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Cyanide is a lethal poison that induces immediate fatality. Infrequently employed as a homicidal poison, it is not an ideal choice for homicide as it causes a 'dramatic' death causing suspicion among others. Cyanide is a rapidly metabolized poison that also rapidly disintegrates after death, posing challenges for chemical analysis, particularly when dealing with decomposed bodies. Detection of cyanide from a decomposed body is infrequent. A suspected case of intentional poisoning resulting in death was interred without conducting a postmortem examination. The exhumation process revealed the presence of hydrogen cyanide in the postmortem fluids collected from the body cavities three years after interment.
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PURPOSE: Forensic verification of cyanide (CN) poisoning by direct CN analysis in postmortem blood is challenging due to instability of CN in biological samples. CN metabolites, thiocyanate (SCN-) and 2-aminothiazoline-4-carboxylic acid (ATCA), have been proposed as more stable biomarkers, yet it is unclear if either is appropriate for this purpose. In this study, we evaluated the behavior of CN biomarkers in postmortem swine and postmortem blood to determine which serves as the best biomarker of CN exposure. METHODS: CN, SCN-, and ATCA were measured in postmortem swine (N = 8) stored at 4 °C and postmortem blood stored at 25 °C (room temperature, RT) and 37 °C (typical human body temperature, HBT). RESULTS: Following CN poisoning, the concentration of each CN biomarker increased well above the baseline. In postmortem swine, CN concentrations declined rapidly (t1/2 = 34.3 h) versus SCN- (t1/2 = 359 h, 15 days) and ATCA (t1/2 = 544 h, 23 days). CN instability in postmortem blood increased at RT (t1/2 = 10.7 h) and HBT (t1/2 = 6.6 h). SCN- and ATCA were more stable than CN at all storage conditions. In postmortem swine, the t1/2s of SCN- and ATCA were 15 and 23 days, respectively. While both the t1/2s of SCN- and ATCA were relatively lengthy, endogenous levels of SCN- were much more variable than ATCA. CONCLUSION: While there are still questions to be answered, ATCA was the most adept forensic marker of CN poisoning (i.e., ATCA produced the longest half-life, the largest increase above baseline levels, and most stable background concentrations).
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Biomarcadores , Cianuros , Animales , Cianuros/envenenamiento , Cianuros/sangre , Biomarcadores/sangre , Porcinos , Tiocianatos/envenenamiento , Tiocianatos/sangre , Tiocianatos/metabolismo , Toxicología Forense/métodos , Modelos Animales , Temperatura , Manejo de Especímenes/métodos , TiazolesRESUMEN
OBJECTIVE: Vitamin B17 tablets are sold (online) as an alternative cancer therapy medication. Its use however is not benign, given that it is metabolised into hydrogen cyanide. We aimed to measure the number of calls received by the New South Wales Poisons Information Centre (NSW PIC) regarding Amygdalin exposures. METHODS: A retrospective review of all amygdalin/cyanogenic glycoside product ingestion exposure calls to NSW PIC between 2015 and 2022. RESULTS: There were 120 unique exposure calls. Eighty-two (68%) were regarding minor exposures, with the remaining 38 (32%) of calls involving patients who had either a signifcant history or symptoms to prompt referral to hospital or were already seeking advice from a treating hospital clinican. CONCLUSION: There is a significant burden of concern generated from the misuse of cyanogenic glycoside products for cancer prevention and treatment, which can result in hospital admission carrying significant health risk and expenditure.
