Blood Cyanide Levels Research Articles

Modification of sensitive pyridine-pyrazolone method for determination of blood cyanide and its possible applications in fatal aircraft accidents

BackgroundFatal aviation accidents are a critical concern for armed forces, necessitating precise toxicological analysis of postmortem blood samples. This paper introduces a novel spectrophotometric method for quantifying cyanide in blood samples with an aim to aid in aircraft accident reconstruction in the future. MethodsBlood samples were collected from healthy non-smokers aged 20–45 years, excluding individuals with hepatic impairment, or those using drugs affecting blood cyanide levels. The spectrophotometric method involved cyanide adsorption in a sodium hydroxide solution using microdiffusion discs and chemical reactions resulting in a pinkish-purple end product. The optimal absorption wavelength (λmax) was determined, and the lower limits of detection and quantitation were established. The method underwent validation for precision, sensitivity, specificity, linearity, and accuracy. ResultsThe procedure yielded a pinkish-purple compound with an optimal absorption wavelength (λmax) of 531 nm. The established limits of detection (LoD) and quantitation (LoQ) were 0.0625 μg/ml and 0.125 μg/ml, respectively. The method demonstrated strong linearity up to cyanide concentrations of 4 μg/ml. It exhibited a sensitivity of 99.7% and accuracy of 85.92%. The intraday and inter-day precision were determined as 9.04% and 4.27%, respectively. The method was highly specific, showing no interference with blanks at the peak wavelength with a working range of 0.125–4 μg/ml. ConclusionThe study describes developing and validating a sensitive method for quantitatively estimating cyanide in blood samples. Incorporating this method into the existing postmortem toxicological sample collection and investigation protocol will enhance the analysis capabilities and improve aircraft accident investigation outcomes within the country.

Compensatory Mechanism of Diet Containing Sulphur-Rich Amino Acids in Restoring Neurotoxico-Nutritional Deficits in Konzo Disease Rat Model

Introduction: The present study is aimed at assessing the effect of bitter cassava on blood biochemical parameters of konzo disease induced Wistar rats. Nutritional modification with suphur rich amino acids was used as a measure to correct the impact in rats induced konzo disease. Method: 25 adult male wistar rats were assigned to 5 experimental groups (i) Control n=5, (ii) cassava only n=5, (iii) cassava + animal feed n=5, (iv) cassava + Eggshell + Brown beans n=5, (v) Eggshell + Brown Beans only n=5. The bitter cassava foods were taken by oral ingestion for a period of 4 weeks. The weights of the rats were checked through the experiment and blood samples were taken from each group into EDTA-lined containers and analyses for blood cyanide, methionine and cysteine levels.
 Results: There was significant difference in weight and there was a progressive increase in their success rate as against the cassava only group which decreased in their success rate, hence, differs statistically and significantly (p˂0.05) from the control group. It was observed that the cassava fed group had higher blood level of cyanide far above the normal blood reference range (2.60 – 2.90µg/ml) for cyanides, hence, was seen to be statistically significant as compared to that of the control group. The eggshell and brown beans only group showed high blood levels of methionine that statistically differ significantly (p<0.05) from both the control group and the cassava only group. Blood level of cysteine in the cassava plus eggshell and brown beans group differed significant statistically from the control group.
 Conclusion: Sulphur amino acids such as methionine and cysteine are essential for detoxification of the residual cyanogens remaining in insufficiently processed cassava roots. Foods such as cereals and legumes as source of sulphur amino acids should be promoted to prevent paralytic neurotoxico-nutritional disease such as konzo among the poor population.

Human continuous hydrogen cyanide inhalation predictor with a physiologically based pharmacokinetic (PBPK) model.

