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Alan H. Hall - One of the best experts on this subject based on the ideXlab platform.
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Sodium thiosulfate or hydroxocobalamin for the empiric treatment of Cyanide Poisoning
Annals of emergency medicine, 2006Co-Authors: Alan H. Hall, Richard C. Dart, Gregory M. BogdanAbstract:Cyanide Poisoning must be seriously considered in victims of smoke inhalation from enclosed space fires; it is also a credible terrorism threat agent. The treatment of Cyanide Poisoning is empiric because laboratory confirmation can take hours or days. Empiric treatment requires a safe and effective antidote that can be rapidly administered by either out-of-hospital or emergency department personnel. Among several Cyanide antidotes available, sodium thiosulfate and hydroxocobalamin have been proposed for use in these circumstances. The evidence available to assess either sodium thiosulfate or hydroxocobalamin is incomplete. According to recent safety and efficacy studies in animals and human safety and uncontrolled efficacy studies, hydroxocobalamin seems to be an appropriate antidote for empiric treatment of smoke inhalation and other suspected Cyanide Poisoning victims in the out-of-hospital setting. Sodium thiosulfate can also be administered in the out-of-hospital setting. The efficacy of sodium thiosulfate is based on individual case studies, and there are contradictory conclusions about efficacy in animal models. The onset of antidotal action of sodium thiosulfate may be too slow for it to be the only Cyanide antidote for emergency use. Hydroxocobalamin is being developed for potential introduction in the United States and may represent a new option for emergency personnel in cases of suspected or confirmed Cyanide Poisoning in the out-of-hospital setting.
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Pediatric Cyanide Poisoning: causes, manifestations, management, and unmet needs.
Pediatrics, 2006Co-Authors: Robert J. Geller, Claudia L. Barthold, Jane A. Saiers, Alan H. HallAbstract:Confirmed cases of childhood exposure to Cyanide are rare despite multiple potential sources including inhalation of fire smoke, ingestion of toxic household and workplace substances, and ingestion of cyanogenic foods. Because of its infrequent occurrence, medical professionals may have difficulty recognizing Cyanide Poisoning, confirming its presence, and treating it in pediatric patients. The sources and manifestations of acute Cyanide Poisoning seem to be qualitatively similar between children and adults, but children may be more vulnerable than adults to Poisoning from some sources. The only currently available antidote in the United States (the Cyanide antidote kit) has been used successfully in children but has particular risks associated with its use in pediatric patients. Because hemoglobin kinetics vary with age, methemoglobinemia associated with nitrite-based antidotes may be excessive at standard adult dosing in children. A Cyanide antidote with a better risk/benefit ratio than the current agent available in the United States is desirable. The vitamin B12 precursor hydroxocobalamin, which has been used in Europe, may prove to be an attractive alternative to the Cyanide antidote kit for pediatric patients. In this article we review the available data on the sources, manifestations, and treatment of acute Cyanide Poisoning in children and discuss unmet needs in the management of pediatric Cyanide Poisoning.
Frédéric J. Baud - One of the best experts on this subject based on the ideXlab platform.
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Antidotes for acute Cyanide Poisoning.
Current pharmaceutical biotechnology, 2012Co-Authors: Stephen W. Borron, Frédéric J. BaudAbstract:Cyanide Poisoning can present in multiple ways, given its widespread industrial use, presence in combustion products, multiple physical forms, and chemical structures. The primary target of toxicity is mitochondrial cytochrome oxidase. The onset and severity of Poisoning depend on the route, dose, physicochemical structure and other variables. Common Poisoning features include dyspnea, altered respiratory patterns, abnormal vital signs, altered mental status, seizures, and lactic acidosis. Our present knowledge supports Cyanide Poisoning treatment based on excellent supportive care with adjunctive antidotal therapy. Multiple antidotes exist and vary in regional availability. All currently marketed antidotes appear to be effective. Antidotal mechanisms include chelation, formation of stable, less toxic complexes, methemoglobin induction, and sulfane sulfur supplementation for detoxification by endogenous rhodanese. Each antidote has advantages and disadvantages. For example, hydroxocobalamin is safer than the methemoglobin inducers in patients with smoke inhalation. Research for new, safer and more effective Cyanide antidotes continues.
