Blood Cyanide Concentrations Research Articles

Diagnosis of lethal cyanide poisoning. Analysis by Anion-Exchange Chromatography with Pulsed AmperometricDetection.

Cyanide is a poison widely used in cases of suicide or homicide. Although various methods to identify and quantify this substance are reported in the literature, they are mainly validated on biological fluids (e.g., blood and urine). In the present study, the Anion‐Exchange Liquid Chromatography with Pulsed Amperometric Detection (IC‐PAD) method was validated on blood and, for the first time, on gastric content, and organs (brain, lung, and liver). For each matrix, linearity, accuracy, precision, limit of detection (LOD), lower limit of quantification (LLOQ), matrix interferences, and carryover were assessed. The samples were extracted by steam distillation in acid environment for the following analysis by IC‐PAD. Furthermore, cyanide values found in two real poisoning cases are reported. For each investigated matrix, the analytical method satisfied all acceptance criteria for validation: it showed a good precision and accuracy, selectivity, and sensitivity with no carryover and matrix interference. The extraction by steam distillation in acid environment REDUCED the interference of the matrices and ALLOWED to perform the analysis with good precision and accuracy. In case #1, analysis showed a blood cyanide concentration of 0.99 μg/ml. In case #2, cyanide concentrations were 1.3 μg/g in brain, 0.8 μg/g in lung, 1.6 μg/g in liver, and 1.2 μg/g in gastric content. The cyanide concentrations found in the two reported cases have been suitable to cause death by poisoning.

Origami paper analytical assay based on metal complex sensor for rapid determination of blood cyanide concentration in fire survivors

Cyanide-based blood poisoning can seriously damage fire victims and cause death if not detected quickly. Previous conventional methods require laboratory equipment, which are expensive and increase the duration of the analysis. Here, a simple origami based microfluidic device was introduced for point of need detection of blood cyanide concentration in people involved in fire. The device is made of four layers of paper. Each layer was in the size of 1 × 1 cm folded on each other. In this work, the blood sample was acidified by trichloroacetic acid to separate cyanide from methaemoglobin in the form of HCN gas. The produced gas released into borate buffer to recover free cyanide ions which interacted with the Pt complex ([Pt(p-MeC6H4)2(phen)]) used as a receptor in this study. Optimized conditions were applied to have a suitable interaction causing the color of the receptor to change from yellow to colorless. The color changes were recorded by a smartphone, and the sensor response was calculated by the routine image analysis software. The assay was capable of determining cyanide ions at different concentrations in the range of 1.0 to 100.0 µmol L−1. The detection limit of these determination was equal to 0.4 µmol L−1. The assay responses were not affected by the interfering species. As a practical analysis, the proposed sensor was applied to determine cyanide ions in the blood sample of 20 studied fire survivors and 10 controls with high accuracy.

A new chemosensor for cyanide in blood based on the Pd complex of 2-(5-bromo-2-pyridylazo)-5-[N-n-propyl-N-(3-sulfopropyl)amino]phenol.

A new indirect chemosensor for the detection of cyanide in blood is developed. 2-(5-Bromo-2-pyridylazo)-5-[N-n-propyl-N-(3-sulfopropyl)amino]phenol, a yellow dye, forms a blue-coloured complex with palladium ions. The yellow colour of this complex is regained upon reaction with cyanide ions. The complex shows high selectivity for the detection of cyanide over 16 other anions. The system was applied to two different methods for the detection of cyanide in human whole blood. As a quantitative absorbance method, blood samples were mixed with acid, and the resulting vaporised hydrogen cyanide was absorbed in an alkaline solution containing the complex in a Conway cell. The resulting absorbance response of the solution at 450 nm is linear over the range 4-40 μM (R2 = 1.000), and the limit of detection is 0.6 μM. Furthermore, the complex-soaked paper is applicable as a test strip for cyanide detection. When a test strip is used with 0.5 mL of blood, the limit of detection is 15 μM. The detection limits of these two methods are below the toxic blood cyanide concentration (19 μM). Therefore, both methods allow the quantification and screening of cyanide in blood samples. Furthermore, the test strip is low cost and enables on-site analysis.