Hydrogen cyanide (HCN) is volatile and highly toxic with acute and chronic effects on humans. Gaseous HCN enters the atmosphere from natural processes or industrial activities, which lead to human exposure. Effective intervention in cases of HCN inhalation requires an efficient diagnostic tool. The existing physiologically based pharmacokinetic (PBPK) model for HCN cannot clearly simulate continuous HCN inhalation or predict HCN levels in inhaled air. The current study presents a PBPK model for continuous inhalation of HCN, called Human Continuous Cyanide Inhalation Predictor (HCCIP). Since existing data on pharmacokinetics of HCN inhalation are limited, HCCIP utilizes extensive data from the current authors' PBPK model on cyanide ingestion. The structure of HCCIP comprises the lungs, kidneys, liver, and slowly perfused tissue. In both the human body and in exhaled air, HCCIP features the ability to predict concentration-time courses of cyanide. Moreover, HCCIP can predict HCN concentration in inhaled air from known blood cyanide levels. After completion, the results of HCCIP were validated against preexisting published datasets. The simulation results agreed with these datasets, validating the model. The HCCIP model is an effective tool for assessing risk from continuous HCN inhalation, and HCCIP extends the capabilities of air dispersion modeling, such as AERMOD or CALPUFF, to assess HCN risk from specific release sources.

Physiologically based pharmacokinetic modeling of hydrogen cyanide in humans following the oral administration of potassium cyanide and cyanogenic glycosides from food

Cyanogenic glycosides (CGs) are commonly found in some edible plants and seeds. After ingestion, CGs can release toxic hydrogen cyanide (HCN) in humans. At present, unfortunately, there is no tool capable of predicting the cyanide concentration in human blood and organs following oral administration of CG-containing food. The aim of this study was to develop a physiologically based pharmacokinetic (PBPK) model of cyanide following the ingestion of CG-containing food in humans. To develop this model, pharmacokinetic data concerning cyanide concentration levels in humans exposed to potassium cyanide (KCN) and CG-containing foods (persipan paste, linseed, cassava, and bitter apricot kernels) were obtained from published data. This study created a model structure consisting of four organ compartments including the lungs, kidneys, liver, and slowly perfused tissues by employing Berkeley Madonna software to extract three unknown parameters including the maximum velocity of rhodanese, the absorption rate constant, and the bioavailability for oral administration of KCN and the four CG-containing foods (equivalent a 6.8 mg dose of cyanide). The model was then validated by comparing the simulated results for the concentration-time courses of cyanide levels in venous blood with data from two clinical studies covering the oral administration of KCN and linseed at three other doses.

Chemical and Clinical Aspects of Metal-Containing Antidotes for Poisoning by Cyanide.

Physiological metabolism of cyanide takes place by a single major pathway that forms non-toxic thiocyanate that is subsequently excreted. Rhodanese is the primary enzyme to execute metabolism of cyanide with minor pathways from other sulfurtransferases in vivo. The rhodanese enzyme depends on sulfur donor availability to metabolize cyanide and poisoning occurs at elevated cyanide concentrations in vivo. Cyanide interacts with over 40 metalloenzymes, but its lethal action is non-competitive inhibition of cytochrome c oxidase, halting cellular respiration and causing hypoxic anoxia. Only a handful of antidotes for treatment of cyanide poisoning are known; they are primarily inorganic compounds and metal complexes which are intended to intercept cyanide before it inhibits cellular respiration. The inorganic compounds manipulate hemoglobin, forming methemoglobin, or supply sulfur for the rhodanese enzyme. The metal complexes intercept the cyanide and bind it before reaching its target. Cobalt complexes of corrins and vitamin B12 derivatives are the state-of-the-art agents, while the longest employed complex, Co2EDTA, is designed to deliver "free" cobalt for binding of cyanide. Compounds that are in development are discussed from the point of how they are designed to intercept cyanide. The challenge of reversing the cyanide inhibition of cytochrome c oxidase is based on the catalytic active site structure and reactivity. General information about history and occurrence of poisoning and clinical symptoms is discussed and the challenges related to analytical methods available to analyze blood cyanide levels and to confirm the presence of cyanide poisoning.

Determinants of Lactic Acidosis in Acute Cyanide Poisonings.

