The Combination of Zhuli Decoction and N-butylphthalide Inhibits Cell Apoptosis Induced by CO Poisoning through the PI3K/AKT/GSK-3ß Signaling Pathway.

Carbon monoxide poisoning (COP) represents a significant global health burden, characterized by its morbidity and high mortality rates. The pathogenesis of COP-induced brain injury is complex, and effective treatment modalities are currently lacking. In this study, we employed network pharmacology to identify therapeutic targets and associated signaling pathways of Zhuli Decoction (ZLD) for COP. Subsequently, we conducted both in vitro and in vivo experiments to validate the therapeutic efficacy of ZLD in combination with N-butylphthalide (NBP) for acute COP-induced injury. Our network pharmacology analysis revealed that the primary components of ZLD exerted therapeutic effects through the modulation of multiple targets and pathways. The in vitro and in vivo experiments demonstrated that the combination of NBP and ZLD effectively inhibited apoptosis and up-regulated the activities of P-PI3K (Tyr458), P-AKT (Ser473), P-GSK-3ß (Ser9), and Bcl-2, thus leading to the protection of neuronal cells and improvement in cognitive function in rats following COP, which was better than the effects observed with NBP or ZLD alone. The rescue experiment further showed that LY294002, a PI3K inhibitor, significantly attenuated the therapeutic efficacy of NBP + ZLD. The neuroprotection effects of NBP and ZLD against COP-induced brain injury are closely linked to the activation of the PI3K/AKT/GSK-3ß signaling pathway.

Secuelas neurológicas tardías en la intoxicación por monóxido de carbono. Reporte de un caso pediátrico

Introducción: la intoxicación por monóxido de carbono (CO) es un problema grave de salud. La aparición de secuelas neurológicas tardías incluye trastornos cognitivos, mentales, síntomas piramidales o extrapiramidales. Caso clínico: paciente de 12 años, sexo femenino, luego de 15 días de una intoxicación aguda grave por CO, presenta movimientos coreoatetoideos de miembros superiores, distonías de cuello, discinesias de cara, bradipsiquia y dificultades en la memoria. Resonancia magnética: lesiones isquémicas en globo pálido bilateral, sustancia blanca de hipocampo y cerebelo. Discusión: es fundamental el seguimiento posterior al alta para reconocer las secuelas neurológicas tardías, incluyendo la realización de pruebas neuropsicológicas estandarizadas.

Introduction: Carbon monoxide poisoning is a severe health problem. The appearance of delayed neurological sequelae includes cognitive and mental disorders and pyramidal or extrapyramidal symptoms. Case presentation: A 12-year-old female patient, after 15 days of severe acute CO poisoning, presents choreoathetoid movements of the upper limbs, neck dystonias, face dyskinesias, bradypsychia, and memory difficulties. Magnetic resonance imaging: ischemic lesions in bilateral globus pallidus, the white matter of hippocampus and cerebellum. Discussion: A follow-up visit after discharge is essential to recognize delayed neurological sequelae, including performing standardized neuropsychological tests.

Effect and molecular mechanism of Sulforaphane alleviates brain damage caused by acute carbon monoxide poisoning:Network pharmacology analysis, molecular docking, and experimental evidence.