Cyanide concentrations in blood and tissues of fire victims.

Cyanide poisoning has been regarded to contribute the fatal outcome in fire victims. The toxicity of inhaled hydrogen cyanide (HCN) at the cellular level was evaluated considering the impact of methemoglobin (MetHb) produced by fire gases. Cyanide (CN) concentrations and total hemoglobin contents were measured in right heart blood (RHB) and seven organs/tissues (basal ganglia, brain stem, heart, lung, liver, kidney and psoas muscle) collected from 20 fire fatalities. MetHb and carboxyhemoglobin saturations were also measured in RHB. The amount of CN probably bound to the cytochrome c oxidase of the tissue cells (CCO-CN) was extrapolated from CN and hemoglobin contents in RHB and organs/tissues, MetHb saturation in RHB and binding capacity of MetHb for CN. CN concentrations in RHB showed a wide range with the highest concentration of 8.927 μg/mL. The lung contained the largest CN content among organs/tissues with the mean concentration of 2.219 μg/g, then the heart (0.259 μg/g) and it was lower than 0.100 μg/g in others. Exceedingly large amount of CN in the lung could be explained by high hemoglobin content, being the port of entry of HCN and postmortem diffusion of fire gases. CCO-CN was theoretically present in about 20% of organ/tissue samples, most commonly in the basal ganglia (10 samples, with the mean of 0.059 μg/g) followed by heart (eight samples, with the mean of 0.109 μg/g). No CCO-CN was found in liver and kidney. HCN might have the effect on brain and heart.

Ground Flaxseed – How Safe is it for Companion Animals and for Us?

EFSA released the 89-page Scientific Opinion “Evaluation of the health risks related to the presence of cyanogenic glycosides in foods other than raw apricot kernels”. This opinion, and the ensuring media coverage, has left uncertainty in the minds of consumers, feed and supplement manufacturers and flaxseed producers of how much ground flaxseed can safely be consumed without crossing the threshold of cyanide toxicity. This editorial updates the science and tries to bring clarity to the question “how much flaxseed can I safely feed my dog, cat, horse on a daily basis?” and “how much can I safely eat?” The great majority of ground flaxseed products have a cyanogenic glycoside content of less than 200 mg / kg seed. For people, consuming 30 grams of such flaxseed the average peak blood cyanide concentration will be about 5 µmole / L, much less than the toxic threshold value of 20 to 40 µmole / L favoured by EFSA. Thus, as much as 120 grams of crushed / ground flaxseed can be consumed by a 70 kg adult person before a toxic threshold of 40 µmole / L is reached (up to 1.7 grams ground flaxseed / kg body weight). The toxic threshold of cyanide for dogs is 2 to 4-fold greater than for humans, and unknown for cats and horses. The daily serving amounts for dogs and cats are about 0.23 grams / kg body mass per day, which will result in blood cyanide well below the toxic threshold. The highest recommended daily serving amount for horses is 454 grams per day, or 0.8 to 2 grams per kg / body mass depending on mass of the horse. This amount for horses should not be exceeded.

The relationship between the intramuscular bleeding of the tongue and cause of death

Intramuscular bleeding of the tongue (ImBT) is occasionally found during post mortem examination. Despite its frequent reports, its cause has not yet been clarified. In this study, forensic autopsy data of 799 cadavers were examined and the relationship between ImBT and cause of death was investigated. A total of 74 cases showed ImBT (16 of 66 cases of fire fatality, 17 of 108 cases of drowning, 23 of 74 cases of asphyxiation, and 18 of 551 cases of other causes of death). The frequency of bleeding was significantly greater in cases with causes of death including fire fatality, drowning, and asphyxiation compared to those with other causes of death (p < 0.01). Among asphyxiation cases, ImBT was confirmed in two of five cases of typical hanging, three of 16 cases of atypical hanging, six of six cases of ligature strangulation, two of two cases of manual strangulation, eight of 38 cases of airway obstruction, and two of seven cases of oxygen deficiency. Among fire fatalities, the carboxyhemoglobin (CO-Hb) concentration of cases with ImBT was significantly lower than that in cases without ImBT (p < 0.01). In addition, the frequency of bleeding was significantly higher (p < 0.05) in cases where the blood cyanide concentration was 0.05 ppm or less. These observations suggested that ImBT during fire fatality occurs in a manner similar to that of ligature or manual strangulation, in which the flames cause the contraction and decrease in elasticity of the skin. Past reports indicated that bleeding frequency in cases of drowning did not significantly differ from that in cases with other causes of death. However, our cases showed a statistically higher incidence of bleeding compared to that in the other causes of death (p < 0.01).These results suggested that ImBT is a characteristic finding in cases of asphyxia and is an important evaluation for the diagnosis of death. When the relationship between ImBT and petechial hemorrhage was examined in three of the causes of death, no significant difference was observed between fire fatality and asphyxiation, but drowning was significantly different (p < 0.05). In cases without ImBT, the secretion of noradrenaline and adrenaline was significantly higher (p < 0.01). This finding suggests that it is unlikely that excessive secretion of catecholamine causes ImBT.