To investigate the magnitude of lactic acidosis in response to cyanide poisoning compared with the secondary response caused by cardiovascular shock. Retrospective case-control observational study. University Hospital of Assistance Publique - Hôpitaux de Paris. Patients admitted for suspicion of cyanide poisoning or drug overdose. Medical charts provided by Assistance Publique - Hôpitaux de Paris of patients between January 1988 and December 2015. None. Twelve cyanide poisoned patients were matched to 48 controls by age, sex, systolic blood pressure, catecholamine administration, and outcome at discharge from ICU. Extracted data included age, sex, vital signs, symptoms, biochemical parameters, toxicological analysis, treatment, and outcome. Non-parametric tests were used. Multivariable analysis was used to adjust for confounders causing hyperlactacidemia. The median blood lactate concentration was significantly greater in the cyanide group (15.6 mmol/L) compared to the control group (4.1 mmol/L; p = 0.0003). Similarly, blood lactate concentration greater than or equal to 8 mmol/l was observed in 83% of the cyanide cases versus 27% of the matched controls. Multivariate analysis conferred hyperlactacidemia as the lone factor which significantly predicted cyanide poisoning at an odds of 73.0 (5.7-936.1). Moreover, blood cyanide level significantly correlated with the increase of blood lactate (p = 0.0033). This study supports the hypothesis lactic acidosis primarily results from the direct toxicity of cyanide.

Cyanide poisoning is a possible cause of cardiac arrest among fire victims, and empiric antidote treatment may improve outcomes

BackgroundCarbon monoxide and cyanide poisoning are important causes of death due to fire. Carbon monoxide is more regularly assessed than cyanide at the site of burn or smoke inhalation treatment due to its ease in assessment and simplicity to treat. Although several forensic studies have demonstrated the significance of cyanide poisoning in fire victims using blood cyanide levels, the association between the cause of cardiac arrest and the concentration of cyanide among fire victims has not been sufficiently investigated. This study aimed to investigate the frequency of cyanide-induced cardiac arrest in fire victims and to assess the necessity of early empiric treatment for cyanide poisoning. MethodsThis study was a retrospective analysis of fire victims with cardiac arrest at the scene who were transported to a trauma and critical care center, Kyorin University Hospital, from January 2014 to June 2017. Patients whose concentration of cyanide was measured were included. ResultsFive patients were included in the study; all died despite cardiopulmonary resuscitation. Three of these victims were later found to have lethal cyanide levels (>3 μg/ml). Two of the patients had non-lethal carboxyhemoglobin levels under 50% and might have been saved if hydroxocobalamin had been administered during resuscitation. ConclusionAccording to our results, cyanide-induced cardiac arrest may be more frequently present among fire victims than previously believed, and early empiric treatment with hydroxocobalamin may improve outcomes for these victims in cases where cardiac arrest is of short duration.

Toxic smoke inhalation with cyanide: Correlation of blood cyanide and lactate levels in a pig model

Toxic smoke inhalation with cyanide: Correlation of blood cyanide and lactate levels in a pig model

Resuscitation after smoke inhalation with cyanide intoxication: Influence of hydroxycobalamin on the change of blood cyanide level during resuscitation

Resuscitation after smoke inhalation with cyanide intoxication: Influence of hydroxycobalamin on the change of blood cyanide level during resuscitation

Oral and intramuscular application of cyanogenic glycoside amygdalin did not induce changes in haematological profile of male rabbits

Amygdalin is a cyanogenic glycoside initially obtained from the seeds of bitter almonds. It is composed of one molecule of benzaldehyde, two molecules of glucose and one molecule of hydrocyanic acid. Various ways of amygdalin application play a different role in recipient organism. Intravenous infusion of amygdalin produced neither cyanidemia nor signs of toxicity, but oral administration resulted in significant blood cyanide levels. The present in vivo study was designed to reveal whether amygdalin is able to cause changes in the haematological profile and thus alter the physiological functions, using rabbits as a biological model. Adult male rabbits (n = 20) were randomly divided into five groups: the control group without any amygdalin administration, two experimental groups received a daily intramuscular injection of amygdalin at a dose 0.6 and 3.0 mg.kg-1 b.w. and other two groups were fed by crushed apricot seeds at dose 60 and 300 mg. kg-1 b.w., mixed with commercial feed over the period of 14 days. After two weeks, haematological parameters in whole blood were analysed (WBC - total white blood cell count, LYM - lymphocytes count, MID - medium size cell count, GRA - granulocytes count, RBC - red blood cell count, HGB - haemoglobin, HCT - haematocrit, MCV - mean corpuscular volume, MCH - mean corpuscular hemoglobin, MCHC - mean corpuscular hemoglobin concentration, RDWc - red cell distribution width, PLT - platelet count, PCT - platelet percentage, MPV - mean platelet volume, PDWc - platelet distribution width) using haematology analyser Abacus junior VET. Our findings indicate that intramuscular and oral application of amygdalin for two weeks did not significantly affect the haematology parameters in experimental animals. In this study, no obvious beneficial or negative effects of amygdalin administration on the blood of male rabbits were observed.

