Hydrogen cyanide and carboxyhemoglobin assessment in an open space fire-related fatality.

Hydrogen cyanide (HCN) can be a major contributory factor in death from fire-related inhalation injury. Although carbon monoxide (CO) is considered the lethal agent of smoke in fires, its liability as a cause of death is sometimes debatable. The purpose of this report is to present the case of an 80-year-old man with locomotor disabilities who died due to an open space fire of vegetation debris and household waste in his yard. We evaluated here the concentrations of HCN and carboxyhemoglobin (COHb) and their contribution to the mechanism of death. In addition, the risk factors and the contributing effect of the factors that compose the complex toxic environment that develops in fires were discussed. COHb was determined by spectrophotometry as recommended by Katsumata et al. in 1982. HCN was determined with ninhydrin in postmortem blood samples after removal with 20% phosphoric acid and capture in a potassium carbonate solution. A toxic concentration of 1.3 µg ml-1 HCN and a lethal COHb level of 73.7% were determined in the blood samples. Although death was mainly attributed to CO poisoning and extremely severe burns in this open space burning case, the additive effect of HCN in the mechanism of death was also highlighted. The results suggested the possibility that the man's clothing may have played an important role in the production of HCN in this open space fire, as well as other types of garbage that were burned.

An inhalational swine model for the characterization of physiological effects and toxicological profile associated with cyanide poisoning.

Cyanides are highly toxic compounds that have been used as weapons of terrorism throughout history. Cyanide (CN) is acutely toxic by all routes of administration; however, inhalation is the main exposure route. To adequately test effective countermeasures against inhalational CN threats, robust and well-characterized animal models are needed. This paper describes the initial development of a hydrogen cyanide (HCN) exposure swine model for documenting the physiological effects and toxicological profile during and after HCN inhalation exposure. Animals were implanted with telemetry transmitters for heart rate (HR), blood pressure, and electrocardiogram monitoring, and vascular access ports for serial blood collections. Nine female swine were exposed to HCN concentrations of 500 ± 6 ppm while breathing parameters were monitored real-time. Inhaled HCN doses ranged from 2.02 to 2.83 mg/kg. Clinical signs included vocalization, agitation, salivation, respiratory distress and apnea. After HCN exposure initiation, systemic arterial pressure fell dramatically with a concomitant increase in HR. Blood samples were collected to determine CN blood levels using LC-MS/MS and blood gas analysis. In summary, the developed HCN inhalation swine model permitted documentation of the physiological effects associated with CN poisoning. This model could be used to evaluate potential CN medical countermeasures in the event of a public health emergency stemming from inhalational CN threats.

Physiologically based pharmacokinetic modeling of hydrogen cyanide levels in human breath.

Hydrogen cyanide (HCN) is a potent and fast-acting toxin increasingly recognized as an important cause of death in fire victims. Prompt diagnosis and treatment of cyanide poisoning are essential to avoid fatalities. Unfortunately, there are at present few rapid diagnostic methods. A noninvasive methodology would be to use HCN in exhaled air as a marker for systemic exposure. To explore this possibility, we developed a preliminary physiologically based pharmacokinetic model. The model suggests that breath HCN levels following inhalation exposure at near-lethal and lethal conditions are 0.1-1 ppm, i.e., one to two orders of magnitude higher than the background breath level of about 0.01 ppm in unexposed subjects. Hence, our results imply that breath analysis may be used as a rapid diagnostic method for cyanide poisoning.

In vitro absorption of atmospheric carbon monoxide and hydrogen cyanide in undisturbed pooled blood.

Blood samples from aircraft accident victims are analyzed for carboxyhemoglobin (COHb) and cyanide ion (CN(-)). Such victims often suffer open wounds near the autopsy blood collection sites. Many aircraft crashes result in fires that fill the victim's atmosphere with smoke that is rich in carbon monoxide (CO) and hydrogen cyanide (HCN). It is important to determine whether pooled blood in those wounds may have absorbed these gases after death, which could lead one to erroneously conclude that the presence of COHb and CN(-) in blood was the result of breathing in these gases. A laboratory desiccator was used as a chamber to establish whether CO or HCN may be absorbed in undisturbed, pooled blood. COHb levels were 4.3-11.0% after exposure to CO (5,532, 8,298, 11,064, 22,129 and 33,193 ppm) for 30 and 60 min. Blood CN(-) concentrations (1.43-5.01 µg/mL) increased with exposure to HCN at 100 and 200 ppm, each at 15, 30, 45 and 60 min. The observed COHb increases do not exclude the possibility for higher COHb levels in blood exposed to highly CO-rich atmospheres, but there is a strong potential for CN(-) levels to increase by the absorption of atmospheric HCN. Thus, postmortem COHb and CN(-) levels should be carefully interpreted.

Prevalence of hydrogen cyanide and carboxyhaemoglobin in victims of smoke inhalation during enclosed-space fires: a combined toxicological risk.

BACKGROUND: Hydrogen cyanide (HCN) is one of the most toxic components of fire smoke, but insufficient attention is paid to its potential role as a cause of injury or death in victims (alive or dead) of enclosed-space fires. OBJECTIVE: To analyse the prevalence of toxic HCN exposure in fire victims and factors that may influence its toxicity, particularly the co-presence of carbon monoxide (CO) and ethanol. MATERIALS AND METHODS: Blood samples from fire victims and persons rescued from fires were analysed. RESULTS: A positive result for HCN (mean concentration 16.83 mg/l) was detected in blood samples from 169 of 285 fire-related deaths (59%). Ethanol was present in 91 (65%) of 139 samples with coincident presence of HCN and carboxyhaemoglobin (COHb). HCN (mean 4.0 mg/l) was also detected in 20 of 40 (50%) fire survivors. DISCUSSION: The high prevalence of coincident CO and HCN in enclosed-space, fire-related deaths should alert clinicians to suspect toxic HCN exposure in all persons rescued from fire with signs and symptoms of respiratory distress. CONCLUSIONS: Medical procedures in persons rescued from enclosed-space fires, especially in the pre-hospital setting, should be augmented to cover the possibility of toxic HCN exposure, particularly in individuals who do not respond to standard supportive therapy. Likewise, post-mortem investigations should routinely include assays for HCN when determining probable cause of death.

Toxicological findings in 889 fatally injured obese pilots involved in aviation accidents.

Prevalence of drugs in fatally injured obese pilots involved in aviation accidents has not been evaluated. Therefore, toxicological findings in such pilots (body mass index ≥30 kg/m(2) ) were examined in a data set derived from the Civil Aerospace Medical Institute's (CAMI's) Scientific Information System for 1990-2005. Aeromedical histories of these aviators were retrieved from the CAMI medical certification and toxicology databases, and the cause/factors in the related accidents from the National Transportation Safety Board's database. In 311 of the 889 pilots, carbon monoxide, cyanide, ethanol, and drugs were found, and glucose and hemoglobin A(1c) were elevated. Of the 889 pilots, 107 had an obesity-related medical history. The health and/or medical condition(s) of, and/or the use of ethanol and/or drugs by, pilots were the cause/factors in 55 (18%) of the 311 accidents. Drugs found were primarily for treating obesity-related medical conditions such as depression, hypertension, and coronary heart disease.

[Assessment of exposure to hydrogen cyanide in fire fatalities in the aspects of endogenous hydrogen cyanide production as a result of putrefaction processes in the deceased]. / Ocena ekspozycji na cyjanowodór u smiertelnych ofiar pozarów w aspekcie powstawania w zwlokach endogennego cyjanowodoru w procesach gnilno-rozkladowych.

On account of endogenous hydrogen cyanide (HCN) production in the deceased, it is not easy to assess exposure to HCN in people who died in fire involving closed rooms (flats, garages, cellars, etc). In the paper, the authors present the results of blood determinations of hydrogen cyanide in fatalities of explosions and fires occurring in coal-mines, as well as fires in closed rooms. It has been demonstrated that the time of exposure to a high temperature and the temperature itself hamper autolysis processes that lead to production of endogenous HCN in fire fatalities.

Hydrogen cyanide poisoning in a prison environment: a case report.

Cyanide poisoning is an important source of morbidity and mortality from smoke exposure in structural fires. This case involved administration of a cyanide antidote to a prisoner (male, 23 years) in France, discovered in cardiorespiratory arrest after about 30 minutes exposure to smoke from a burning mattress during an apparent suicide attempt. Smoke exposure, circulatory failure during initial resuscitation, and elevated blood cyanide and lactate led to the diagnosis of cyanide poisoning. Hydroxocobalamin (Cyanokit®), 5 g intravenous) was given immediately and on arrival at the hospital. Cardiopulmonary resuscitation restored cardiovascular function after 33 minutes. There were no neurological or other sequelae. Timely hydroxocobalamin administration contributed to full recovery from cardiorespiratory arrest secondary to cyanide poisoning from smoke inhalation. Hydroxocobalamin should be available to emergency medical teams attending fire scenes.

Carbon monoxide concentrations in the 2009 Victorian Bushfire disaster victims.

Blood was available for the estimation of carboxyhemoglobin saturation (COHb) in 30 of the 173 persons who died in the Victorian bushfires in February 2009. The ages of these 30 deaths ranged from 3 to 80 years and there were 8 females. 13 cases (43%) were considered negative (less than 5% COHb), 12 (40%) were between 5 and 40% COHb, 2 (6.7%) between 40 and 50% and 3 (10%) were greater than 50% COHb. There were 6 persons either found within a building or a car and the COHb in these cases ranged up to 69% (mean 50%). There were 5 cases where the location was unable to be determined as either indoor or outdoor due to the extensive nature of the fire. The remaining 19 deceased persons were all located outside in the open and the concentration of COHb in these cases ranged up to 30% (mean 19%). Hydrogen cyanide was only detected in two deceased persons at concentrations of 0.5 and 2.7 mg/L, respectively. 13 deceased were found to have soot in the airways following necropsy but this did not correlate with the COHb levels.

Effect of hyperbaric oxygen therapy on whole blood cyanide concentrations in carbon monoxide intoxicated patients from fire accidents.

BACKGROUND: Hydrogen cyanide (HCN) and carbon monoxide (CO) may be important components of smoke from fire accidents. Accordingly, patients admitted to hospital from fire accidents may have been exposed to both HCN and CO. Cyanide (CN) intoxication results in cytotoxic hypoxia leading to organ dysfunction and possibly death. While several reports support the use of hyperbaric oxygen therapy (HBO) for the treatment of severe CO poisoning, limited data exist on the effect of HBO during CN poisoning. HBO increases the elimination rate of CO haemoglobin in proportion to the increased oxygen partial pressure and animal experiments have shown that in rats exposed to CN intoxication, HBO can increase the concentration of CN in whole blood. OBJECTIVE: The purpose of the present study was to determine whole blood CN concentrations in fire victims before and after HBO treatment. MATERIALS AND METHODS: The patients included were those admitted to the hospital because of CO intoxication, either as fire victims with smoke inhalation injuries or from other exposures to CO. In thirty-seven of these patients we measured CN concentrations in blood samples, using a Conway/microdiffusion technique, before and after HBO. The blood samples consisted of the remaining 2 mL from the arterial blood gas analysis. CN concentration in blood from fire victims was compared to 12 patients from non-fire accidents but otherwise also exposed to CO intoxication. RESULTS: The mean WB-CN concentration before patients received HBO did not differ significantly between the two groups of patients (p = 0.42). The difference between WB-CN before and after HBO did not differ significantly between the two groups of patients (p = 0.7). Lactate in plasma before and after did not differ significantly between the two groups of patients. Twelve of the 25 fire patients and one of the non-fire patients had been given a dose of hydroxycobalamin before HBO. DISCUSSION AND CONCLUSION: CN concentrations in blood from patients admitted to hospital with CO intoxication and smoke inhalation exposure did not differ significantly from controls. Accordingly, we were not able to detect any changes in CN concentrations in blood after treatment with HBO. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00280579.

Toxic effects of prolonged administration of leaves of cassava (Manihot esculenta Crantz) to goats.

Cassava (Manihot esculenta Crantz) is a major source of dietary energy for humans and domestic animals in many tropical countries. However, consumption of cassava is limited by its characteristic content of cyanogenic glycosides. The present work aimed to evaluate the toxic effects of ingestion of cassava leaves by goats for 30 consecutive days, and to compare the results with the toxic effects of cyanide in goats, which have been described previously. Eight Alpine cross-bred female goats were divided into two equal groups, and were treated with ground frozen cassava leaves at a target dose of 6.0mg hydrogen cyanide (HCN)/kg/day (treated animals), or with ground hay and water only (control group) by gavage for 30 consecutive days. Blood samples were collected on days 0, 7, 15, 21, and 30 for biochemical panel and cyanide determination. At the end of the experiment, fragments of pancreas, thyroid gland, liver, kidney, lungs, heart, spleen, and the whole central nervous system were collected for histopathological examination. Clinical signs were observed in all goats treated with cassava on the first day of the experiment. From the second day the dose of cassava leaves was reduced to 4.5mgHCN/kg/day. No changes were found in the blood chemical panel. A mild increase in the number of resorption vacuoles in the thyroid follicular colloid, slight vacuolation of periportal hepatocytes, and spongiosis of the mesencephalon were found in goats treated with cassava. The pattern of lesions seen in the present goats was similar to what has been described previously in cyanide-dosed goats. Thus, the toxic effects of the ingestion of cassava leaves by goats can be attributed to the action of cyanide released from cyanogenic glycosides, and none of the effects was promoted by these glycosides directly.

Report of the investigation committee into the cyanide poisonings of Providence firefighters.

In the afternoon of March 23, 2006 a Providence firefighter was diagnosed as having cyanide poisoning after working at a building fire. In the aftermath of three fires at commercial and residential sites that day, eight additional firefighters (out of 28 tested) were found to have elevated levels of cyanide. Numerous other members reported symptoms consistent with cyanide poisoning, including headaches, weakness and fatigue, nausea, and shortness of breath. The Providence Fire Department (PFD) established a joint union management committee to review the situation.

[The effect of high temperature on the levels of selected endogenous compounds]. / Wplyw wysokiej temperatury na poziom wybranych zwiazków endogennych.

The authors present their research on the levels of carboxyhemoglobin, hydrogen cyanide and ethyl alcohol in the blood of 23 fatalities found in the extreme conditions (methane explosion, fire, high temperature) associated with a mining disaster. Determinations of the presence of carboxyhemoglobin, hydrogen cyanide, and ethyl alcohol were performed as soon as the blood samples were collected from the deceased. The concentration of ethyl alcohol ranged from 0.2 per thousand to 1.3 per thousand in 18 cases. Blood HbCO levels tested within the range of 11% to 83% in 17 cases. In six cases, HbCO tested negative, and the injuries found at autopsy indicated these individuals to have been killed at the moment of the explosion. Blood cyanide content tested negative in all the examined cases. The extreme conditions of the mining disaster, especially high temperature, to which the bodies were exposed, did not have any effect either on endogenous cyanide or carboxyhemoglobin, causing, however, a significant increase in the level of ethyl alcohol in the blood.

[Opinionating on the cause of poisoning and death in fire victims]. / Opiniowanie o przyczynie zatrucia i smierci w przypadku badania zwlok wydobytych z pozaru.

In the years 1995-2005, 273 cases of fatalities resulting from a fire were investigated in the Chair of Forensic Medicine, Medical University of Silesia, Katowice. To explain the circumstances and determine the cause of death, in each case, autopsies, as well as toxicological determinations of toxic gases, such as carbon monoxide or hydrogen cyanide, were carried out. Alcohol intoxication status of the victims was also determined. Based on the obtained results, comprehensive toxicological and medico-legal opinions on the cause of death of all the examined fire-associated fatalities were done.

Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation.

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 micromol/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.

[The role of ethanol in complex poisonings with carbon monoxide and hydrogen cyanide in fire victims]. / Rola etanolu w kompleksowych zatruciach tlenkiem wegla i cyjanowodorem u ofiar pozarów.

A total of 230 cases of deaths in burning spaces dating from the years 1995-2003 were investigated in Forensic Medicine Department, Silesian University of Medicine, Katowice. HbCO and HCN found in 177 blood samples ranged from 4-95 % (mean, 31,5 %) and 0,5-40,3 microg/ml (mean, 9,98 microg/ml), respectively. Moreover, ethanol was found in 122 blood samples. Its concentration ranged from 0,89-5,0 per thousand (mean, 1,45 per thousand). A comparative analysis of HbCO and HCN levels in the groups with and without ethanol showed that the range and the mean concentration of both these xenobiotics were higher in the group with no alcohol. It was also shown that the increased ethanol caused a drop in HbCO and HCN levels. To evaluate HbCO and HCN levels, the regression and correlation analysis was used.

Determination of cyanide in blood by isotope-dilution gas chromatography-mass spectrometry.

BACKGROUND: Cyanide (CN) is a lethal toxin. Quantification in blood is necessary to indicate exposure from many sources, including food, combustion byproducts, and terrorist activity. We describe an automated procedure based on isotope-dilution gas chromatography-mass spectrometry (ID GC/MS) for the accurate and rapid determination of CN in whole blood. METHODS: A known amount of isotopically labeled potassium cyanide (K13C15N) was added to 0.5 g of whole blood in a headspace vial. Hydrogen cyanide was generated through the addition of phosphoric acid, and after a 5-min incubation, 0.5 mL of the headspace was injected into the GC/MS at an oven temperature of -15 degrees C. The peak areas from the sample, 1H12C14N+, at m/z 27, and the internal standard, 1H13C15N+, at m/z 29, were measured, and the CN concentration was quantified by ID. The analysis time was 15 min for a single injection. RESULTS: We demonstrated method accuracy by measuring the CN content of unfrozen whole blood samples fortified with a known amount of CN. Intermediate precision was demonstrated by periodic analyses over a 14-month span. Relative expanded uncertainties based on a 95% level of confidence with a coverage factor of 2 at CN concentrations of 0.06, 0.6, and 1.5 microg/g were 8.3%, 5.4%, and 5.3%, respectively. The mean deviation from the known value for all concentrations was <4%. CONCLUSION: The automated ID GC/MS method can accurately and rapidly quantify nanogram per gram to microgram per gram concentrations of CN in blood.

Carboxyhemoglobin and blood cyanide concentrations in relation to aviation accidents.

INTRODUCTION: It is important in aviation accident investigations to determine if a fire occurred during flight or after the crash and to establish the source(s) of the toxic gases. METHODS: Bio-specimens from aviation accident fatalities are submitted to CAMI for analyses. In blood, CO is analyzed as carboxyhemoglobin (COHb) and hydrogen cyanide as cyanide (CN-). Analytical data were stored in a database, and this database was searched for the period of 1990-2002 for the presence of COHb and CN in the submitted cases. RESULTS: Out of 5945 cases, there were 223 (4%) cases wherein COHb was > or = 10%. Of the 223 cases, fire was reported with 201, no fire with 21, and undetermined fire status with 1. CN concentrations were at or above 0.25 microg x ml(-1) in 103 of the 201 fire-related cases. None of the 21 non-fire cases had CN-, but nicotine was detected in 9 of the cases. All non-fire cases with COHb > 30% (four cases) were associated with exhaust leaks. Of the 223 cases, COHb-CN- fractional toxic concentration (FTC) was lethal only in 31 cases with elevated CN levels. CONCLUSIONS: The presence of COHb and CN in elevated concentrations in the blood of victims found by autopsy to have died on impact would indicate an in-flight fire. In the absence of fire and CN-, the elevated COHb concentrations would suggest an exhaust leak, particularly at COHb > 30%. The findings of this study also suggest that, in addition to COHb, CN plays a detrimental role in fire-associated aviation accident fatalities.

[Levels of carbon monoxide and hydrogen cyanide in blood of fire victims in the autopsy material of the Department of Forensic Medicine, Medical University of Bialystok]. / Stezenia tlenku wegla i cyjanowodoru we krwi osób zmarlych w pozarach w materiale ZMS AM w Bialymstoku.

The authors present the results of toxicological examination of blood of fatal victims of fires in "closed" spaces. Hydrogen cyanide was present in 26 out of 64 postmortem blood samples. COHb was found in 52 cases. The hydrogen cyanide levels ranged from 0.8 to 39.2 microg/l, the COHb levels ranged from 16.0 to 85.0%. The level of hydrogen cyanide was determined by the pyrazolopyridine method modified by Nedoma, and the COHb level was determined by the Wolff method.

Effect of combined exposure to carbon monoxide and cyanides in selected forensic cases.

Carbon monoxide is a toxic gas with potentially lethal action, which forms as a result of incomplete combustion in conditions where there is a lack of oxygen and which, therefore, is present in varying percentages in environments where fire develops. In addition to carbon monoxide, other factors such as cyanide may contribute or might actually be the primary cause of a subject's demise. In cases of exposure to both substances, the role of cyanide as a toxic/lethal agent in death by asphyxiation is still not clear: some authors attribute a primary action to such a gas in causing the demise, others consider carbon monoxide to be the only cause of the lethal event. For this reason it is in the interest of forensic medicine to study all lethal cases of exposure to toxic substances originating from fires of various types of materials, in order to determine information regarding kinetic action and the possible strengthening of the effect of the two substances. Two case studies are presented here, in which the results of the toxicological examinations are quite different, and the contributions of CO and HCN in a fire asphyxiation are considered.