Sulforaphane (SFN) has attracted much attention due to its ability on antioxidant, anti-inflammatory, and anti-apoptotic properties, while its functional targets and underlying mechanism of action on brain injury caused by acute carbon monoxide poisoning (ACOP) have not been fully elucidated. Herein, we used a systematic network pharmacology approach to explore the mechanism of SFN in the treatment of brain damage after ACOP. In this study, the results of network pharmacology demonstrated that there were a total of 81 effective target genes of SFN and 36 drug-disease targets, which were strongly in connection with autophagy-animal signaling pathway, drug metabolism, and transcription disorders in cancer. Upon the further biological function and KEGG signaling pathway enrichment analysis, a large number of them were involved in neuronal death, reactive oxygen metabolic processes and immune functions. Moreover, based on the results of bioinformatics prediction associated with multiple potential targets and pathways, the AMP-activated protein kinase (AMPK) signaling pathway was selected to elucidate the molecular mechanism of SFN in the treatment of brain injury caused by ACOP. The following molecular docking analysis also confirmed that SFN can bind to AMPKα well through chemical bonds. In addition, an animal model of ACOP was established by exposure to carbon monoxide in a hyperbaric oxygen chamber to verify the predicted results of network pharmacology. We found that the mitochondrial ultrastructure of neurons in rats with ACOP was seriously damaged, and apoptotic cells increased significantly. The histopathological changes were obviously alleviated, apoptosis of cortical neurons was inhibited, and the number of Nissl bodies was increased in the SFN group as compared with the ACOP group (p < .05). Besides, the administration of SFN could increase the expressions of phosphorylated P-AMPK and MFN2 proteins and decrease the levels of DRP1, Caspase3, and Casapase9 proteins in the brain tissue of ACOP rats. These findings suggest that network pharmacology is a useful tool for traditional Chinese medicine (TCM) research, SFN can effectively inhibit apoptosis, protect cortical neurons from the toxicity of carbon monoxide through activating the AMPK pathway and may become a potential therapeutic strategy for brain injury after ACOP.

Carbon monoxide poisoning cases in the emergency department are increasing in the last decade in Jerusalem.

BACKGROUND AND AIMS: The aim of our study was to describe the epidemiology of Carbon monoxide poisoning in the Emergency Department. METHODS: A retrospective descriptive analysis of patients with Carbon monoxide poisoning who were presented to the Emergency Department of Hadassah hospital in Jerusalem from 2007 to 2016. All patients that were included are confirmed cases [carboxyhemoglobin level > 5%]. Sources of exposure, seasonal variation, and demographic characteristics were analyzed. RESULTS: There were 244 patients (60% males) with 37 family clusters that accounted for 135 (55.3%) patients. One hundred seventy-three (70.9%) patients presented during the winter months. The main sources of exposure were: non-gas residential heating system, mainly charcoal grills and kerosene stoves (n = 100, 41%). Other sources were fires (n = 70, 28.7%), faulty gas heater (n = 34, 13.9%) and smoking (n = 15, 6.1%). The estimated annual incidence increased from an average of 20.8 cases a year between 2007-2011 to an average of 34 cases in 2011-2016. High-risk poisoning (levels > 25%) occurred in 28 patients (11.5%). Factors associated with severe poisoning were female gender and exposure in clusters compared with individual patients. CONCLUSION: Our current study has showed an increase of Carbon Monoxide poisoning in contrary to our study performed in the previous decade. Fortunately, we did find a lower rate of cases with severe poisoning. Beside the implementation of safer standards for residential heating systems, customized public education is advised in order to lower rates of poisoning in the future. A predicted heavy snow fall should be considered a trigger for a public health warning regarding the risk of CO poisoning.

Aspectos por considerar en autopsias por intoxicación aguda con monóxido de carbono, el asesino silente. A propósito de dos casos / Aspects to consider in autopsies for acute carbon monoxide poisoning, the silent killer. About two cases

El monóxido de carbono (CO) es un gas que se produce durante la combustión incompleta de diferentes materiales orgánicos. Una vez que se inhala, se absorbe hacia la sangre, ejerciendo su efecto a nivel sistémico. Se une fuertemente a la hemoglobina, y forma la carboxihemoglobina lo que provoca una disminución del transporte de oxígeno a los tejidos y dependiendo de su concentración puede ser mortal. Los hallazgos comúnmente encontrados en la autopsia son color rojo cereza en la piel y órganos, así como edema pulmonar, entre otros. El diagnóstico de intoxicación por CO se basa en la medición post mortem de carboxihemoglobina en sangre, por lo que se deben tomar muestras para cuantificar estos niveles. Con respecto al manejo en estos casos, se presenta dos casos correspondientes a la autopsia médica legal en las que se estableció como causa de muerte la intoxicación por monóxido de carbono.