Acute health risks related to the presence of cyanogenic glycosides in raw apricot kernels and products derived from raw apricot kernels

Amygdalin is the major cyanogenic glycoside present in apricot kernels and is degraded to cyanide by chewing or grinding. Cyanide is of high acute toxicity in humans. The lethal dose is reported to be 0.5–3.5 mg/kg body weight (bw). An acute reference dose (ARfD) of 20 μg/kg bw was derived from an exposure of 0.105 mg/kg bw associated with a non-toxic blood cyanide level of 20 micro mol (μM), and applying an uncertainty factor of 1.5 to account for toxicokinetic and of 3.16 to account for toxicodynamic inter-individual differences. In the absence of consumption data and thus using highest intakes of kernels promoted (10 and 60 kernels/day for the general population and cancer patients, respectively), exposures exceeded the ARfD 17–413 and 3–71 times in toddlers and adults, respectively. The estimated maximum quantity of apricot kernels (or raw apricot material) that can be consumed without exceeding the ARfD is 0.06 and 0.37 g in toddlers and adults, respectively. Thus the ARfD would be exceeded already by consumption of one small kernel in toddlers, while adults could consume three small kernels. However, consumption of less than half of a large kernel could already exceed the ARfD in adults.

Environmental Health and Safety Hazards of Indigenous Small-Scale Gold Mining Using Cyanidation in the Philippines.

OBJECTIVESThis cross-sectional study aimed at the environmental health hazards at work and cyanide exposure of small-scale gold miners engaged in gold extraction from ores in a mining area in the Philippines.METHODSMethods consisted of structured questionnaire-guided interviews, work process observation tools, physical health assessment by medical doctors, and laboratory examination and blood cyanide determination in the blood samples of 34 indigenous small-scale gold miners from Benguet, Philippines.RESULTSThe small-scale gold miners worked for a mean of 10.3 years, had a mean age of 36 years, with mean lifetime mining work hours of 18,564. All were involved in tunneling work (100%) while a considerable number were involved in mixing cyanide with the ore (44%). A considerable number were injured (35%) during the mining activity, and an alarming number (35%) had elevated blood cyanide level. The most prevalent hazard was exposure to chemicals, particularly to cyanide and nitric acid, which were usually handled with bare hands.CONCLUSIONThe small-scale gold miners were exposed to occupational and environmental hazards at work.

Safety and efficacy of sodium nitroprusside during prolonged infusion in pediatric patients.

Sodium nitroprusside is a direct-acting vasodilator used to lower blood pressure in the operating room and ICU. The efficacy of sodium nitroprusside has been analyzed in few pediatric randomized trials. This study assesses the efficacy and safety of sodium nitroprusside following at least 12 hours of IV infusion in children. Randomized, double-blind withdrawal to placebo study. ICUs. Pediatric patients younger than 17 years. Following 12-24 hours of open-label sodium nitroprusside titration, a blinded infusion of sodium nitroprusside or placebo was administered (at the stable rate used at the end of the open-label phase) for up to 30 minutes. The primary efficacy measure was whether control of mean arterial blood pressure was lost, that is, increased above ambient baseline for two consecutive minutes during the blinded phase. The proportion of patients who lost mean arterial blood pressure control in the placebo group (15/19; 79%) was significantly different than those in the sodium nitroprusside group (9/20; 45%) (p = 0.048). Three patients experienced rebound hypertension during the blinded phase, and all were in the placebo group. Serious adverse event rates were low (7/52; 13%), and in only one patient was the serious adverse event determined to be related to sodium nitroprusside by the site investigator. Fourteen patients (27%) had whole blood cyanide levels above 0.5 μg/mL, with high correlation (0.7) between infusion rate and cyanide levels, but there were few clinical signs of cyanide toxicity. Sodium nitroprusside is efficacious in maintaining mean arterial blood pressure control in children following a 12-hour infusion. Although a high proportion of patients were found to have elevated cyanide levels, toxicity was not observed.