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prospective study of hydroxocobalamin for acute Cyanide Poisoning in smoke inhalation
Annals of Emergency Medicine, 2007Co-Authors: Stephen W. Borron, Frédéric J. Baud, P Barriot, M Imbert, C BismuthAbstract:Study objective To assess outcomes in patients treated with hydroxocobalamin at the fire scene or in the ICU for suspected smoke inhalation-associated Cyanide Poisoning. Methods Adult smoke inhalation victims with suspected Cyanide Poisoning as determined by soot in the face, mouth, or nose or expectorations and neurologic impairment received an intravenous infusion of hydroxocobalamin 5 g (maximum 15 g) at the fire scene or in the ICU in this observational case series conducted from 1987 to 1994. Blood Cyanide specimens were collected before administration of hydroxocobalamin. The threshold for Cyanide toxicity was predefined as greater than or equal to 39 μmol/L. Results The sample included 69 patients (mean age 49.6 years; 33 men), of whom 39 were comatose. Out-of-hospital deaths were excluded. Fifty of the 69 patients (72%) admitted to the ICU survived after administration of hydroxocobalamin. In the group in which Cyanide Poisoning was confirmed a posteriori (n=42), 67% (28/42) survived after administration of hydroxocobalamin. The most common adverse events were chromaturia (n=6), pink or red skin discoloration (n=4), hypertension (n=3), erythema (n=2), and increased blood pressure (n=2). No serious adverse events were attributed to hydroxocobalamin. Laboratory tests revealed transient alterations in renal and hepatic function consistent with the critical condition of the patients and mild anemia consistent with progressive hemodilution. Conclusion Empiric administration of hydroxocobalamin was associated with survival among 67% of patients confirmed a posteriori to have had Cyanide Poisoning. Hydroxocobalamin was well tolerated irrespective of the presence of Cyanide Poisoning. Hydroxocobalamin appears to be safe for the out-of-hospital treatment of presumptive Cyanide Poisoning from smoke inhalation.
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Hydroxocobalamin for severe acute Cyanide Poisoning by ingestion or inhalation.
The American journal of emergency medicine, 2007Co-Authors: Stephen W. Borron, Bruno Mégarbane, Frédéric J. Baud, Chantal BismuthAbstract:This chart review was undertaken to assess efficacy and safety of hydroxocobalamin for acute Cyanide Poisoning. Hospital records of the Fernand Widal and Lariboisiere Hospitals were reviewed for intensive care unit admissions with Cyanide Poisoning for which hydroxocobalamin was used as first-line treatment from 1988 to 2003. Smoke inhalation cases were excluded. Hydroxocobalamin (5-20 g) was administered to 14 consecutive patients beginning a median 2.1 hours after Cyanide ingestion or inhalation. Ten patients (71%) survived and were discharged. Of the 11 patients with blood Cyanide exceeding the typically lethal threshold of 100 lmol/L, 7 survived. The most common hydroxocobalamin-attributed adverse events were chromaturia and pink skin discoloration. Severe Cyanide Poisoning of the nature observed in most patients in this study is frequently fatal. That 71% of patients survived after treatment with hydroxocobalamin suggests that hydroxocobalamin as first-line antidotal therapy is effective and safe in acute Cyanide Poisoning.
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Antidotal treatment of Cyanide Poisoning.