Carbon monoxide (CO) is a gas that is produced during the incomplete combustion of different organic materials. Once inhaled, it is absorbed into the blood, exerting its effect at the systemic level. It strongly binds to hemoglobin, and forms carboxyhemoglobin, which causes a decrease in oxygen transport to the tissues and, depending on its concentration, can be fatal. The findings commonly found in the autopsy are cherry red color in the skin and organs, as well as pulmonary edema, among others. The diagnosis of CO poisoning is based on the postmortem measurement of carboxyhemoglobin in the blood, so samples must be taken to quantify these levels. Regarding the handling of these cases, two cases corresponding to the legal medical autopsy are presented in which carbon monoxide poisoning was established as the cause of death.

Evaluation of a Portable Blood Gas Analyzer for Prehospital Triage in Carbon Monoxide Poisoning: Instrument Validation Study.

BACKGROUND: Carbon monoxide (CO) poisoning is an important cause of morbidity and mortality worldwide. Symptoms are mostly aspecific, making it hard to identify, and its diagnosis is usually made through blood gas analysis. However, the bulkiness of gas analyzers prevents them from being used at the scene of the incident, thereby leading to the unnecessary transport and admission of many patients. While multiple-wavelength pulse oximeters have been developed to discriminate carboxyhemoglobin (COHb) from oxyhemoglobin, their reliability is debatable, particularly in the hostile prehospital environment. OBJECTIVE: The main objective of this pilot study was to assess whether the Avoximeter 4000, a transportable blood gas analyzer, could be considered for prehospital triage. METHODS: This was a monocentric, prospective, pilot evaluation study. Blood samples were analyzed sequentially with 2 devices: the Avoximeter 4000 (experimental), which performs direct measurements on blood samples of about 50 µL by analyzing light absorption at 5 different wavelengths; and the ABL827 FLEX (control), which measures COHb levels through an optical system composed of a 128-wavelength spectrophotometer. The blood samples belonged to 2 different cohorts: the first (clinical cohort) was obtained in an emergency department and consisted of 68 samples drawn from patients admitted for reasons other than CO poisoning. These samples were used to determine whether the Avoximeter 4000 could properly exclude the diagnosis. The second (forensic) cohort was derived from the regional forensic center, which provided 12 samples from documented CO poisoning. RESULTS: The mean COHb level in the clinical cohort was 1.7% (SD 1.8%; median 1.2%, IQR 0.7%-1.9%) with the ABL827 FLEX versus 3.5% (SD 2.3%; median 3.1%, IQR 2.2%-4.1%) with the Avoximeter 4000. Therefore, the Avoximeter 4000 overestimated COHb levels by a mean difference of 1.8% (95% CI 1.5%-2.1%). The consistency of COHb readings by the Avoximeter 4000 was excellent, with an intraclass correlation coefficient of 0.97 (95% CI 0.93-0.99) when the same blood sample was analyzed repeatedly. Using prespecified cutoffs (5% in nonsmokers and 10% in smokers), 3 patients (4%) had high COHb levels according to the Avoximeter 4000, while their values were within the normal range according to the ABL827 FLEX. Therefore, the specificity of the Avoximeter 4000 in this cohort was 95.6% (95% CI 87%-98.6%), and the overtriage rate would have been 4.4% (95% CI 1.4%-13%). Regarding the forensic samples, 10 of 12 (83%) samples were positive with both devices, while the 2 remaining samples were negative with both devices. CONCLUSIONS: The limited difference in COHb level measurements between the Avoximeter 4000 and the control device, which erred on the side of safety, and the relatively low overtriage rate warrant further exploration of this device as a prehospital triage tool.

The Clinical Association between Carbon Monoxide Poisoning and Myocardial Injury as Measured by Elevated Troponin I Levels.