Hydroxocobalamin and Epinephrine Both Improve Survival in a Swine Model of Cyanide-Induced Cardiac Arrest

To determine whether hydroxocobalamin will improve survival compared with epinephrine and saline solution controls in a model of cyanide-induced cardiac arrest. Forty-five swine (38 to 42 kg) were tracheally intubated, anesthetized, and central venous and arterial continuous cardiovascular monitoring catheters were inserted. Potassium cyanide was infused until cardiac arrest developed, defined as mean arterial pressure less than 30 mm Hg. Animals were treated with standardized mechanical chest compressions and were randomly assigned to receive one of 3 intravenous bolus therapies: hydroxocobalamin, epinephrine, or saline solution (control). All animals were monitored for 60 minutes after cardiac arrest. Additional epinephrine infusions were used in all arms of the study after return of spontaneous circulation for systolic blood pressure less than 90 mm Hg. A sample size of 15 animals per group was determined according to a power of 80%, a survival difference of 0.5, and an α of 0.05. Repeated-measure ANOVA was used to determine statistically significant changes between groups over time. Baseline weight, time to arrest, and cyanide dose at cardiac arrest were similar in the 3 groups. Coronary perfusion pressures with chest compressions were greater than 15 mm Hg in both treatment groups indicating sufficient compression depth. Zero of 15 (95% confidence interval [CI] 0% to 25%) animals in the control group, 11 of 15 (73%; 95% CI 48% to 90%) in the hydroxocobalamin group, and 11 of 15 (73%; 95% CI 48% to 90%) in the epinephrine group survived to the conclusion of the study (P<.001). The proportion of animals with return of spontaneous circulation at 5 minutes was 4 of 15 (27%; 95% CI 10% to 52%), and that of return of spontaneous circulation at 10 minutes was 11 of 15 (73%; 95% CI 48% to 90%) in the 2 treatment groups. Additional epinephrine infusion after return of spontaneous circulation was administered for hypotension in 2 of 11 (18%; 95% CI 4% to 48%) hydroxocobalamin animals and in 11 of 11 (100%; 95% CI 70% to 100%) of the epinephrine animals (P<.001). At 60 minutes, serum lactate was significantly lower in the hydroxocobalamin group compared with the epinephrine group (4.9 [SD 2.2] versus 12.3 [SD 2.2] mmol/L), and the pH was significantly higher (7.34 [SD 0.03] versus 7.15 [SD 0.07]). Serial blood cyanide levels in the hydroxocobalamin group were also lower than that of the epinephrine group from cardiac arrest through the conclusion of the study. Intravenous hydroxocobalamin and epinephrine both independently improved survival compared with saline solution control in our swine model of cyanide-induced cardiac arrest. Hydroxocobalamin improved mean arterial pressure and pH, decreased blood lactate and cyanide levels, and decreased the use of rescue epinephrine therapy compared with that in the epinephrine group.

Cyanide Toxicity in Juvenile Pigs and Its Reversal by a New Prodrug, Sulfanegen Sodium

Cyanide (CN) toxicity is a serious clinical problem and can occur with sodium nitroprusside (SNP) administration, accidental smoke inhalation, industrial mishaps, and bio-terrorism. In this study, we induced severe CN toxicity independently with SNP or sodium cyanide (NaCN) in a juvenile pig model to demonstrate reversal of severe CN toxicity with a new antidote, sulfanegen sodium, a prodrug of 3-mercaptopyruvate. SNP study: A pilot study in 11 anesthetized, mechanically ventilated juvenile pigs allowed us to determine the dose of SNP to induce CN toxicity. Blood CN, serum lactates, and blood gases were monitored. CN toxicity was defined as the occurrence of severe lactic acidosis accompanied by significant elevation in blood CN levels. Based on this pilot study, 8 anesthetized pigs received a high-dose i.v. infusion of SNP (100 mg/h) for 2 hours to induce CN toxicity. They were then randomized to receive either sulfanegen sodium or placebo. Four pigs received 3 doses of sulfanegen sodium (2.5 g i.v.) every hour after induction of severe CN toxicity, and 4 pigs received placebo. NaCN study: A pilot study was conducted in 4 spontaneously ventilating pigs sedated with propofol plus ketamine to demonstrate hemodynamic and metabolic stability for several hours. After this, 6 pigs were similarly sedated and given NaCN in bolus aliquots to produce CN toxicity ultimately resulting in death. Hemodynamics and metabolic variables were followed to define peak CN toxicity. In another group of 6 pigs, severe CN toxicity was induced by this method, and at peak toxicity, the animals were given sulfanegen sodium (2.5 g i.v.) followed by a repeat dose 60 minutes later in surviving animals. SNP study: The pilot study demonstrated the occurrence of a significant increase in blood CN levels (P < 0.05) accompanied by severe lactic acidemia (P < 0.05) in all pigs receiving a high dose of SNP. Administration of the sulfanegen antidote resulted in progressive significant reduction in blood lactate and CN levels with 100% survival (P < 0.05), whereas the placebo-treated pigs deteriorated and did not survive (P < 0.05). NaCN study: NaCN injection resulted in CN toxicity accompanied by severe lactic acidosis and mortality in all the pigs. Sulfanegen sodium reversed this toxicity and prevented mortality in all the pigs treated with this antidote. CN toxicity can be successfully induced in a juvenile pig model with SNP or NaCN. The prodrug, sulfanegen sodium, is effective in reversing CN toxicity induced by SNP or NaCN.