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Amigdalina , Neoplasias , Humanos , Estudios Retrospectivos , Nueva Gales del Sur/epidemiología , Masculino , Amigdalina/uso terapéutico , Amigdalina/farmacología , Femenino , Adulto , Persona de Mediana Edad , Centros de Control de Intoxicaciones/estadística & datos numéricos , Anciano , Adolescente , Niño , Glicósidos/uso terapéutico , Glicósidos/farmacologíaRESUMEN
Sorghum plants naturally produce dhurrin, a cyanogenic glycoside that may be hydrolysed to cyanide, resulting in often-lethal toxicoses. Ruminants are particularly sensitive to cyanogenic glycosides due to the active role of rumen microbiota in dhurrin hydrolysis. This work provides an overview of a poisoning outbreak that occurred in 5 farms in Northwest Italy in August 2022; a total of 66 cows died, and many others developed acute toxicosis after being fed on either cultivated (Sorghum bicolor) or wild Sorghum (Sorghum halepense). Clinical signs were recorded, and all cows received antidotal/supportive therapy. Dead animals were subjected to necropsy, and dhurrin content was determined in Sorghum specimens using an LC-MS/MS method. Rapid onset, severe respiratory distress, recumbency and convulsions were the main clinical features; bright red blood, a bitter almond smell and lung emphysema were consistently observed on necropsy. The combined i.v. and oral administration of sodium thiosulphate resulted in a rapid improvement of clinical signs. Dhurrin concentrations corresponding to cyanide levels higher than the tolerated threshold of 200 mg/kg were detected in sorghum specimens from 4 out of 5 involved farms; thereafter, such levels declined, reaching tolerable concentrations in September-October. Feeding cattle with wild or cultivated Sorghum as green fodder is a common practice in Northern Italy, especially in summer. However, care should be taken in case of adverse climatic conditions, such as severe drought and tropical temperatures (characterising summer 2022), which are reported to increase dhurrin synthesis and storage.
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A 45-year-old man attended to a warehouse fire involving burning plastic, without wearing full protective equipment. He subsequently presented to hospital with shortness of breath and his trachea was intubated for airway protection due to initial concerns of inhalational injury. However, a post-intubation bronchoscopy was normal. The patient's serum lactate level was normal on admission but was increased when measured 14 h after the initial event and accompanied by a metabolic acidosis. Transdermal cyanide poisoning was suspected given this delayed biochemical presentation and the absence of another apparent cause. A handheld chemical detector detected a high level of toxins on the patient's skin. Clinical improvement was not observed after the first dose of intravenous hydroxocobalamin, which was administered before full body decontamination. After decontamination and the administration of a second dose of hydroxocobalamin, the patient's acid-base status rapidly improved and serum lactate level returned to normal. Clinicians should have a high index of suspicion for transdermal cyanide poisoning in patients presenting after exposure to a fire.
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3-mercaptopyruvate sulfurtransferase (3-MST) plays the important role of producing hydrogen sulfide. Conserved from bacteria to Mammalia, this enzyme is localized in mitochondria as well as the cytoplasm. 3-MST mediates the reaction of 3-mercaptopyruvate with dihydrolipoic acid and thioredoxin to produce hydrogen sulfide. Hydrogen sulfide is also produced through cystathionine beta-synthase and cystathionine gamma-lyase, along with 3-MST, and is known to alleviate a variety of illnesses such as cancer, heart disease, and neurological conditions. The importance of cystathionine beta-synthase and cystathionine gamma-lyase in hydrogen sulfide biogenesis is well-described, but documentation of the 3-MST pathway is limited. This account compiles the current state of knowledge about the role of 3-MST in physiology and pathology. Attempts at targeting the 3-MST pathway for therapeutic benefit are discussed, highlighting the potential of 3-MST as a therapeutic target.
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Recently, 2-aminothiazoline-4-carboxylic acid (ATCA), a cyanide (CN) metabolite, has been proposed as a stable diagnostic marker of CN poisoning. In this study, liquid chromatography coupled with electrospray ionization - tandem mass spectrometry was used to quantify ATCA concentrations in human postmortem blood samples, and differences in ATCA concentrations according to age and sex were determined. Both age and sex had significant effects on blood ATCA concentrations. Although ATCA concentrations exhibited an inverted U shape with increasing age in men, in women ATCA concentrations plateaued at around 40-59 years of age. There were significant differences between the sexes in ATCA concentrations for the 20-39 and 40-59 year age groups (P < 0.05 and P < 0.01, respectively). Correlations between ATCA concentrations and carboxyhemoglobin (CO-Hb) saturation were also examined in fire victims. ATCA concentrations increased significantly with increasing CO-Hb saturation (r = 0.382, P < 0.01). In addition, ATCA concentrations were also correlated to CN concentrations (r = 0.309, P < 0.05). The results of our study may provide novel information about the contribution of CN poisoning to the cause of death at fire scenes.
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Carboxihemoglobina , Cianuros , Incendios , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carboxihemoglobina/análisis , Ácidos Carboxílicos , Cianuros/envenenamiento , Caracteres Sexuales , Adulto Joven , AutopsiaRESUMEN
Los casos de intoxicación por ingesta de cianuro en niños son raros. La almendra amarga contiene amigdalina y se descompone tras su ingesta, produciendo ácido cianhídrico que bloquea el uso celular del oxígeno, lo que ocasiona afectación de órganos diana. Presentamos un caso de sospecha de intoxicación por cianuro en un niño de 3 años tras ingesta de almendras amargas. El diagnóstico de sospecha se estableció con base en la clínica gastrointestinal y neurológica y en el hallazgo gasométrico de acidosis metabólica con hiperlactacidemia y anión GAP aumentado, lo cual es muy específico de esta entidad. No se pudieron determinar los niveles de cianuro en ningún laboratorio habitual de España, tampoco en el Instituto Toxicológico Nacional y Ciencias Forenses sin disponer de orden judicial. Ante la clínica inespecífica y las dificultades para determinar la concentración de cianuro en sangre, debe ofrecerse tratamiento precoz y antídoto específico ante la sospecha de intoxicación por cianuro (AU)
Cyanide poisoning in children is rare. Bitter almonds contain amygdalin, and hydrolysis of this compound following ingestion yields hydrocyanic acid, which inhibits cellular oxygen use and therefore causes target organ damage. We present a case of suspected cyanide poisoning in a child aged 3 years after the ingestion of bitter almonds. The diagnosis was based on the gastrointestinal and neurological symptoms and the detection of metabolic acidosis with hyperlacticaemia and a high anion gap, which are highly specific for this type of poisoning. Blood cyanide levels could not be measured in any clinical laboratory in Spain, and it was also not possible to do it in the National Institute of Toxicology and Forensic Sciences without a court order. Given the non-specific symptoms and the difficulty of measuring the concentration of cyanide in blood, treatment should be initiated early with administration of specific antidote if cyanide poisoning is suspected. (AU)
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Humanos , Masculino , Preescolar , Enfermedades Transmitidas por los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/diagnóstico , Prunus dulcis/efectos adversos , Prunus dulcis/química , Cianuros/toxicidadRESUMEN
Liposome-encapsulated methemoglobin (metHb@Lipo) has been developed as a novel antidote for cyanide poisoning. Antidotes for lethal acute poisoning should be capable of being easily stored as ready-to-use formulations without temperature restrictions. Here, we investigated the pharmaceutical stability of the metHb@Lipo suspension after one-year storage as a ready-to-use formulation at 4 °C, room temperature (23-28 °C) and 37 °C. The liposomal integrity of metHb@Lipo was observed after one year of storage at all storage temperatures with no physicochemical change or methemoglobin leakage outside the liposome. Furthermore, the encapsulated methemoglobin remained intact without aggregation, fragmentation, denaturation, or dissociation of heme. Fresh and stored metHb@Lipo were equivalent in their binding affinity against cyanide. Moreover, all one-year stored metHb@Lipo suspensions improved the mortality rates of lethal cyanide poisoning mice comparable to fresh metHb@Lipo suspension. Additionally, all stored metHb@Lipo suspensions preserved high biocompatibility, including blood compatibility and the lack of organ toxicity. In conclusion, the metHb@Lipo suspension was a pharmaceutically stable antidote for cyanide poisoning for at least one year without any temperature restrictions.
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Antídotos , Metahemoglobina , Animales , Cianuros , Liposomas , RatonesRESUMEN
This comparative cross-sectional study aimed to better understand the respective contributions of protein malnutrition and cassava-derived cyanide poisoning in the development of konzo. We compared data on nutritional status and cyanide exposure of school-age adolescent konzo-diseased patients to those of non-konzo subjects of similar age from three areas in the Eastern Democratic Republic of the Congo. Our results show that konzo patients had a high prevalence of both wasting (54.5%) and stunting (72.7%), as well as of cyanide poisoning (81.8%). Controls from Burhinyi and those from Idjwi showed a similar profile with a low prevalence of wasting (3.3% and 6.5%, respectively) and intermediate prevalence of stunting (26.7% and 23.9%, respectively). They both had a high prevalence of cyanide poisoning (50.0% and 63.0%, respectively), similar to konzo-patients. On the other hand, controls from Bukavu showed the lowest prevalence of both risk factors, namely chronic malnutrition (12.1%) and cyanide poisoning (27.6%). In conclusion, cassava-derived cyanide poisoning does not necessarily coexist with konzo outbreaks. The only factor differentiating konzo patients from healthy individuals exposed to cyanide poisoning appeared to be their worse nutritional status. This further suggests that, besides the known role of cyanide poisoning in the pathogenesis of konzo, malnutrition may be a key factor for the disease occurrence.
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Estado Nutricional , Paraparesia Espástica/complicaciones , Paraparesia Espástica/epidemiología , Adolescente , Estudios Transversales , Cianuros , República Democrática del Congo/epidemiología , Brotes de Enfermedades , Femenino , Humanos , Masculino , Desnutrición , Manihot , Prevalencia , Factores de Riesgo , VerdurasRESUMEN
Cyanide induces acute lethal poisoning resulting from inhibition of cytochrome c oxidase located in the complex IV (Complex IV) of mitochondria. However, current therapies for cyanide poisoning using hydroxocobalamin and nitrous acid compounds remain a clinical issue. Here, we show that liposome-encapsulated methemoglobin (metHb@Lipo), nanosized biomimetic red blood cells, replicate the antidotal mechanism of nitrous acid compounds against cyanide poisoning, achieving superior efficacy and fast action with no adverse effects. The structure of metHb@Lipo, which consists of concentrated methemoglobin in its aqueous core and a lipid membrane resembling the red blood cell membrane, provides favorable characteristics as a cyanide antidote, such as binding properties and membrane permeability. Upon cyanide exposure, metHb@Lipo maintained the mitochondrial function in PC12 cells, resulting in a cell viability comparable to treatment with nitrous acid compounds. In a mouse model of cyanide poisoning, metHb@Lipo treatment dramatically improved mortality with a rapid recovery from the symptoms of cyanide poisoning compared to treatment with nitrous acid compounds. Furthermore, metHb@Lipo also possesses satisfactory pharmacokinetic properties without long-term bioaccumulation and toxicity. Our findings showed a novel concept to develop drugs for cyanide poisoning and provide a promising possibility for biomimetic red blood cell preparations for pharmaceutical applications.
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Antídotos , Metahemoglobina , Animales , Antídotos/uso terapéutico , Cianuros , Eritrocitos , Liposomas , Ratones , RatasRESUMEN
OBJECTIVES: Hydroxocobalamin (OHCob) is an antidote for cyanide poisoning in patients rescued from house fires and is known to cause interference with certain laboratory tests. Consensus is lacking on the extent of this interference and on how to handle these samples. The objectives of this study were to characterize OHCob interference across a wide range of laboratory tests and to develop protocols for identifying and reporting these samples. DESIGNS & METHODS: Patient plasma samples (n = 5) were spiked with OHCob (1.5 mg/mL) and compared to controls without this drug. A series of analytes were measured using chemistry, urinalysis, coagulation, hematology, and blood gas instruments. Dose-response testing was performed on a subset of assays that showed interferences ≥10%. RESULTS: Of the 77 analytes evaluated, 27 (35%) showed interference from OHCob, with chemistry and coagulation analytes showing the greatest effects. Of those affected, 22 analytes had a positive interference, whereas 5 analytes had negative interference. Dose-response studies showed dose-dependent increases and/or decreases consistent with initial spiking studies. Although red in colour, plasma samples with OHCob did not trigger hemolysis index flags, necessitating a special sample identification and reporting protocol. CONCLUSION: OHCob had significant effects on several analytes across different instruments. These findings led to the development of special sample handling and reporting protocols to identify OHCob samples and ensure only accurate results are released. It is vital for emergency departments to document and notify their laboratories whenever blood samples from these patients are drawn.
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Antídotos/farmacocinética , Análisis Químico de la Sangre , Hidroxocobalamina/farmacocinética , Intoxicación , Cianuro de Potasio , Antídotos/administración & dosificación , Femenino , Humanos , Hidroxocobalamina/administración & dosificación , Masculino , Intoxicación/sangre , Intoxicación/tratamiento farmacológicoRESUMEN
The inefficiency of cyanide/HCN (CN) binding with heme proteins (under physiological regimes) is demonstrated with an assessment of thermodynamics, kinetics, and inhibition constants. The acute onset of toxicity and CN's mg/Kg LD50 (µM lethal concentration) suggests that the classical hemeFe binding-based inhibition rationale is untenable to account for the toxicity of CN. In vitro mechanistic probing of CN-mediated inhibition of hemeFe reductionist systems was explored as a murburn model for mitochondrial oxidative phosphorylation (mOxPhos). The effect of CN in haloperoxidase catalyzed chlorine moiety transfer to small organics was considered as an analogous probe for phosphate group transfer in mOxPhos. Similarly, inclusion of CN in peroxidase-catalase mediated one-electron oxidation of small organics was used to explore electron transfer outcomes in mOxPhos, leading to water formation. The free energy correlations from a Hammett study and IC50/Hill slopes analyses and comparison with ligands ( CO/ H 2 S/ N 3 - ) $\left( {\text{CO}}/{{{{\text{H}}_{2}}\text{S}}/{\text{N}_{3}^{\text{-}}}\;}\; \right)$ provide insights into the involvement of diffusible radicals and proton-equilibriums, explaining analogous outcomes in mOxPhos chemistry. Further, we demonstrate that superoxide (diffusible reactive oxygen species, DROS) enables in vitro ATP synthesis from ADP+phosphate, and show that this reaction is inhibited by CN. Therefore, practically instantaneous CN ion-radical interactions with DROS in matrix catalytically disrupt mOxPhos, explaining the acute lethal effect of CN.
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Cianuros/toxicidad , Hemo/química , Hemoproteínas/antagonistas & inhibidores , Hemoglobinas/antagonistas & inhibidores , Mitocondrias/efectos de los fármacos , Adenosina Trifosfato/biosíntesis , Adenosina Trifosfato/química , Adenosina Trifosfato/metabolismo , Sitios de Unión , Catalasa/metabolismo , Catálisis , Respiración de la Célula/efectos de los fármacos , Respiración de la Célula/fisiología , Cloruro Peroxidasa/química , Cianuros/química , Complejo IV de Transporte de Electrones/química , Complejo IV de Transporte de Electrones/metabolismo , Hemo/antagonistas & inhibidores , Hemo/metabolismo , Hemoproteínas/química , Hemoproteínas/metabolismo , Hemoglobinas/química , Peroxidasa de Rábano Silvestre/metabolismo , Hidróxidos/química , Cinética , Ligandos , Mitocondrias/química , Mitocondrias/enzimología , Mitocondrias/metabolismo , Oxidación-Reducción , Especies Reactivas de Oxígeno/metabolismo , Estirenos/química , Estirenos/farmacología , Superóxidos/química , TermodinámicaRESUMEN
Background: Cyanide is a metabolic poison used in multiple industries and is a high threat chemical agent. Current antidotes require intravenous administration, limiting their usefulness in a mass casualty scenario. Sodium tetrathionate reacts directly with cyanide yielding thiosulfate and the non-toxic compound thiocyanate. Thiosulfate, in turn, neutralizes a second molecule of cyanide, thus, per mole, sodium tetrathionate neutralizes two moles of cyanide. Historical studies examined its efficacy as a cyanide antidote, but it has not been evaluated in a clinically relevant, large animal model, nor has it previously been administered by intramuscular injection.Objective: The objective of this study is to evaluate the efficacy of intramuscular sodium tetrathionate on survival and clinical outcomes in a large, swine model of severe cyanide toxicity.Methods: Anesthetized swine were instrumented for continuous monitoring of hemodynamics, then acclimated and breathing spontaneously prior to potassium cyanide infusion (0.17 mg/kg/min). At 6-min post-apnea (no breaths for 20 s), the cyanide infusion was terminated, and animals were treated with sodium tetrathionate (â¼18 mg/kg) or normal saline control. Clinical parameters and laboratory values were evaluated at various time points until death or termination of the experiment (90 min post-treatment).Results: Laboratory values, vital signs, and time to apnea were similar in both groups at baseline and treatment. Survival in the sodium tetrathionate treated group was 100% and 17% in controls (p = 0.0043). All animals treated with sodium tetrathionate returned to breathing at a mean time of 10.85 min after antidote, and all but one control remained apneic through end of the experiment. Animals treated with tetrathionate showed improvement in blood lactate (p ≤ 0.002) starting at 30 min post-treatment. The average time to death in the control group is 63.3 ± 23.2 min. No systemic or localized adverse effects of intramuscular administration of sodium tetrathionate were observed.Conclusion: Sodium tetrathionate significantly improves survival and clinical outcomes in a large, swine model of acute cyanide poisoning.
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Antídotos/uso terapéutico , Cianuros/toxicidad , Ácido Tetratiónico/uso terapéutico , Animales , Antídotos/administración & dosificación , Cianuros/antagonistas & inhibidores , Modelos Animales de Enfermedad , Femenino , Inyecciones Intramusculares , Porcinos , Ácido Tetratiónico/administración & dosificaciónRESUMEN
Hemodialysis machines are equipped with a blood leak detector/alarm to prevent loss of blood following rupture of semipermeable membrane; the blood leak alarms could also be triggered by sensor malfunction or presence of air bubbles in the system. Hydroxocobalamin is a Food and Drug Administration-approved rapid-acting antidote to cyanide poisoning that converts cyanide to nontoxic cyanocobalamin. Side effects are reddish discoloration of skin and body fluids, urticarial rash, and rarely anaphylaxis. In this article, a case of false blood leak alarm following treatment of cyanide poisoning with hydroxocobalamin is reported, wherein the blood leak detector in dialysis machines prevented the patient from undergoing hemodialysis by repeatedly activating blood leak alarms. Continuous renal replacement therapy was used to overcome this problem. As the use of hydroxocobalamin increases, health care professionals should be educated about its potential to interfere with hemodialysis.
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Antídotos/uso terapéutico , Alarmas Clínicas , Cianuros/envenenamiento , Hidroxocobalamina/uso terapéutico , Diálisis Renal/instrumentación , Anciano , Color , Reacciones Falso Positivas , Humanos , Masculino , Intoxicación/terapiaRESUMEN
In recent years, Cobinamide (Cbi) has shown promise as a therapeutic for cyanide poisoning. There are several forms of Cbi based on the identity of the ligands bound to the cobalt in Cbi and these different forms of Cbi have divergent behavior (e.g., the aquo and hydroxo forms of Cbi readily bind to proteins, limiting their distribution significantly, whereas [Cbi(CN)2] does not). While current analysis techniques only measure total Cbi, methods to elucidate the behavior of 'available' Cbi versus cyanide-complexed Cbi would be valuable for biomedical and pharmacokinetic studies. Therefore, a method was developed for the analysis of cyanide-complexed Cbi in plasma via liquid chromatography tandem mass spectrometry (LC-MS-MS). Plasma samples were prepared by denaturing proteins with 10% ammonium hydroxide in acetonitrile. The resulting mixture was centrifuged, and the supernatant was removed, dried, and reconstituted. Cyanide-complexed Cbi was then analyzed via LC-MS-MS. The limit of detection was 0.2⯵M, and the linear dynamic range was between 1 and 200⯵M. The accuracy was 100⯱â¯17% and the precision, measured by relative standard deviation (%RSD), was ≤18.5%. Carryover, a severe problem when analyzing Cbi via liquid chromatography was eliminated using a polymeric-based stationary phase (PLRP-S) and a controlled washing protocol. The method allowed evaluation of the cyanide-bound and 'available' Cbi from treated animals and, when paired with a method for total Cbi analysis, allows for estimation of Cbi utilization when treating cyanide poisoning.
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Cromatografía Líquida de Alta Presión/métodos , Cobamidas/sangre , Espectrometría de Masas en Tándem/métodos , Animales , Cianuros/sangre , Límite de Detección , Plasma/química , Conejos , PorcinosRESUMEN
Cyanide toxicity is a fatal condition if not detected and treated in stipulated time. Lack of rapid detection modalities, and nonspecific nature of clinical presentation make the diagnosis more challenging. Cherry red colour of blood might be the only clue sometimes. We present a case of sudden onset altered sensorium which was detected as cyanide poisoning and treated successfully with antidots on the basis of central venous blood colour and corroborative presentation. HOW TO CITE THIS ARTICLE: Panigrahi N, Haranath P et al. Cyanide Toxicity!! Colour of Blood Says It All. Indian J Crit Care Med 2019;23(3):155-156.
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Cyanide (CN) is one of the most toxic of all substances and can be found in various natural and anthropogenic sources. Sensitive and effective methods for the confirmation of CN exposure are crucial in medical, military, and forensic settings. Due to its high volatility and reactivity, direct detection of CN from postmortem samples could raise inconclusive interpretation issues that may hinder accurate determination of the cause of death. The detection of the alternative CN metabolites as markers to test CN exposure may offer a solution to reduce the potential for false-negative and false-positive results. 2-Aminothiazoline-4-carboxylic acid (ATCA) is a minor metabolite of CN and has been proposed to be a potential alternative forensic marker for the confirmation of CN exposure. According to the current state of knowledge, ATCA has not yet been associated with other metabolic pathways except for CN detoxification. Moreover, ATCA is stable under various conditions over time. This article reviews analytical methods developed for the analysis of ATCA as well as studies related to potential use of ATCA as a marker for the diagnosis of CN exposure. The need for research related to the use of ATCA as a reliable forensic marker for CN exposure in medicolegal death investigations is also discussed.
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Biomarcadores/análisis , Cianuros/toxicidad , Intoxicación/diagnóstico , Tiazoles/análisis , Animales , Cromatografía Liquida , Cianuros/farmacocinética , Cianuros/envenenamiento , Dieta , Incendios , Fluorometría , Alimentos , Toxicología Forense , Cromatografía de Gases y Espectrometría de Masas , Humanos , Exposición por Inhalación/análisis , Extracción Líquido-Líquido , Estructura Molecular , Extracción en Fase Sólida , Espectrofotometría , Tiazoles/químicaRESUMEN
BACKGROUND: Cyanide is a deadly compound used as a terrorist agent. Current FDA approved antidotes require intravenous administration, limiting their utility in a mass casualty scenario. Dimethyl trisulfide (DMTS), a sulfur-based molecule, binds cyanide converting it to the less toxic by-product thiocyanate. Studies evaluating efficacy in rodents have been performed, but a large, clinically relevant animal model has not been reported. OBJECTIVE: This study evaluates the efficacy of intramuscular DMTS on survival and clinical outcomes in a swine model of acute, severe cyanide toxicity. METHODS: Anesthetized swine were instrumented for continuous monitoring of hemodynamics. Prior to potassium cyanide infusion animals were acclimated and breathing spontaneously. At 5-minutes post-apnea animals were treated with DMTS or saline. Vital signs, hemodynamics, and laboratory values were evaluated at various time points. RESULTS: Baseline values and time to apnea were similar in both groups. Survival in the DMTS treated group was 83.3% and 0% in saline controls (p = .005). The DMTS group returned to breathing at a mean time of 19.3 ± 10 min after antidote, control animals did not return to breathing (CI difference 8.8, 29.8). At the end of the experiment or time of death, mean lactate was 9.41 mmol/L vs. 4.35 mmol/L (CI difference -10.94,0.82) in the saline and DMTS groups, respectively and pH was 7.20 vs. 7.37 (CI difference -0.04, 0.38). No adverse effects were observed at the injection site. CONCLUSION: Intramuscular administration of DMTS improves survival and clinical outcomes in our large animal swine model of acute cyanide toxicity.