Journal of the Chinese Medical Association : JCMA, 2003Co-Authors: Bruno Mégarbane, Arnaud Delahaye, Dany Goldgran-toledano, Frédéric J. BaudAbstract:Cyanide Poisoning may result from different exposures: residential fires, industrial accidents, drug and plant intoxication. Clinical features include coma, respiratory arrest and cardiovascular collapse. The biological hallmark is lactic acidosis. A plasma lactate concentration > or = 10 mmol/L in fire victims without severe burns and > or = 8 mmol/L in pure Cyanide poisoned patients is a sensitive and specific indicator of Cyanide intoxication. Many antidotes are available and efficient. However, therapeutic strategies are still debated. Our objective was to compare conventional treatments to hydroxocobalamin. This article reviews the literature on Cyanide Poisoning treatment. Conventional treatment of Cyanide Poisoning includes decontamination, supportive and specific treatment. Decontamination should be adapted to the route of Poisoning and never postpone supportive treatment. Basic life support includes immediate administration of high flow of oxygen, airway protection and cardiopulmonary resuscitation. Advanced life support includes mechanical ventilation, catecholamine and sodium bicarbonate infusion. Supportive treatment is efficient but does not modify the time course or the body burden of Cyanide. Numerous antidotes are available. Oxygen counteracts efficiently Cyanide action at the mitochondrial level. Sodium thiosulfate, methemoglobin forming agents and cobalt compounds act efficiently by complexing or transforming Cyanide into non-toxic stable derivatives. However, regarding the main clinical condition of Cyanide Poisoning, i.e. smoke inhalation, we should take into account not only the efficiency of antidotes but also their safety. Sodium thiosulfate is both efficient and safe, but acts with delay. Methemoglobin-forming agents are potent, but due to the transformation of hemoglobin into methemoglobin, they impair tissue delivery of oxygen. Experimental data showed increased mortality in carbon monoxide- and Cyanide-poisoned rats treated with these agents. Cobalt EDTA and hydroxocobalamin are efficient and act immediately. Cobalt EDTA is more potent on a molar basis; however, numerous side effects limit its use to evidenced Cyanide Poisoning. In a prospective study, hydroxocobalamin appeared safe in fire victims with or without Cyanide Poisoning. The only reported side effect was a red coloration of skin and urine. In conclusion, antidotes are beneficial in Cyanide Poisoning. In suspected Cyanide-poisoned patients, we recommend the use of hydroxocobalamin as first-line antidote, owing to its safety. In massive Cyanide Poisoning, due to the limited potency of hydroxocobalamin, continuous infusion of sodium thiosulfate should be associated.
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Relation between plasma lactate and blood Cyanide concentrations in acute Cyanide Poisoning
BMJ, 1996Co-Authors: Frédéric J. Baud, Stephen W. Borron, Eric Bavoux, A. Astier, Jerome R. HoffmanAbstract:Cyanide Poisoning produces rapid blockade of cellular respiration due to binding to cytochromeaa3, resulting in accumulation of lactate. Lactic acidosis is a recognised hallmark of acute Cyanide Poisoning in humans.1 2 The time course of lactic acidosis, however, has not been well described in relation to evolving blood Cyanide concentrations. We studied the relation of blood Cyanide to plasma lactate concentrations in a patient with pure acute Cyanide Poisoning. A 63 year old man called for help immediately after suicidal ingestion of a single potassium Cyanide capsule. He was conscious on arrival of ambulance staff, but apnoea rapidly supervened, followed by cardiac arrest. Cardiopulmonary resuscitation, endotracheal intubation with 100% pure …
Adriano Chan - One of the best experts on this subject based on the ideXlab platform.
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Cisplatin Analogs Confer Protection against Cyanide Poisoning
Cell chemical biology, 2017Co-Authors: Anjali K. Nath, Adriano Chan, Sari B. Mahon, Xu Shi, Devin L. Harrison, Jordan Morningstar, Patrick Sips, Jangwoen Lee, Calum A. Macrae, Gerry R. BossAbstract:Cisplatin holds an illustrious position in the history of chemistry most notably for its role in the virtual cure of testicular cancer. Here we describe a role for this small molecule in Cyanide detoxification in vivo. Cyanide kills organisms as diverse as insects, fish, and humans within seconds to hours. Current antidotes exhibit limited efficacy and are not amenable to mass distribution requiring the development of new classes of antidotes. The binding affinity of the Cyanide anion for the positively charged metal platinum is known to create an extremely stable complex in vitro. We therefore screened a panel of diverse cisplatin analogs and identified compounds that conferred protection from Cyanide Poisoning in zebrafish, mice, and rabbits. Cumulatively, this discovery pipeline begins to establish the characteristics of platinum ligands that influence their solubility, toxicity, and efficacy, and provides proof of concept that platinum-based complexes are effective antidotes for Cyanide Poisoning.
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The combination of cobinamide and sulfanegen is highly effective in mouse models of Cyanide Poisoning.
Clinical Toxicology, 2011Co-Authors: Adriano Chan, Alexandre R. Monteil, Steven E. Patterson, Herbert T. Nagasawa, Jackie E. Briggs, Joseph A. Kozocas, Sari B. Mahon, Matthew Brenner, Daune L. Crankshaw, Renate B. PilzAbstract:Context. Cyanide is a component of smoke in residential and industrial fires, and accidental exposure to Cyanide occurs in a variety of industries. Moreover, Cyanide has the potential to be used by terrorists, particularly in a closed space such as an airport or train station. Current therapies for Cyanide Poisoning must be given by intravenous administration, limiting their use in treating mass casualties. Objective. We are developing two new Cyanide antidotes – cobinamide, a vitamin B12 analog, and sulfanegen, a 3-mercaptopyruvate prodrug. Both drugs can be given by intramuscular administration, and therefore could be used to treat a large number of people quickly. We now asked if the two drugs would have an augmented effect when combined. Materials and methods. We used a non-lethal and two different lethal models of Cyanide Poisoning in mice. The non-lethal model assesses neurologic recovery by quantitatively evaluating the innate righting reflex time of a mouse. The two lethal models are a Cyanide inj...
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Cobinamide is superior to other treatments in a mouse model of Cyanide Poisoning.
Clinical toxicology (Philadelphia Pa.), 2010Co-Authors: Adriano Chan, Gerry R. Boss, Maheswari Balasubramanian, William Blackledge, Othman Mohammad, Luis Alvarez, Timothy D. BigbyAbstract:Context. Cyanide is a rapidly acting cellular poison, primarily targeting cytochrome c oxidase, and is a common occupational and residential toxin, mostly via smoke inhalation. Cyanide is also a potential weapon of mass destruction, with recent credible threats of attacks focusing the need for better treatments, as current Cyanide antidotes are limited and impractical for rapid deployment in mass casualty settings. Objective. We have used mouse models of Cyanide Poisoning to compare the efficacy of cobinamide (Cbi), the precursor to cobalamin (vitamin B12), to currently approved Cyanide antidotes. Cbi has extremely high affinity for Cyanide and substantial solubility in water. Materials and Methods. We studied Cbi in both an inhaled and intraperitoneal model of Cyanide Poisoning in mice. Results. We found Cbi more effective than hydroxocobalamin, sodium thiosulfate, soldium nitrite, and the combination of sodium thiosulfate–sodium nitrite in treating Cyanide Poisoning. Compared to hydroxocobalamin, Cbi wa...
Stephen W. Borron - One of the best experts on this subject based on the ideXlab platform.
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Management of Cyanide Poisoning
Oxford Medicine Online, 2016Co-Authors: Stephen W. BorronAbstract:Acute Cyanide Poisoning poses vital diagnostic and therapeutic challenges for emergency physicians and intensivists. While it presents certain unique clinical features, Cyanide Poisoning may be confused with other entities. Definitive, contemporaneous diagnosis at the bedside is impossible in most hospitals. A thorough anamnesis, rapid physical assessment, and evaluation of key laboratory indicators often point the clinician in the right direction. Smoke inhalation from structure fires represents the most frequent source of Cyanide Poisoning. Symptom onset may be gradual in the case of skin exposures to Cyanide or ingestion of compounds that are metabolized to Cyanide. However, acute Cyanide Poisoning presents as a syndrome of rapidly evolving and deteriorating vital signs, profound neurological and cardiovascular dysfunction, and if therapeutic interventions are not timely and adapted, death. There is little time for diagnostic testing: one must act! The sine qua non of treatment is excellent supportive care, with aggressive airway management, support of blood pressure, and correction of acidosis. Treatment of acidosis is particularly relevant in the case of Cyanide. Rapid administration of specific Cyanide antidotes may be lifesaving. While geographic variations exist in antidote availability, most commercially available antidotes have been demonstrated to be effective. Hydroxocobalamin and sodium thiosulphate, both safe in the setting of smoke inhalation, offer the highest therapeutic index, a critical consideration when the diagnosis is uncertain.
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Antidotes for acute Cyanide Poisoning.
Current pharmaceutical biotechnology, 2012Co-Authors: Stephen W. Borron, Frédéric J. BaudAbstract:Cyanide Poisoning can present in multiple ways, given its widespread industrial use, presence in combustion products, multiple physical forms, and chemical structures. The primary target of toxicity is mitochondrial cytochrome oxidase. The onset and severity of Poisoning depend on the route, dose, physicochemical structure and other variables. Common Poisoning features include dyspnea, altered respiratory patterns, abnormal vital signs, altered mental status, seizures, and lactic acidosis. Our present knowledge supports Cyanide Poisoning treatment based on excellent supportive care with adjunctive antidotal therapy. Multiple antidotes exist and vary in regional availability. All currently marketed antidotes appear to be effective. Antidotal mechanisms include chelation, formation of stable, less toxic complexes, methemoglobin induction, and sulfane sulfur supplementation for detoxification by endogenous rhodanese. Each antidote has advantages and disadvantages. For example, hydroxocobalamin is safer than the methemoglobin inducers in patients with smoke inhalation. Research for new, safer and more effective Cyanide antidotes continues.
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prospective study of hydroxocobalamin for acute Cyanide Poisoning in smoke inhalation
Annals of Emergency Medicine, 2007Co-Authors: Stephen W. Borron, Frédéric J. Baud, P Barriot, M Imbert, C BismuthAbstract:Study objective To assess outcomes in patients treated with hydroxocobalamin at the fire scene or in the ICU for suspected smoke inhalation-associated Cyanide Poisoning. Methods Adult smoke inhalation victims with suspected Cyanide Poisoning as determined by soot in the face, mouth, or nose or expectorations and neurologic impairment received an intravenous infusion of hydroxocobalamin 5 g (maximum 15 g) at the fire scene or in the ICU in this observational case series conducted from 1987 to 1994. Blood Cyanide specimens were collected before administration of hydroxocobalamin. The threshold for Cyanide toxicity was predefined as greater than or equal to 39 μmol/L. Results The sample included 69 patients (mean age 49.6 years; 33 men), of whom 39 were comatose. Out-of-hospital deaths were excluded. Fifty of the 69 patients (72%) admitted to the ICU survived after administration of hydroxocobalamin. In the group in which Cyanide Poisoning was confirmed a posteriori (n=42), 67% (28/42) survived after administration of hydroxocobalamin. The most common adverse events were chromaturia (n=6), pink or red skin discoloration (n=4), hypertension (n=3), erythema (n=2), and increased blood pressure (n=2). No serious adverse events were attributed to hydroxocobalamin. Laboratory tests revealed transient alterations in renal and hepatic function consistent with the critical condition of the patients and mild anemia consistent with progressive hemodilution. Conclusion Empiric administration of hydroxocobalamin was associated with survival among 67% of patients confirmed a posteriori to have had Cyanide Poisoning. Hydroxocobalamin was well tolerated irrespective of the presence of Cyanide Poisoning. Hydroxocobalamin appears to be safe for the out-of-hospital treatment of presumptive Cyanide Poisoning from smoke inhalation.
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Hydroxocobalamin for severe acute Cyanide Poisoning by ingestion or inhalation.
The American journal of emergency medicine, 2007Co-Authors: Stephen W. Borron, Bruno Mégarbane, Frédéric J. Baud, Chantal BismuthAbstract:This chart review was undertaken to assess efficacy and safety of hydroxocobalamin for acute Cyanide Poisoning. Hospital records of the Fernand Widal and Lariboisiere Hospitals were reviewed for intensive care unit admissions with Cyanide Poisoning for which hydroxocobalamin was used as first-line treatment from 1988 to 2003. Smoke inhalation cases were excluded. Hydroxocobalamin (5-20 g) was administered to 14 consecutive patients beginning a median 2.1 hours after Cyanide ingestion or inhalation. Ten patients (71%) survived and were discharged. Of the 11 patients with blood Cyanide exceeding the typically lethal threshold of 100 lmol/L, 7 survived. The most common hydroxocobalamin-attributed adverse events were chromaturia and pink skin discoloration. Severe Cyanide Poisoning of the nature observed in most patients in this study is frequently fatal. That 71% of patients survived after treatment with hydroxocobalamin suggests that hydroxocobalamin as first-line antidotal therapy is effective and safe in acute Cyanide Poisoning.
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Relation between plasma lactate and blood Cyanide concentrations in acute Cyanide Poisoning
BMJ, 1996Co-Authors: Frédéric J. Baud, Stephen W. Borron, Eric Bavoux, A. Astier, Jerome R. HoffmanAbstract:Cyanide Poisoning produces rapid blockade of cellular respiration due to binding to cytochromeaa3, resulting in accumulation of lactate. Lactic acidosis is a recognised hallmark of acute Cyanide Poisoning in humans.1 2 The time course of lactic acidosis, however, has not been well described in relation to evolving blood Cyanide concentrations. We studied the relation of blood Cyanide to plasma lactate concentrations in a patient with pure acute Cyanide Poisoning. A 63 year old man called for help immediately after suicidal ingestion of a single potassium Cyanide capsule. He was conscious on arrival of ambulance staff, but apnoea rapidly supervened, followed by cardiac arrest. Cardiopulmonary resuscitation, endotracheal intubation with 100% pure …
Robert J. Geller - One of the best experts on this subject based on the ideXlab platform.
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Pediatric Cyanide Poisoning: causes, manifestations, management, and unmet needs.
Pediatrics, 2006Co-Authors: Robert J. Geller, Claudia L. Barthold, Jane A. Saiers, Alan H. HallAbstract:Confirmed cases of childhood exposure to Cyanide are rare despite multiple potential sources including inhalation of fire smoke, ingestion of toxic household and workplace substances, and ingestion of cyanogenic foods. Because of its infrequent occurrence, medical professionals may have difficulty recognizing Cyanide Poisoning, confirming its presence, and treating it in pediatric patients. The sources and manifestations of acute Cyanide Poisoning seem to be qualitatively similar between children and adults, but children may be more vulnerable than adults to Poisoning from some sources. The only currently available antidote in the United States (the Cyanide antidote kit) has been used successfully in children but has particular risks associated with its use in pediatric patients. Because hemoglobin kinetics vary with age, methemoglobinemia associated with nitrite-based antidotes may be excessive at standard adult dosing in children. A Cyanide antidote with a better risk/benefit ratio than the current agent available in the United States is desirable. The vitamin B12 precursor hydroxocobalamin, which has been used in Europe, may prove to be an attractive alternative to the Cyanide antidote kit for pediatric patients. In this article we review the available data on the sources, manifestations, and treatment of acute Cyanide Poisoning in children and discuss unmet needs in the management of pediatric Cyanide Poisoning.