Swedish forensic data 1992–2009 suggest hydrogen cyanide as an important cause of death in fire victims

Between 60 and 80% of all deaths related to fire are attributed to toxic fumes. Carbon monoxide (CO) is commonly thought to be the major cause. However, hydrogen cyanide (HCN) is also formed. Still, the exact contribution of HCN to fire-related fatalities is unknown. The aim of the study was to investigate the impact of HCN in relation to CO as a cause of death in fire victims. Data on carboxyhemoglobin (COHb) and blood cyanide from deceased fire victims in the period 1992–2009 were collected from two Swedish nationwide forensic databases (ToxBase and RättsBase). The databases contain data on COHb and/or cyanide from 2303 fire victims, whereof 816 on both COHb and cyanide. Nonparametric statistical tests were used. Seventeen percent of the victims had lethal or life-threatening blood cyanide levels (>1 µg/g) and 32% had lethal COHb levels (>50% COHb). Over 31% had cyanide levels above 0.5 µg/g, an indication of significant HCN exposure. The percentages may be underestimates, as cyanide is quickly eliminated in blood also after death. Our results support the notion that HCN contributes more to the cause of death among fire victims than previously thought.

A mass cyanide poisoning from pickling bamboo shoots

Context. Bamboo shoots contain cyanogenic glycosides named taxiphyllin. Cyanide poisoning from cyanogenic glycosides commonly occurs following ingestion. However, toxicity caused by inhalation of hydrogen cyanide gas (HCN) produced from pickled shoots has never been reported. Objective. To describe cyanide poisoning in eight victims who were exposed to HCN produced in a well containing pickling bamboo shoots. Materials and methods. Due to a series of botched rescue attempts, a total of eight patients entered into a 27 m3 well containing pickled bamboo shoots and immediately lost consciousness. After rescue, two patients developed cardiac arrest, metabolic acidosis and died. Four other patients suffered metabolic acidosis, but recovered after supportive care. The remaining two regained consciousness and recovered soon after the event. Ambient air study and cyanide content of bamboo shoots helped confirm the diagnosis. Results. All patients had high anion gap metabolic acidosis with normal oxygenation. Blood cyanide levels ranged from 2.66 to 3.30 mcg/ml (taken after about 18 h of incident). Ambient air study (21 h after incident) revealed oxygen 20.9%, and sulfur dioxide 19.4 ppm. The instrument was unfortunately not equipped to detect HCN. A simulation study revealed HCN and sulfur dioxide in the ambient air at 10 ppm and 7.5 ppm, respectively. Cyanide content in the bamboo shoots ranged from 39 to 434 mg/kg in the wet shoots. Discussion. This series of patients developed sudden onset of alteration of consciousness and metabolic acidosis upon exposure, and cyanide was confirmed in all victims. The simulation study confirmed the presence of HCN in the ambient air of the well containing bamboo shoots. Conclusion. We have reported mass acute cyanide poisoning with two fatalities. The source of HCN was unusual as it was produced from pickling bamboo shoot.

Rapid point of care analyzer for the measurement of cyanide in blood.

A simple, sensitive optical analyzer for the rapid determination of cyanide in blood in point of care applications is described. HCN is liberated by the addition of 20% H(3)PO(4) and is absorbed by a paper filter impregnated with borate-buffered (pH 9.0) hydroxoaquocobinamide (hereinafter called cobinamide). Cobinamide on the filter changes color from orange (λ(max) = 510 nm) to violet (λ(max) = 583 nm) upon reaction with cyanide. This color change is monitored in the transmission mode by a light emitting diode (LED) with a 583 nm emission maximum and a photodiode detector. The observed rate of color change increases 10 times when the cobinamide solution for filter impregnation is prepared in borate-buffer rather than in water. The use of a second LED emitting at 653 nm and alternate pulsing of the LEDs improves the limit of detection by 4 times to ~0.5 μM for a 1 mL blood sample. Blood cyanide levels of imminent concern (≥10 μM) can be accurately measured in ~2 min. The response is proportional to the mass of cyanide in the sample: smaller sample volumes can be successfully used with proportionate change in the concentration LODs. Bubbling air through the blood-acid mixture was found effective for mixing of the acid with the sample and the liberation of HCN. A small amount of ethanol added to the top of the blood was found to be the most effective means to prevent frothing during aeration. The relative standard deviation (RSD) for repetitive determination of blood samples containing 9 μM CN was 1.09% (n = 5). The technique was compared blind with a standard microdiffusion-spectrophotometric method used for the determination of cyanide in rabbit blood. The results showed good correlation (slope 1.05, r(2) 0.9257); independent calibration standards were used.

Intramuscular Cobinamide Sulfite in a Rabbit Model of Sublethal Cyanide Toxicity

Exposure to cyanide in fires and industrial exposures and intentional cyanide poisoning by terrorists leading to mass casualties is an ongoing threat. Current treatments for cyanide poisoning must be administered intravenously, and no rapid treatment methods are available for mass casualty cyanide exposures. Cobinamide is a cobalamin (vitamin B(12)) analog with an extraordinarily high affinity for cyanide that is more water-soluble than cobalamin. We investigate the use of intramuscular cobinamide sulfite to reverse cyanide toxicity-induced physiologic changes in a sublethal cyanide exposure animal model and determine the ability of an intramuscular cobinamide sulfite injection to rapidly reverse the physiologic effects of cyanide toxicity. New Zealand white rabbits were given 10 mg sodium cyanide intravenously over 60 minutes. Quantitative diffuse optical spectroscopy and continuous-wave near-infrared spectroscopy monitoring of tissue oxyhemoglobin and deoxyhemoglobin concentrations were performed concurrently with blood cyanide level measurements and cobinamide levels. Immediately after completion of the cyanide infusion, the rabbits were injected intramuscularly with cobinamide sulfite (n=6) or inactive vehicle (controls, n=5). Intramuscular administration led to rapid mobilization of cobinamide and was extremely effective at reversing the physiologic effects of cyanide on oxyhemoglobin and within deoxyhemoglobin extraction. Recovery time to 63% of their baseline values in the central nervous system occurred within a mean of 1,032 minutes in the control group and 9 minutes in the cobinamide group, with a difference of 1,023 minutes (95% confidence interval 116 to 1,874 minutes). In muscle tissue, recovery times were 76 and 24 minutes, with a difference of 52 minutes (95% confidence interval 7 to 98 minutes). RBC cyanide levels returned toward normal significantly faster in cobinamide sulfite-treated animals than in control animals. Intramuscular cobinamide sulfite rapidly and effectively reverses the physiologic effects of cyanide poisoning, suggesting that a compact cyanide antidote kit can be developed for mass casualty cyanide exposures.

W1630 Oral Microbiota in Inflammatory Bowel Disease and Recurrent Aphthous Stomatitis

G A A b st ra ct s Our study suggest that impaired butyrate oxidation is closely linked to the sulphide detoxification capacity of the mucosa in ulcerative colitis. The sulphide detoxification mechanism could explain the well-documented observation that cigarette smoking is beneficial in UC. Smoking increases blood cyanide levels and the colon has been shown to extract cyanide from blood. Hence, this cyanide could enhance the removal of thiosulphate from the colonic mucosa and thus facilitate the metabolism of sulphide to thiosulphate.