Carbon monoxide (CO) poisoning accounts for over 50,000 estimated emergency room visits and approximately 1200 deaths per year in the US. Despite the high prevalence, there is a paucity of data looking at the association between laboratory biomarkers and clinical outcomes. Our study investigates the association between myocardial injury as assessed by increased troponin levels and its effect on in-hospital outcomes in CO poisoning. A total of 900 sequential charts of patients presenting with CO poisoning between 1 January 2012, and 31 August 2019, at our tertiary center with regional hyperbaric chamber and burn unit, were reviewed. Of the 900, a total of 488 patients had elevated carboxyhemoglobin levels. Of these 488 patients, 119 (24.4%) also had blood troponin levels measured. Patients were stratified based on the presence or absence of myocardial injury as evidenced by highly sensitive serum troponin I (TnI) level > 0.5 ng/mL to determine if a correlation exists relating to myocardial injury and risk of major adverse events. Mean age was 51.2 years, 58.8% were males, 35.3% were non-White, and 10.1% were intentional CO poisonings. Comorbidities included hypertension: 37%, diabetes: 21%, smoking: 21%, hyperlipidemia: 17.6%, coronary artery disease: 11.8%, asthma: 5.9%, heart failure: 5%, atrial fibrillation: 4.2%, and chronic obstructive pulmonary disease: 4.2%. Myocardial injury occurred in 22 patients (18.5%) and was associated with increased likelihood of requiring intensive care admission (54.5% vs. 20.6%, p = 0.002) and intubation (40.9% vs. 14.4%, p = 0.008). TnI elevation was associated with higher in-hospital mortality (p = 0.008, OR 21.3) compared to patients without TnI elevation. Older age was independently associated with increased in-hospital mortality (p = 0.03, OR 1.08). When controlling for age, in-hospital mortality remained statistically significant (p = 0.01, OR 21.37). No significant difference was found with respect to age, comorbidities, gender, race, ethnicity, or hospital length of stay in patients with and without myocardial injury. Myocardial injury induced by CO exposure occurs frequently and adversely affects clinical outcomes. Further research is needed to help guide physicians in the management of CO poisoning and associated myocardial injury to improve patient outcomes.

Neuro-protective effects of n-butylphthalide on carbon monoxide poisoning rats by modulating IL-2, AKT and BCL-2.

Acute carbon monoxide poisoning (CO-poisoning) causes neurotoxicity by inducing necrosis, apoptosis, lipid peroxidation, and oxidative stress. DL-3-n-butylphthalide (NBP) is a synthetic compound originally extracted from the seeds of Chinese celery and based on pure l-3-n-butylphthalide. In ischemia/reperfusion, it exerts neuroprotective effects through its anti-apoptotic, anti-necrotic and antioxidant properties, and activation of pro-survival pathways. Our study performed bioinformatic analysis to identify the differential expression genes. CO-poisoning patients' blood was collected to confirm the findings. Male rats were exposed to CO 3000 ppm for 40 min, and NBP (100 mg/kg/day) was continuously injected intraperitoneally immediately after poisoning and for the next 15 days. After NBP treatment, the rats were evaluated by Morris water maze test. At the end of experiments, blood and brain tissues of the rats were collected to evaluate the expression levels of IL-2, AKT and BCL-2. We found that IL-2 was elevated in CO-poisoning patients and animal models. Brain tissue damage in CO-poisoning rats was significantly alleviated after NBP treatment. Furthermore, NBP increased the expression of IL-2, AKT and BCL-2 in rat CO-poisoning model. NBP showed neuroprotective action by increasing IL-2, AKT, and BCL-2 expressions.

Extracorporeal membrane oxygenators with light-diffusing fibers for treatment of carbon monoxide poisoning: Experiments, mathematical modeling, and performance assessment with unit cells.

BACKGROUND AND OBJECTIVES: Approximately 50,000 emergency department visits per year due to carbon monoxide (CO) poisoning occur in the United States alone. Tissue hypoxia can occur at very low CO concentration exposures because CO binds with a 250-fold higher affinity than oxygen to hemoglobin. The most effective therapy is 100% hyperbaric oxygen (HBO) respiration. However, there are only a limited number of cases with ready accessibility to the specialized HBO chambers. In previous studies, we developed an extracorporeal veno-venous membrane oxygenator that facilitates exposure of blood to an external visible light source to photo-dissociate carboxyhemoglobin (COHb) and significantly increase CO removal from CO-poisoned blood (photo-extracorporeal veno-venous membrane oxygenator [p-ECMO]). One objective of this study was to describe in vitro experiments with different laser wavelength sources to compare CO elimination rates in a small unit-cell ECMO device integrated with a light-diffusing optical fiber. A second objective was to develop a mathematical model that predicts CO elimination rates in the unit-cell p-ECMO  device design upon which larger devices can be based. STUDY DESIGN/MATERIAL AND METHODS: Two small unit-cell p-ECMO devices consisted of a plastic capillary with a length and inside diameter of 10 cm and 1.15 mm, respectively. Either five (4-1 device) or seven (6-1 device) gas exchange tubes were placed in the plastic capillary and a light-diffusing fiber was inserted into one of the gas exchange tubes. Light from lasers emitting either 635 nm or 465 nm wavelengths was coupled into the light-diffusing fiber as oxygen flowed through the gas exchange membranes. To assess the ability of the device to remove CO from blood in vitro, the percent COHb reduction in a single pass through the device was assessed with and without light. The Navier Stokes equations, Carreau-Yesuda model, Boltzman equation for light distribution, and hemoglobin kinetic rate equations, including photo-dissociation, were combined in a mathematical model to predict COHb elimination in the experiments. RESULTS: For the unit-cell devices, the COHb removal rate increases with increased 635 nm laser power, increased blood time in the device, and greater gas exchange membrane surface-to-blood volume ratio. The 6-1 device COHb half-life versus that of the 4-1 device with 4 W at 635 nm light was 1.5 min versus 4.25 min, respectively. At 1 W laser power, 635 nm and 465 nm exhibited similar CO removal rates. The COHb half-life times of the 6-1 device were 1.25, 2.67, and 8.5 min at 635 nm (4 W), 465 nm (1 W), and 100% oxygen only, respectively. The mathematical model predicted the experimental results. An analysis of the in vivo COHb half-life of oxygen respiration therapy versus an adjunct therapy with a p-ECMO device and oxygen respiration shows a reduction from 90 min to as low as 10 min, depending on the device design. CONCLUSION: In this study, we experimentally studied and developed a mathematical model of a small unit-cell ECMO device integrated with a light-diffusing fiber illuminated with laser light. The unit-cell device forms the basis for a larger device and, in an adjunct therapy with oxygen respiration, has the potential to remove COHb at much higher rates than oxygen therapy alone. The mathematical model can be used to optimize the design in practical implementations to quickly and efficiently remove CO from CO-poisoned blood.

Optical, flow, and thermal analysis of a phototherapy extracorporeal membrane oxygenator for treating carbon monoxide poisoning.

BACKGROUND: Extracorporeal membrane oxygenators (ECMO) are currently utilized to mechanically ventilate blood when lung or lung and heart function are impaired, like in cases of acute respiratory distress syndrome (ARDS). ARDS can be caused by severe cases of carbon monoxide (CO) inhalation, which is the leading cause of poison-related deaths in the United States. ECMOs can be further optimized for severe CO inhalation using visible light to photo-dissociate CO from hemoglobin (Hb). In previous studies, we combined phototherapy with an ECMO to design a photo-ECMO device, which significantly increased CO elimination and improved survival in CO-poisoned animal models using light at 460, 523, and 620 nm wavelengths. Light at 620 nm was the most effective in removing CO. OBJECTIVE: The aim of this study is to analyze the light propagation at 460, 523, and 620 nm wavelengths and the 3D blood flow and heating distribution within the photo-ECMO device that increased CO elimination in CO-poisoned animal models. METHODS: Light propagation, blood flow dynamics, and heat diffusion were modeled using the Monte Carlo method and the laminar Navier-Stokes and heat diffusion equations, respectively. RESULTS: Light at 620 nm propagated through the device blood compartment (4 mm), while light at 460 and 523 nm only penetrated 48% to 50% (~2 mm). The blood flow velocity in the blood compartment varied with regions of high (5 mm/s) and low (1 mm/s) velocity, including stagnant flow. The blood temperatures at the device outlet for 460, 523, and 620 nm wavelengths were approximately 26.7°C, 27.4°C, and 20°C, respectively. However, the maximum temperatures within the blood treatment compartment rose to approximately 71°C, 77°C, and 21°C, respectively. CONCLUSIONS: As the extent of light propagation correlates with efficiency in photodissociation, the light at 620 nm is the optimal wavelength for removing CO from Hb while maintaining blood temperatures below thermal damage. Measuring the inlet and outlet blood temperatures is not enough to avoid unintentional thermal damage by light irradiation. Computational models can help eliminate risks of excessive heating and improve device development by analyzing design modifications that improve blood flow, like suppressing stagnant flow, further increasing the rate of CO elimination.

Intoxicación por monóxido de carbono: estudio observacional de pacientes que acudieron a Urgencias durante 2020 / Carbon monoxide poisoning: an observational study of patients admitted to Emergency Department during 2020

El objetivo fue describir las intoxicaciones monóxido de carbono. Se diseñó un corte transversal que incluyó una muestra consecutiva de mediciones de carboxihemoglobina (COHb), realizadas Enero y Diciembre 2020 en la Central de Emergencias del Hospital Italiano de Buenos Aires. Se utilizaron bases secundarias y revisión manual de historias clínicas para recolección de varia-bles de interés. Durante el período de estudio hubo 20 pacientes confirmados, con media de 50 años (DE 20), 55% sexo masculino, 20% tabaquistas, y una única embarazada. El 70% correspondieron al trimestre Junio-Julio-Agosto. La fuente de intoxicación más frecuente se debió a accidentes domésticos (calefón, estufa, brasero, hornalla, salamandra) que representaron el 50% de los casos, 30% por incendios, y el 20% restante explicado por tabaco o factor desconocido. Los estudios de laboratorio más solicitados fueron: 95% recuento de glóbulos blancos, 85% glucemia, 70% CPK, y 55% troponina. Los hallazgos relevantes fueron COHb con mediana de 7.15%, CPK con mediana de 89 U/mL, y troponina con mediana de 8.5 pg/mL. La totalidad se realizó electrocardiograma: 15% presentaron arritmia como hallazgo patológico, y ninguno isquemia. En cuanto la presentación clínica: 30% presentó cefalea, 15% síncope, 15% coma, 10% mareos y 10% convulsiones. Sólo 25% tuvieron tomografía y 15% resonancia de cerebro, sin hallazgos críticos. Sin embargo, 15% fueron derivados para trata-miento con cámara hiperbárica. La mayoría ocurrieron en invierno y explicados por accidentes domésticos. Será necesario un fortalecimiento del rol preventivo que apunte al control de la instalación y el buen funcionamiento de artefactos, como mantener los ambientes bien ventilados (AU)

The objective was to describe carbon monoxide poisoning. A cross sectional was designed, which included a consecutive sample of carboxyhemoglobin (COHb) measurements, carried from January to December 2020 at the Emergency Department of tHospital Italiano de Buenos Aires. Secondary databases and manual review of medical records were used to collect variables of interest. During the study period there were 20 confirmed patients, with a mean age of 50 (SD 20), mostly male (55%), 20% smokers, and only one pregnant woman, 70% corresponded to June-July-August. The most frequent source of poisoning was explained to domestic accidents (water heater, stove, brazier, stove, salamander) which represented 50% of cases, 30% due to fires, and the remaining 20% by tobacco or unknown factor. The most laboratory studies were: 95% white blood cell count, 85% glycemia, 70% CPK, and 55% troponin. Meanwhile, relevant findings were carboxyhemoglobin with a median of 7.15%, CPK with a median of 89 U/mL, and troponin with a median of 8.5 pg/mL. All underwent an electrocardiogram: 15% presented arrhythmia as a pathological finding, and none ischemia. Regarding the clinical presentation: 30% presented headache, 15% syncope, 15% coma, 10% dizziness and 10% seizures. Only 25% had brain tomography and 15% MRI, without pathological findings. However, 15% were referred for treatment with a hyperbaric chamber. Most of the cases occurred in winter and explained by domestic accidents. It will be necessary to strengthen the preventive role that aims to control the installation and the proper functioning of devices, such as keeping rooms well ventilated (AU)

Correlation Between Rats Hippocampal ATP Content and Delayed Encephalopathy After Acute Carbon Monoxide Poisoning.

Objective: To study the correlation between the adenosine triphosphate (ATP) content in the hippocampus of rats and delayed encephalopathy after acute carbon monoxide (CO) poisoning. Methods: A total of 40 male Wistar rats weighing 180-230g, in accordance with the random number table, were selected and divided into the delayed encephalopathy after acute carbon monoxide poisoning (DEACMP: Rats with cognitive impairment after carbon monoxide poisoning) group (n = 32) and the control group (n = 8). A DEACMP rat model was generated by inhalation of CO. The Morris water maze evaluated the ability to learn and memorize in rats. The changes in neurons in the hippocampus of the rats were observed by hematoxylin-eosin (HE) staining. Lastly, the ATP content in the hippocampus of the rats was measured by high-performance liquid chromatography (HPLC). Results: The ATP content of the experimental group was significantly higher than that of the control group in the hippocampus of the rat model, so the difference was statistically significant (P < 0.05); the intra-group comparison was made for the ATP content in the experimental group, and the difference was statistically significant as group 21d > group 14d > group 7d (P < 0.05); and no significant difference was found between group 21d and group 28d (P > 0.05). Conclusion: The changes in the ATP content in the hippocampus of the rats are correlated with the occurrence of delayed encephalopathy after acute carbon monoxide poisoning; it may take part in the pathogenesis of DEACMP. This offers some elicitation to the prevention and treatment of the disease.

Chest Pain in a Young Male with Carbon Monoxide Poisoning and Substance Abuse: A Case Report and Literature Review.

BACKGROUND: Carbon monoxide (CO) poisoning is the leading cause of poisoning-related deaths in the United States. In addition, myocardial infarction (MI) due to CO poisoning in a young, healthy adult is rare. On the other hand, smokeless tobacco, processed in various forms, is a controversial coronary heart disease (CHD) risk factor. CASE REPORT: In this study, we describe a 29-year-old man who presented with acute chest pain following a night of smoking tobacco and using smokeless tobacco in the presence of carbon monoxide poisoning. ST-segment elevation was observed on an electrocardiogram, and echocardiography revealed akinesia. In addition, cardiac markers were elevated. In this particular instance, thrombolytic therapy demonstrated successful outcomes. CONCLUSIONS: We believe the case and discussion could shed light on the emergency department management of such individuals. We advise clinicians to consider the possibility of coronary heart disease in carbon monoxide poisoning patients and to obtain a baseline electrocardiogram and cardiac markers.

LncRNA CRNDE Deteriorates Delayed Encephalopathy After Acute Carbon Monoxide Poisoning to Inactivate AKT/GSK3ß/ß-catenin Pathway via miR-212-5p.

Delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) is the most serious sequel of acute CO poisoning, with structure or function injury of the brain. LncRNA colorectal neoplasia differentially expressed (CRNDE) aberrant expression was involved in nerve cell injury; however, the mechanism of CRNDE in DEACMP remains elusive. CO poisoning model of Sprague-Dawley rats was established. Neurological function was measured by Morris water maze (MWM) testing. Histopathological condition of brain and hippocampus tissues was observed by hematoxylin and eosin (H&E), Nissl, and TUNEL staining. Pro-inflammatory cytokine levels were evaluated by enzyme-linked immunosorbent assay (ELISA). Oxidative damage and apoptosis markers were determined by related detection assays. Cell apoptosis were evaluated by flow cytometry analysis. Luciferase report and RNA immunoprecipitation (RIP) assays were employed to identify the binding relationship of CRNDE and miR-212-5p. CRNDE was significantly increased in CO poisoning animal model and oxygen-glucose deprivation (OGD) group, while that of miR-212-5p was decreased. CRNDE knockdown repressed the histopathological damage and apoptosis of brain and hippocampus tissues. Besides, CRNDE suppressed the AKT/GSK3ß/ß-catenin signaling pathway via targeting miR-212-5p. Furthermore, the protective effects of CRNDE silencing on brain tissue injury and apoptosis and AKT/GSK3ß/ß-catenin signaling pathway were reversed by inhibition of miR-212-5p in CO poisoning model. