3μM, but remained above baseline levels for at least 30 min. Infusion of a MetHb solution during H2S infusion produced an immediate reduction in the free/soluble pool of H2S only, whereas CMBBH2S increased by severalfold. HyCo (70 mg/kg) also decreased the concentrations of free/soluble H2S to almost zero; CgH2S returned to pre-HyCo levels within a maximum of 20 min, if H2S infusion is maintained. These results are discussed in the context of a relevant scenario, wherein antidotes can only be administered after H2S exposure.

Topics: Animals; Antidotes; Female; Gases; Hydrogen Sulfide; Hydroxocobalamin; Male; Methemoglobin; Poisoning; Rats, Sprague-Dawley; Sheep; Sulfides

Pre-hospital administration of hydroxocobalamin (B12a) is used for empiric treatment of cyanide poisoning because cyanide poisoning is difficult to identify and requires immediate treatment. B12a interferes with the accuracy of several blood laboratory tests. This study aimed to explore how B12a affects carboxyhemoglobin (COHb) measurements in human blood at both physiologic and pathologic COHb levels.. Several clinically relevant concentrations of B12a were added to human blood samples containing physiologic (∼ 3%) and pathologic (30% and 50%) COHb levels. We then measured the COHb levels of the samples using two different co-oximeters, the Radiometer ABL 700 and the Rapidpoint 500, and compared to their actual baseline COHb levels.. B12a had minimal effects on the COHb measured at both physiologic and pathologic levels when measured on the Radiometer. In contrast, the Rapidpoint B12a caused a dose-dependent decrease in the COHb measured, especially of pathologic COHb levels (∼ 30 and 50%).. The magnitude of B12a interference on measured COHb is dependent upon the specific co-oximeter used, the actual COHb level and the serum B12a concentration. These errors may potentially influence clinical decision making and thus affect patient outcomes. Our findings emphasize the importance of measuring COHb levels on blood samples collected prior to B12a administration.

Topics: Antidotes; Carboxyhemoglobin; Cyanides; Diagnostic Errors; Humans; Hydroxocobalamin; Osmolar Concentration; Oximetry; Poisoning; Reproducibility of Results; Vitamin B Complex

Hydroxocobalamin is a treatment for cyanide toxicity with few side effects. We report a case of a hemodialysis patient whose treatment was compromised by hydroxocobalamin interference with the blood leak detector.

Topics: Antidotes; Clinical Alarms; Color; Equipment Design; Equipment Failure; Humans; Hydroxocobalamin; Kidney Failure, Chronic; Kidneys, Artificial; Male; Middle Aged; Nitroprusside; Poisoning; Renal Dialysis; Vasodilator Agents

Most fire-related deaths are attributable to smoke inhalation rather than burns. The inhalation of fire smoke, which contains not only carbon monoxide but also a complex mixture of gases, seems to be the major cause of morbidity and mortality in fire victims, mainly in enclosed spaces. Cyanide gas exposure is quite common during smoke inhalation, and cyanide is present in the blood of fire victims in most cases and may play an important role in death by smoke inhalation. Cyanide poisoning may, however, be difficult to diagnose and treat. In these children, hydrogen cyanide seems to be a major source of concern, and the rapid administration of the antidote, hydroxocobalamin, may be critical for these children.European experts recently met to formulate an algorithm for prehospital and hospital management of adult patients with acute cyanide poisoning. Subsequently, a group of European pediatric experts met to evaluate and adopt that algorithm for use in the pediatric population.

Topics: 4-Aminopyridine; Age Factors; Algorithms; Antidotes; Child; Child, Preschool; Cyanides; Disease Management; Disease Susceptibility; Emergencies; Emergency Medical Services; Europe; Fires; Humans; Hydroxocobalamin; Infant; Methemoglobinemia; Poisoning; Smoke; Smoke Inhalation Injury; Sodium Nitrite; Thiosulfates

Topics: Antidotes; Charcoal; Child, Preschool; Coma; Cyanides; Emergency Service, Hospital; Female; Humans; Hydroxocobalamin; Poisoning; Prunus; Seeds; Vitamin B Complex

Here we report the case of a 70-year-old woman who committed suicide by cyanide poisoning. During resuscitation cares, she underwent an antidote treatment by hydroxocobalamin. Postmortem investigations showed marked bright pink discolouration of organs and fluids, and a lethal cyanide blood concentration of 43 mg/L was detected by toxicological investigation. Discolouration of hypostasis and organs has widely been studied in forensic literature. In our case, we interpreted the unusual pink coloration as the result of the presence of hydroxocobalamin. This substance is a known antidote against cyanide poisoning, indicated because of its efficiency and poor adverse effects. However, its main drawback is to interfere with measurements of many routine biochemical parameters. We have tested the potential influence of this molecule in some routine postmortem investigations. The results are discussed.

Topics: Aged; Antidotes; Cerebrospinal Fluid; Cyanides; Dura Mater; Female; Forensic Pathology; Humans; Hydroxocobalamin; Pericardium; Pigmentation Disorders; Pleura; Poisoning; Respiratory Mucosa; Scalp; Suicide; Ureter; Urothelium; Vitreous Body

A patient committed suicide with hydrogen sulfide (H(2)S) by combining two commercial products. The patient was given hydroxocobalamin as an antidote in addition to treatment with cardiopulmonary resuscitation, but died approximately 42 min after his arrival at the hospital. The patient's cause of death was attributed to acute hydrogen sulfide poisoning. Serum concentrations of sulfide before and after administration of hydroxocobalamin were 0.22 and 0.11 μg/mL, respectively; serum concentrations of thiosulfate before and after hydroxocobalamin administration were 0.34 and 0.04 μmol/mL, respectively. Hydroxocobalamin is believed to form a complex with H(2)S in detoxification pathways of H(2)S. Although H(2)S is rapidly metabolized and excreted, the decreased sulfide concentration may be also associated with this complex formation. The decreased sulfide concentration suggests that hydroxocobalamin therapy may be effective for acute H(2)S poisoning. The decreased thiosulfate concentration seems to be associated with formation of a thiosulfate/hydroxocobalamin complex, because hydroxocobalamin can form a complex with thiosulfate. The thiosulfate concentration decreased to a greater extent than did sulfide, suggesting that hydroxocobalamin has a higher affinity for thiosulfate than for H(2)S. Therefore, prompt administration of hydroxocobalamin after H(2)S exposure may be effective for H(2)S poisoning.

Topics: Adult; Air Pollutants; Antidotes; Fatal Outcome; Humans; Hydrogen Sulfide; Hydroxocobalamin; Male; Poisoning; Suicide; Young Adult

Clinical experience with hydroxocobalamin in acute cyanide poisoning via ingestion remains limited. This case concerns a 35-year-old mentally ill woman who consumed more than 20 apricot kernels. Published literature suggests each kernel would have contained cyanide concentrations ranging from 0.122 to 4.09 mg/g (average 2.92 mg/g). On arrival, the woman appeared asymptomatic with a raised pulse rate and slight metabolic acidosis. Forty minutes after admission (approximately 70 min postingestion), the patient experienced headache, nausea and dyspnoea, and was hypotensive, hypoxic and tachypnoeic. Following treatment with amyl nitrite and sodium thiosulphate, her methaemoglobin level was 10%. This prompted the administration of oxygen, which evoked a slight improvement in her vital signs. Hydroxocobalamin was then administered. After 24 h, she was completely asymptomatic with normalised blood pressure and other haemodynamic parameters. This case reinforces the safety and effectiveness of hydroxocobalamin in acute cyanide poisoning by ingestion.

Topics: Acute Disease; Adult; Female; Hematinics; Humans; Hydrogen Cyanide; Hydroxocobalamin; Poisoning; Prunus; Seeds; Treatment Outcome

Enclosed-space smoke inhalation is the fifth most common cause of all unintentional injury deaths in the United States. Increasingly, cyanide has been recognized as a significant toxicant in many cases of smoke inhalation. However, it cannot be emergently verified. Failure to recognize the possibility of cyanide toxicity may result in inadequate treatment. Findings suggestive cyanide toxicity include: (1) a history of an enclosed-space fire scene in which smoke inhalation was likely; (2) the presence of oropharyngeal soot or carbonaceous expectorations; (3) any alteration of the level of consciousness, and particularly, otherwise inexplicable hypotension (systolic blood pressure ≤90 mmHg in adults). Prehospital studies have demonstrated the feasibility and safety of empiric treatment with hydroxocobalamin for patients with suspected smoke inhalation cyanide toxicity. Although United States Food and Drug Administration (FDA)-approved since 2006, the lack of efficacy data has stymied the routine use of this potentially lifesaving antidote. Based on a literature review and on-site observation of the Paris Fire Brigade, emergency management protocols to guide empiric and early hydroxocobalamin administration in smoke inhalation victims with high-risk presentations are proposed.

Topics: Emergency Medical Services; Emergency Treatment; Fires; Humans; Hydrogen Cyanide; Hydroxocobalamin; Poisoning; Smoke Inhalation Injury; United States

To report diagnostic, clinical and therapeutic aspects of cyanide intoxication resulting from ingestion of cyanogenic glucoside-containing apricot seeds.. Thirteen patients admitted to the Pediatric Intensive Care Unit (PICU) of Erciyes University between 2005 and 2009 with cyanide intoxication associated with ingestion of apricot seeds were reviewed retrospectively.. Of the 13 patients, four were male. The mean time of onset of symptoms was 60 minutes (range 20 minutes to 3 hours). On admission, all patients underwent gastric lavage and received activated charcoal. In addition to signs of mild poisoning related to cyanide intoxication, there was severe intoxication requiring mechanical ventilation (in four cases), hypotension (in two), coma (in two) and convulsions (in one). Metabolic acidosis (lactic acidosis) was detected in nine patients and these were treated with sodium bicarbonate. Hyperglycaemia occurred in nine patients and blood glucose levels normalised spontaneously in six but three required insulin therapy for 3-6 hours. Six patients received antidote treatment: high-dose hydroxocobalamin in four and two were treated with a cyanide antidote kit in addition to high-dose hydroxocobalamin. One patient required anticonvulsive therapy. All patients recovered and were discharged from the PICU within a mean (SD, range) 3.1 (1.7, 2-6) days.. Cyanide poisoning associated with ingestion of apricot seeds is an important poison in children, many of whom require intensive care.

Topics: Acidosis; Antidotes; Charcoal; Child; Child, Preschool; Coma; Cyanides; Eating; Female; Gastric Lavage; Hematinics; Humans; Hydroxocobalamin; Hyperglycemia; Insulin; Male; Poisoning; Prunus; Respiratory Insufficiency; Retrospective Studies; Seeds; Seizures; Sodium Bicarbonate; Turkey

Topics: Cyanides; Female; Hematinics; Humans; Hydroxocobalamin; Middle Aged; Photography; Poisoning; Skin Pigmentation; Smoke Inhalation Injury

Currently, no reliable noninvasive methods exist for monitoring the severity of in vivo cyanide (CN) toxicity, treatment, and resulting physiological changes. We developed a broadband diffuse optical spectroscopy (DOS) system to measure bulk tissue absorption and scattering. DOS was used to optically monitor CN toxicity and treatment with sodium nitrite (NaNO2). To perform experiments, the DOS probe was placed on the hind leg of rabbits. A sodium CN solution was infused intravenously. DOS and concurrent physiologic measurements were obtained. After completion of CN infusion, NaNO2 was infused to induce methemoglobinemia (MetHb). During infusion of CN, blood gas measurements showed an increase in venous partial pressure of oxygen (pO2), and following reversal, venous pO2 values decreased. DOS measurements demonstrated corresponding changes in hemoglobin oxygenation states and redox states of cytochrome-c oxidase (CcO) during CN infusion and NaNO2 treatment. Therefore, DOS enables detection and monitoring of CN toxicity and treatment with NaNO2.

Topics: Animals; Blood Gas Analysis; Electron Transport Complex IV; Feasibility Studies; Hematinics; Hemoglobins; Hydroxocobalamin; Indicators and Reagents; Male; Methemoglobin; Models, Animal; Oximetry; Oxyhemoglobins; Poisoning; Potassium Cyanide; Rabbits; Sodium Nitrite; Spectrophotometry, Infrared; Spectrum Analysis; Statistics as Topic; Toxicity Tests, Acute

Topics: Antidotes; Chemical Warfare Agents; Cyanides; Humans; Hydroxocobalamin; Poisoning

Topics: Animals; Antidotes; Carbon Monoxide Poisoning; Humans; Hydrogen Cyanide; Hydroxocobalamin; Poisoning; Smoke Inhalation Injury

Topics: Animals; Antidotes; Cyanides; Humans; Hydroxocobalamin; Poisoning; Thiosulfates

Sodium azide poisonings occur very rarely. The mechanism of sodium azide toxic effect has not yet been fully explained. Despite the lack of an explicit procedure for the cases of sodium azide poisonings, in vitro tests and rare case reports suggest that treatment with antidotes for cyanide poisoning victims can be effective. This study describes two cases of suicidal sodium azide ingestion. Case 1. 30-year-old male ingested ca. 180 mg of sodium azide. On admission to hospital, within 4 hours from poisoning, the man complained of dizziness and anxiety. Physical examination revealed horizontal nystagmus, flapping tremor, HR 135/min. In laboratory tests, higher blood concentration of lactates (3 mmol/l) was detected, as well as lower potassium concentration (3.4 mmol/L) and increased transaminase activity (ALT 74 U/l, AST 90 U/l). Electrocardiographic tests showed a negative T wave in limb lead III. Other results were within normal. As the patient ingested a toxic dose of sodium azide, he was treated according to the therapy prescription for cyanide poisoning (amyl nitrite inhalation followed by intravenous administration of sodium nitrite and sodium thiosulphate). ECG record of the last day of hospitalization (7th day of treatment) showed negative T waves in lead III, V4-V6. He was discharged from hospital in good condition. Case 2.23-year-old male ingested 10 g of sodium azide 1.5 hours prior to admission to hospital. At the beginning, the patient's condition was good, but it changed to critical state within the first hours of hospitalization. He developed a deep coma, respiratory and circulatory insufficiency, metabolic acidosis, cardiac dysrrhythmias and anuria. Cardiac activity monitoring showed alternating tachycardia (140 beats per minute) and bradycardia (48 beats per minute), numerous additional supraventricular and ventricular extrasystoles and sinus dysrrhythmia. Cardiac arrest (asystolia) occurred twice, the second incident with fatal outcome. The patient received supportive therapy, he was also treated according to the therapy prescription for cyanide poisoning. Circulatory disturbances observed in both cases have been described in literature as symptoms of sodium azide poisoning. However, available literature data are scarce and lack systematization, most of them coming from several decades ago. The lack of patient's consent for detailed examination of circulatory system and liver made it impossible to gather further knowledge on the subject. T

Topics: Adult; Antidotes; Arrhythmias, Cardiac; Bradycardia; Clinical Protocols; Dose-Response Relationship, Drug; Electrocardiography; Fatal Outcome; Heart Arrest; Humans; Hydroxocobalamin; Hypokalemia; Lactates; Male; Monitoring, Physiologic; Nitrates; Pentanols; Poisoning; Sodium Azide; Sodium Nitrite; Suicide, Attempted; Thiosulfates; Transaminases; Treatment Outcome

Recently, H(2)S (an environmental toxin) was proposed to induce cytotoxicity not only by inhibiting cytochrome oxidase but also by generating reactive oxygen species [Truong, D., Eghbal, M., Hindmarsh, W., Roth, Sh., O'Brien, P., 2006. Molecular mechanisms of hydrogen sulfide toxicity. Drug Metab. Rev. 38, 733-744]. In the following, evidence is presented supporting the use of hydroxocobalamin (vitamin B(12a)) as an antidote against H(2)S poisoning. More than 60% of the mice administered 35 mg/kg (0.63 mmol/kg) of NaSH (LD(90)) survived (at 24 h) when hydroxocobalamin (0.25 mmol/kg) was given after NaSH administration whereas less than 15% of the mice survived without hydroxocobalamin. Hydroxocobalamin (50-100 microM) or cobalt (50-100 microM) also prevented hepatocyte cytotoxicity induced by NaSH (500 microM). Furthermore, adding hydroxocobalamin 60 min later than NaSH still showed some protective activity. Catalytic amounts of hydroxocobalamin or cobalt added to a solution containing NaSH caused the disappearance of NaSH and induced oxygen uptake, indicative of NaSH oxidation and Co reduction, respectively.

Topics: Animals; Antidotes; Catalase; Cell Survival; Cell-Free System; Cobalt; Dose-Response Relationship, Drug; Environmental Pollutants; Hepatocytes; Hydrogen Sulfide; Hydroxocobalamin; In Vitro Techniques; Lethal Dose 50; Male; Mice; Oxidation-Reduction; Oxygen; Poisoning; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Sulfides; Time Factors; Vitamin B Complex

Topics: Acute Disease; Animals; Antidotes; Clinical Trials as Topic; Cyanides; Drug Evaluation, Preclinical; Emergency Medical Services; Humans; Hydroxocobalamin; Poisoning

The efficacy of hydroxocobalamin for acute cyanide poisoning was compared with that of saline vehicle in dogs.. 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.. 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%).. Hydroxocobalamin reversed cyanide toxicity and reduced mortality in a canine model.

Topics: Acute Disease; Animals; Antidotes; Blood Pressure; Dogs; Dose-Response Relationship, Drug; Female; Heart Rate; Hemodynamics; Hydroxocobalamin; Lactic Acid; Male; Models, Animal; Neurologic Examination; Poisoning; Potassium Cyanide; Random Allocation; Respiratory Function Tests; Sodium Chloride

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.. 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.. 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.. Hydroxocobalamin has a risk:benefit ratio rendering it suitable for prehospital use in the management of acute cyanide poisoning caused by smoke inhalation.

Topics: Adult; Antidotes; Cyanides; Emergency Medical Services; Female; Fires; Glasgow Coma Scale; Heart Arrest; Hemodynamics; Humans; Hydroxocobalamin; Male; Middle Aged; Paris; Poisoning; Retrospective Studies; Smoke Inhalation Injury; Survival Analysis

Topics: Acute Disease; Antidotes; Humans; Hydroxocobalamin; Poisoning; Potassium Cyanide

Seven cases of hydrogen cyanide gas poisoning which occurred in an industrial building in Hong Kong are presented here. Two of them were more severely injured and required specific antidotal treatment. The other five were mild and responded to supportive treatment alone. All except one patient recovered completely. Cyanide poisoning is relatively uncommon in urbanized area, so high index of suspicion is important for early diagnosis and treatment. We believe that prevention of cyanide poisoning can be achieved by proper storage of chemicals, and by enforcing rescuers to wear special chemical protective clothing to avoid systemic poisoning because of dermal absorption of hydrogen cyanide gas. As there are newer and safer cyanide antidotes available, each emergency department should have a stock of updated products such as hydroxocobalamin.

Topics: Adult; Antidotes; Chemical Industry; Decontamination; Drug Storage; Emergency Medical Technicians; Emergency Treatment; Female; Humans; Hydrogen Cyanide; Hydroxocobalamin; Male; Middle Aged; Nitrates; Occupational Exposure; Oxygen Inhalation Therapy; Pentanols; Poisoning; Protective Clothing

Topics: Antidotes; Carbon Monoxide Poisoning; Cyanides; Drug Therapy, Combination; Humans; Hydroxocobalamin; Poisoning; Sodium Nitrite

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.. 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.. 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).. 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.

Topics: Analysis of Variance; Animals; Antidotes; Cobalt; Cyanides; Diaphragm; Dose-Response Relationship, Drug; Drug Evaluation, Preclinical; Heart; Hydroxocobalamin; Myocardium; Poisoning; Rats; Rats, Wistar

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.

Topics: Antidotes; Chromatography, High Pressure Liquid; Cyanides; Humans; Hydroxocobalamin; Luminescent Measurements; Poisoning; Scintillation Counting; Spectrophotometry, Ultraviolet; Vitamin B 12

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.

Topics: Animals; Critical Illness; Cyanides; Humans; Hydroxocobalamin; Hypertension; Nitroprusside; Poisoning

In all probability the future progress in the "molecular" approach of therapy in acute poisoning within the next 20 years or so will be more rapid than the "mechanistic" approach, which undoubtedly has brought considerable improvements in the overall survival of these patients in the past. Principally molecular antidotes can act on three different levels, a) prior to the cellular targets (e.g. through modifications of toxokinetics), b) at specific cellular receptors through competition for binding (e.g. naloxone and flumazenil), and c) after the receptor sites through unspecific counteraction of toxic effects (e.g. betablockers for intoxications with theophylline). Immune-antidotes act prior to cellular receptors. Examples are the digoxin antibodies and the anti-venoms as well as the very recently developed and not yet clinically tested antibodies against antidepressive drugs and against colchicine. Two newer antidotes, the 4-methylpyrazole and the hydroxocobalamin, act also prior the cellular targets of the corresponding toxic compounds. Thus, 4-Methylpyrazole decreases the degradation of ethylene-glycol by inhibiting alcohol dehydrogenase, which results in a higher excretion of unchanged ethylene-glycol in urine. Hydroxycobalamin complexes with cyanides to form the physiologic vitamin B12. In order to allow an equimolar neutralization of ingested cyanides a concentrated preparation containing 5 g of hydroxycobalamin was developed, the pharmacokinetic properties of which are discussed.

Topics: Antidotes; Binding, Competitive; Cyanides; Ethylene Glycols; Fomepizole; Humans; Hydroxocobalamin; Immunotherapy; Pharmaceutical Preparations; Poisoning; Pyrazoles

Hydroxocobalamin is a rapid and powerful antidote in acute cyanide poisoning. The effects of hydroxocobalamin (0.1, 0.3, and 1 mM) on intrinsic myocardial contractility were studied on isolated rat cardiac papillary muscles (n = 10). Whatever the concentration, hydroxocobalamin did not modify the active isometric force and a slight increase in maximum unloaded shortening velocity was noted at 1 mM. Only 0.3 mM significantly impaired contraction-relaxation coupling under low load, suggesting a slight decrease in sarcoplasmic reticulum function. No changes in contraction-relaxation coupling under heavy load were noted, suggesting the lack of modification of myofilament calcium sensitivity. These results suggest that hydroxocobalamin does not induce noticeable changes in intrinsic myocardial contractility. An indirect mechanism might be involved in the previously reported decrease in cardiac function at supratherapeutic concentrations of hydroxocobalamin.

Topics: Animals; Calcium Channels; Cyanides; Hemodynamics; Hydroxocobalamin; Myocardial Contraction; Papillary Muscles; Poisoning; Rats

Topics: Cyanides; Fires; Humans; Hydroxocobalamin; Poisoning; Smoke Inhalation Injury; Thiosulfates

Topics: Acidosis; Adult; Cyanides; Cyanosis; Gastric Lavage; Gastrointestinal Hemorrhage; Humans; Hydrogen Cyanide; Hydrogen-Ion Concentration; Hydroxocobalamin; Hypotension; Liver; Middle Aged; Poisoning; Suicide; Time Factors; Vitamin B 12

Topics: Acute Disease; Adult; Antidotes; Child, Preschool; Emergencies; Female; Humans; Hydrogen Cyanide; Hydroxocobalamin; Male; Middle Aged; Poisoning

Topics: Animals; Blood Circulation; Blood Pressure; Cats; Edetic Acid; Femoral Artery; Hydrogen Cyanide; Hydroxocobalamin; Phenols; Poisoning; Pulse; Respiration

Topics: Antidotes; Atropine; Chelating Agents; Cyanides; Deferoxamine; Dimercaprol; Edetic Acid; Humans; Hydroxocobalamin; Metals; Nitrites; Penicillamine; Pentetic Acid; Phenols; Phosphates; Poisoning; Pralidoxime Compounds; Thiosulfates

Topics: Animals; Antidotes; Cyanides; Guinea Pigs; Hydrogen Cyanide; Hydroxocobalamin; Lagomorpha; Mice; Poisoning; Rabbits; Research; Toxicology

Topics: Autonomic Nervous System Diseases; Barbiturates; Biomedical Research; Blood Chemical Analysis; Carbon Monoxide Poisoning; Cerebrovascular Disorders; Chemical Phenomena; Chemistry; Humans; Hydroxocobalamin; Mental Disorders; Neuralgia; Neuritis; Neurology; Pharmacology; Poisoning; Vitamin B 12

The antidotal potency of a cobalt salt (acetate), of dicobalt edetate, of hydroxocobalamin and of cobinamide against hydrocyanic acid was examined mainly on mice and rabbits. All the compounds were active antidotes for up to twice the LD50; under some conditions for larger doses. The most successful was cobalt acetate for rabbits (5xLD50), which was effective at a molar cyanide/cobalt (CN/Co) ratio of 5, but had as a side-effect intense purgation. Hydroxocobalamin was irregular in action, but on the whole was most effective for mice (4.5xLD50 at a molar ratio of 1), and had no apparent side effects. Dicobalt edetate, at molar ratios of up to 2, was more effective for rabbits (3xLD50) than for mice (2xLD50), but had fewer side effects than cobalt acetate. The effect of thiosulphate was to augment the efficacy of dicobalt edetate and, in mice, that of hydroxocobalamin; but, apparently, in rabbits, to reduce that of hydroxocobalamin. Cobinamide, at a molar ratio of 1, was slightly more effective than hydroxocobalamin on rabbits and also less irregular in its action. Cobalt acetate by mouth was effective against orally administered hydrocyanic acid. The oxygen uptake of the body, reduced by cyanide, is rapidly reinstated when one of the cobalt antidotes has been successfully administered.

Topics: Acetates; Animals; Antidotes; Cobalt; Cyanides; Edetic Acid; Hydrogen Cyanide; Hydroxocobalamin; Lagomorpha; Metabolism; Mice; Pharmacology; Poisoning; Rabbits; Research; Salts; Thiosulfates; Toxicology