Improved ninhydrin-based reagent for spectrophotometric determination of ppb levels of cyanide

ABSTRACTCyanide is an extremely severe poison that has been raising concerns and controversies regarding its toxic effects on humans and the environment. A short-term human exposure to elevated levels can induce coma or death. Toxic effects occur at blood cyanide concentrations of 0.05 mg/dL, while death can occur at levels of 0.3 mg/dL. Numerous law and systems regulate cyanide levels in various environments. To exemplify, the maximum contamination limit imposed by United States Environmental Protection Agency in drinking water is 200 µg/L, while the European Union presents a lower limit of 50 µg/L. Ninhydrin has proved to be an effective color reagent for the spectrophotometric determination of trace levels of cyanide. This article reports a ninhydrin-based color reagent that was employed in cyanide determination involving real samples of water, cigarette smoke, urine, and cyanogenic plants, achieving an appropriate sample pretreatment procedure for cyanide liberation and separation. The reaction between cyanide and ninhydrin is fast enough to be performed at ambient conditions, but the ninhydrin reagent must be freshly prepared in oxygen-free solvent. Beer's law is obeyed in the range between 20 and 400 ppb CN− (r = 0.992; N = 7) with molar absorptivity of 1.4 × 105 L mol−1 cm−1 and limit of detection of 8 ppb cyanide. Recovery at 100 ppb CN− was (100.5 ± 0.1) %, whereas precision was 1.7%. Also, absorbance at 485 nm proved to be temperature-dependent, with a maximum at ambient conditions. Throughout all measurements, the ninhydrin-based assay proved to be reliable, economical and environmentally friendly. Significance of the assay for the determination of cyanide in the field of environmental forensics, as well as its potential aid in elucidating incidents with legal consequences are highlighted.

Intravenous Cobinamide Versus Hydroxocobalamin for Acute Treatment of Severe Cyanide Poisoning in a Swine (Sus scrofa) Model

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.

Combined administration of hyperbaric oxygen and hydroxocobalamin improves cerebral metabolism after acute cyanide poisoning in rats

Hyperbaric oxygen therapy (HBOT) or intravenous hydroxocobalamin (OHCob) both abolish cyanide (CN)-induced surges in interstitial brain lactate and glucose concentrations. HBOT has been shown to induce a delayed increase in whole blood CN concentrations, whereas OHCob may act as an intravascular CN scavenger. Additionally, HBOT may prevent respiratory distress and restore blood pressure during CN intoxication, an effect not seen with OHCob administration. In this report, we evaluated the combined effects of HBOT and OHCob on interstitial lactate, glucose, and glycerol concentrations as well as lactate-to-pyruvate ratio in rat brain by means of microdialysis during acute CN poisoning. Anesthetized rats were allocated to three groups: 1) vehicle (1.2 ml isotonic NaCl intra-arterially); 2) potassium CN (5.4 mg/kg intra-arterially); 3) potassium CN, OHCob (100 mg/kg intra-arterially) and subsequent HBOT (284 kPa in 90 min). OHCob and HBOT significantly attenuated the acute surges in interstitial cerebral lactate, glucose, and glycerol concentrations compared with the intoxicated rats given no treatment. Furthermore, the combined treatment resulted in consistent low lactate, glucose, and glycerol concentrations, as well as in low lactate-to-pyruvate ratios compared with CN intoxicated controls. In rats receiving OHCob and HBOT, respiration improved and cyanosis disappeared, with subsequent stabilization of mean arterial blood pressure. The present findings indicate that a combined administration of OHCob and HBOT has a beneficial and persistent effect on the cerebral metabolism during CN intoxication.

Report on a study of fires with smoke gas development

This is a report on an international non-interventional study of patients exposed to fires with smoke development in closed rooms. The objective of the study was to document clinical symptoms, relevant laboratory values and blood cyanide concentrations from fire victims in order to confirm or rule out presumptive correlations between the individual parameters. The study was conducted in five European countries with patients being included if they presented with the characteristic clinical signs, such as soot deposits and altered neurological status. Venous blood samples were taken from victims prior to administration of an antidote in all cases and determination of cyanide concentration was performed in a central laboratory using high performance liquid chromatography. Data from 102 patients (62 % male, average age 49 years) were included in the evaluation with no blood samples being available for analysis from 2 patients. In 25 patients the blood cyanide concentration was below the limit of detection of 1.2 μmol/l. Cyanide levels between 1.2 and 10 μmol/l were measured in 54 patients, 7 patients had values between 10 and 20 μmol/l, 4 patients between 20 and 40 μmol/l while levels above 40 μmol/l were determined in 10 patients. The results of the study could not demonstrate that the cyanide level was influenced either by the interval between smoke exposure and blood sampling or the duration presence at the fire scene. The following clinical signs or laboratory values were recorded as relevant for increased and possibly toxic cyanide levels: respiratory arrest, dyspnea, resuscitation requirement, tracheal intubation, respiratory support measures, low Glasgow coma scale (GCS) score and respiratory frequency. A correlation between cyanide concentration and the total amount of soot deposits on the face and neck, in the oral cavity and in expectoration was confirmed. A correlation between cyanide and carboxyhemoglobin (COHb) levels in the blood of fire victims was also confirmed. As long as it is not possible to immediately determine the blood cyanide concentration in patients exposed to fire with smoke development, a decreased GCS score, soot deposits particularly in expectoration, dyspnea and convulsions are to be regarded as risk markers for intoxication. In their presence immediate administration of hydroxocobalamin as an antidote is recommended.

Comparison of a New Cobinamide-Based Method to a Standard Laboratory Method for Measuring Cyanide in Human Blood

Most hospital laboratories do not measure blood cyanide concentrations, and samples must be sent to reference laboratories. A simple method is needed for measuring cyanide in hospitals. The authors previously developed a method to quantify cyanide based on the high binding affinity of the vitamin B12 analog, cobinamide, for cyanide and a major spectral change observed for cyanide-bound cobinamide. This method is now validated in human blood, and the findings include a mean inter-assay accuracy of 99.1%, precision of 8.75% and a lower limit of quantification of 3.27 µM cyanide. The method was applied to blood samples from children treated with sodium nitroprusside and it yielded measurable results in 88 of 172 samples (51%), whereas the reference laboratory yielded results in only 19 samples (11%). In all 19 samples, the cobinamide-based method also yielded measurable results. The two methods showed reasonable agreement when analyzed by linear regression, but not when analyzed by a standard error of the estimate or paired t-test. Differences in results between the two methods may be because samples were assayed at different times on different sample types. The cobinamide-based method is applicable to human blood, and can be used in hospital laboratories and emergency rooms.

The effect of sodium fluoride on the stability of cyanide in postmortem blood samples from fire victims

Assigning a level of significance to cyanide concentrations found in the blood of fire victims is often hampered by the fact that cyanide is inherently unstable in cadavers and in stored blood samples. A few researchers have proposed that sodium fluoride can be used to minimize the instability of cyanide in blood samples; however, controlled studies have not been performed to support validation of this hypothesis. To test the sodium fluoride hypothesis, both treated and control blood samples from 14 autopsied fire victims were tested over a 25–30 day period. A 2% concentration of sodium fluoride was added to the blood samples at the start of testing and the samples were refrigerated between testing intervals. Cyanide concentrations in the treated and control samples were measured between 9 and 11 days post treatment and between 25 and 30 days post treatment. A statistically significant difference was not present between blood cyanide concentrations in treated and control samples between 9 and 11 days. During this time period, although there were small statistically significant increases in both treated and untreated samples the fluctuations were minor. Since the treated and control samples did not exhibit instability between 9 and 11 days, it is not surprising that the sodium fluoride appeared to have no effect. However, a statistically significant difference between blood cyanide concentrations in treated and control samples was observed between 25 and 30 days. Those samples treated with sodium fluoride showed a reduction in blood cyanide variability with virtually no overall change, over a 25–30 day period when compared to control samples, while unconditioned samples showed a significant, average increase of 35%.

The effect of sodium fluoride on the stability of cyanide in postmortem blood samples from fire victims

Assigning a level of significance to cyanide concentrations found in the blood of fire victims is often hampered by the fact that cyanide is inherently unstable in cadavers and in stored blood samples. A few researchers have proposed that sodium fluoride can be used to minimize the instability of cyanide in blood samples; however, controlled studies have not been performed to support validation of this hypothesis. To test the sodium fluoride hypothesis, both treated and control blood samples from 14 autopsied fire victims were tested over a 25-30 day period. A 2% concentration of sodium fluoride was added to the blood samples at the start of testing and the samples were refrigerated between testing intervals. Cyanide concentrations in the treated and control samples were measured between 9 and 11 days post treatment and between 25 and 30 days post treatment. A statistically significant difference was not present between blood cyanide concentrations in treated and control samples between 9 and 11 days. During this time period, although there were small statistically significant increases in both treated and untreated samples the fluctuations were minor. Since the treated and control samples did not exhibit instability between 9 and 11 days, it is not surprising that the sodium fluoride appeared to have no effect. However, a statistically significant difference between blood cyanide concentrations in treated and control samples was observed between 25 and 30 days. Those samples treated with sodium fluoride showed a reduction in blood cyanide variability with virtually no overall change, over a 25-30 day period when compared to control samples, while unconditioned samples showed a significant, average increase of 35%. Based on the findings of this study, it is recommended that 2% sodium fluoride be added to blood samples obtained from fire victims to reduce cyanide instability due to bacteriological activity.

An unusual cause of severe lactic acidosis: cyanide poisoning after bitter almond ingestion

Dear Editor, Although cyanide exists in various alimentary sources like manioc, corn, bitter almonds, peach or apricot kernels, food-related cyanide intoxications are rare [1]. A 58-year-old healthy woman was admitted for sudden headaches, dizziness, vomiting, and generalized seizures. Prehospital medical services found her comatose (Glasgow Coma Score: 5) with bradycardia (30/min) and nonmeasurable blood pressure. She was promptly intubated and received fluids. A brain CT scan was normal. On intensive care unit (ICU) admission, her blood pressure was 80/40 mmHg, heart rate 62/min, SpO2 100% (FiO2: 100%), and temperature 37.0 C. Physical examination, electrocardiogram, and echocardiography were unremarkable. Severe lactic acidosis (arterial pH: 6.59, base deficit: 36.0 mmol/l, anion gap: 33.0 mmol/l, and plasma lactate concentration: 26.0 mmol/l) was assessed without ketosis, osmolar gap, liver or renal dysfunction. Fluids (2,000 ml), norepinephrine (0.5 mg/h), insulin, and sodium bicarbonate were infused. Routine toxicological screening was negative. Blood cyanide concentration was 2.77 mg/l (spectrophotometric method; N \0.2 mg/l; limit of detection: 0.06 mg/l) 6 h after coma onset. Hydroxocobalamin (10 g, 140 mg/kg) was immediately infused, resulting in complete recovery: lactate normalization (within 12 h, Table 1), norepinephrine weaning (20 h), acid/base balance correction (36 h), extubation (day 2), and ICU discharge (day 3). Her husband finally remembered that she had ingested a large quantity of bitter almonds (around 50) from the garden, 2 h before symptom onset. Accidental food-related cyanide poisonings are unusual [1]. Signs are delayed after ingestion, in relation to enzymatic processes producing cyanide in the gut from the ingested cyanogenic glucosides. Cyanide poisoning is rapidly fatal if not promptly treated. Clinical features are not specific, misleading the diagnosis. However, when suspicion is based on compatible circumstances, plasma lactate concentrations C8 mmol/l are an excellent predictor of blood cyanide concentrations C1 mg/l [2]. In our case, despite no relevant anamnesis, cyanide poisoning was suspected because of severe lactic acidosis with coma, hypotension, and bradycardia in the absence of sepsis. Reported symptoms of cyanide poisoning following almond/seed ingestion included headaches, dizziness, sweating, pink cyanosis, coma, seizures, hyperthermia, hypotension, polypnea, bradypnea, hypoglycemia, and lactic acidosis [3, 4]. To our knowledge, hyperlactatemia (pH 7.17, lactate: 14.3 mmol/l) was reported in only one case after ingestion of bitter almonds with laetrile tablets (containing amygdaline) given for alternative cancer treatment [3]. The present case is unique for two reasons: the severity of almondinduced lactic acidosis and its dramatic improvement after hydroxocobalamin infusion. Management of cyanide poisoning is based on advanced life support and antidotes. Despite cyanide-induced deficient cell oxygen utilization, increased oxygen delivery (FiO2: 100%) is useful to reactivate mitochondrial enzymes and other oxidative systems. Hydroxocobalamin is an effective and safe antidote binding cyanide on an equimolar ratio to form stable cyanocobalamin, which is excreted in urine [5]. Although we should

Effect of Hyperbaric Oxygen Therapy on whole blood cyanide concentrations in carbon monoxide intoxicated patients from fire accidents

BackgroundHydrogen 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.ObjectiveThe purpose of the present study was to determine whole blood CN concentrations in fire victims before and after HBO treatment.Materials and methodsThe 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.ResultsThe 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 ConclusionCN 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 RegistrationClinicalTrials.gov identifier: NCT00280579

Toxicological responses in SW mice exposed to inhaled pyrolysates of polymer/tobacco mixtures and blended tobacco

Modern cigarette manufacturing is highly automated and produces millions of cigarettes per day. The potential for small inclusions of non-cigarette materials such as wood, cardboard packaging, plastic, and other materials exists as a result of bulk handling and high-speed processing of tobacco. Many non-tobacco inclusions such as wood, paper, and cardboard would be expected to yield similar pyrolysis products as a burning cigarette. The aircraft industry has developed an extensive literature on the pyrolysis products of plastics, however, that have been reported to yield toxic by-products upon burning, by-products that have been lethal in animals and humans upon acute exposure under some exposure conditions. Some of these smoke constituents have also been reported in cigarette smoke. Five synthetic polymers, nylon 6, acrylonitrile–butadiene–styrene (ABS), nylon 12, nylon 6,6, and acrylonitrile–butadiene (AB), and the natural polymer wool were evaluated by adding them to tobacco at a 3, 10, and 30% inclusion level and then pyrolyzing the mixture. The validated smoke generation and exposure system have been described previously. We used the DIN 53-436 tube furnace and nose-only exposure chamber in combination to conduct exposures in Swiss-Webster mice. Potentially useful biological endpoints for predicting hazards in humans included sensory irritation and pulmonary irritation, respiratory function, clinical signs, body weights, bronchoalveolar lavage (BAL) fluid analysis, carboxyhemoglogin, blood cyanide concentrations, and histopathology of the respiratory tract. Chemical analysis of selected smoke constituents in the test atmosphere was also performed in order to compare the toxicological responses with exposure to the test atmospheres. Under the conditions of these studies, biological responses considered relevant and useful for prediction of effects in humans were found for sensory irritation, body weights, BAL fluid analysis, and histopathology of the nose. There was a marked sensory irritation response that recovered slowly for some polymers. Sustained body weight depression, lesions of the respiratory epithelium of the nose, and morphological changes in pulmonary alveolar macrophages (PAM) were observed after exposure to some polymer/tobacco pyrolysates. These responses were increased compared to exposure to tobacco pyrolysate alone. No moribundity or mortality occurred during the study. The data suggest that polymeric inclusions pose a minimal additional toxicologic hazard in humans.

Cyanide poisoning in Taiwan

In May, 2005, a 32-year-old woman lost consciousness soon after drinking a non-alcoholic beverage. She was transported to hospital within 5 min, found to be unresponsive, and intubated. Before intubation, blood gas measurements on room air (possible venous sample), were: pH 7·846, pCO2 24·2 mm Hg, pO2 28·7 mm Hg, HCO3 41·8 mmol/L (base excess [BE] 26 mmol/L); O2 saturation was 79·4%. The beverage had a pH of 9; a working diagnosis of alkaline corrosive injury was made, and she was transferred to our emergency unit. When seen by us, about 1 h after poisoning, her blood pressure was 85/46 mm Hg, despite norepinephrine 8 μg/min; blood gases (on ventilator with 100% oxygen; O2 saturation 100%) pointed to metabolic acidosis: pH 7·096, pCO2 17·2 mm Hg, pO2 385 mm Hg, HCO3 5·4 mmol/L (BE –21·7 mmol/L); blood lactate concentration was 14 mmol/L. The anion gap was 37·6 mmol/L. Cyanide (CN) poisoning was suspected and 2·5 g intravenous hydroxocobalamine was given. Our patient showed signs of improvement 2–3 min after antidote, but a second dose was given 1 h later because of persistent severe metabolic acidosis. She continued to improve, regained consciousness, and was extubated the next morning. Her blood CN concentration on transfer to us was 288·6 μmol/L; her drink had been laced with 1·9% (fi nal concentration in the beverage) potassium cyanide (KCN). The patient was discharged 10 days later; when last seen in 2007, she was well. On May 17, 2005, over ten bottles of a non-alcoholic beverage were spiked with KCN in various convenience stores in Taiwan. Our patient was the fi rst of three people who were poisoned and who collapsed soon after consuming a small amount of the drink. Blood gas data are shown in the fi gure. Even accounting for the change in CO2 as a result of respiratory compensation, and the possible venous sample, the large change in HCO3 from A to B is probably due to huge acid production —typical of CN poisoning. The initial alkalosis seen in our patient could have been due to various factors. The pKa of KCN is 9·21 at 25°C. When it is given orally, the gastric acid environment favours formation of the unionised form of HCN and facilitates HCN absorption across the gastrointestinal mucosa. Initially, the absorbed HCN, particularly with smaller doses, stimulates central nervous system driven hyperventilation, leading to respiratory alkalosis (supported by blood gas data from the second case—not shown). In a pure respiratory alkalosis, we would have expected our patient’s blood pCO2 to be less than 10 mm Hg, given that pH was 7·846. It is possible that HCO3 formation in the stomach could have contributed to our patient’s initially raised blood pCO2. In the stomach, HCl is depleted in gastric secretions because it reacts with KCN. Each mmol of H secreted will generate 1 mmol of HCO3, leading to a transient increase in plasma HCO3. In KCN ingestion, there is no stimulus for HCO3 secretion in the duodenum because of gastric acid depletion and quick absorption of HCN. The net result is an increase in plasma HCO3 concentration. Severe metabolic acidosis, with raised lactate, occurred quickly, because KCN inhibits the electron transport chain and anaerobic respiration. Hydroxocobalamine 5–10 g is the recommended treatment. We gave our patient an initial dose of 2·5 g hydroxocobalamine because of the potential for mass casualties and low stores of antidote. Only prompt diagnosis and antidote can resolve severe CN poisoning.

Hydroxocobalamin (vit b12a) effectively reduced extent of cyanide poisoning arising from oral amygdalin ingestion in rats

This study investigated the efficacy of hydroxocobalamin in reducing cyanide toxicity arising from amygdalin administration in rats. Amygdalin at its therapeutic dose (20 mg/kg body weight) was co-administered with hydroxocobalamin to rats at two different levels (25 mg/kg and 50 mg/kg body weight) for 14 days. Symptoms of cyanide toxicity in the blood and liver were monitored in the animals and compared with the control. One of the rats who received amygdalin without the antidote died of cyanide poisoning before the end of the experimental period while no mortality was recorded in rats who received the antidote. There was significant reduction (P < 0.05) in blood cyanide and serum lactate concentration in a dose-dependent manner in rats who received the antidote compared with the control. Blood of rats fed amygdalin showed significant elevation in packed cell volume (PCV) and haemoglobin concentration accompanied with significant reduction in blood pH while these abnormalities were reversed by hydroxocobalamin. Histological studies of the liver of amygdalin-fed rats revealed marked alteration in cellular architecture which was not noticeable in rats who received the antidote. We conclude that rats can be protected from the deleterious effects of cyanide poisoning due to amygdalin ingestion by the concomitant administration of hydroxocobalamin. Key words: Amygdalin, antidote, hydroxocobalamin, cyanide toxicity.

Evaluation of a novel inhalation exposure system to determine acute respiratory responses to tobacco and polymer pyrolysate mixtures in Swiss-Webster mice

Modern cigarette production processes are highly automated and yield millions of cigarettes per day. The forming cigarette and its components contact many different materials in the production process, some of which may leave minute residues. The potential for small inclusions of non-cigarette materials such as wood, plastic, cardboard and other materials exists from the bulk handling and processing of tobacco, in spite of vigilant workers and numerous online systems designed to keep the tobacco stream clean. Currently, there are no published methods that describe an approach to evaluate the potential toxicological impact of these non-tobacco residues and inclusions on the biological activity from exposure to the complex mixture of tobacco smoke. There are, however, many methods which describe toxicological evaluation approaches for pure materials, particularly synthetic polymers. We used the Deutsche Institute fur Normung (DIN) 53-436 tube furnace and nose-only exposure chamber in combination to conduct pilot studies in Swiss-Webster mice in order to develop a standardized methodology for the evaluation of sensory irritation and other potentially useful biological endpoints for predicting any potential hazards. Sensory and/or pulmonary irritation was assessed based on respiratory function parameters using the ASTM E981-84 method described by in mice, exposed to test atmospheres of 100% tobacco pyrolysate or tobacco/polymer pyrolysate mixtures. Other biological evaluations included respiratory function parameters, clinical signs, body weights, bronchoalveolar lavage fluid analysis, carboxyhemoglobin, blood cyanide concentrations and histopathology of the respiratory tract. These pilot studies have demonstrated that such an approach can detect biological changes resulting from exposure to unique tobacco/polymer pyrolysates. Small differences were detected in the sensory irritation responses (respiratory function), activation state of pulmonary macrophages, and histopathological findings in the nose of mice exposed to 100% tobacco or tobacco/polymer pyrolysates. Analytical measurements were also performed in order to characterize the test atmospheric changes that could occur from inclusion of the polymer into the tobacco. These included DIN-generated wet total particulate matter (TPM) DIN-Generated wet TPM (DWTPM), nicotine, cyanide, formaldehyde, acetaldehyde, acrolein, carbon monoxide, carbon dioxide, and nitrogen oxides. We attempted to correlate analyte differences in the test atmospheres with the resulting biological findings in the mice. The results demonstrated that this approach could detect minimal toxicological effects in mice exposed to test atmospheres of 100% tobacco or 70%/30% tobacco/polymer pyrolysates.

Rapid and sensitive headspace gas chromatographic method for cyanide determination in whole blood

We reported a simple and rapid headspace (HS) gas chromatographic (GC) assay for the determination of cyanide in human whole blood obtained from both cadaveric and intoxicated subjects. The poison was extracted from whole blood samples by HS technique after 10 min incubation at 80°C with a HCl (1N) acidic solution supplemented with 30 g L−1 of sodium chloride and 10 mg L−1 of isopropanol as internal standard. A SGE WAX capillary column (30 m × 0.32 mm ID × 0.5 µm df) was used. The Flame Ionization Detector (FID) was set at 250°C. The detection and the quantification limits were 0.02 and 0.2 mg L−1, respectively. In the within-day study, the coefficients of variation for three different whole blood cyanide concentrations varied between 3.2 and 6.5%, whereas those in the day-to-day study varied between 4.8 and 6.3%. The assay was performed in less than 20 min per sample, which appears to be suitable for emergency toxicological tasks involved in diagnosis of cyanide poisoning.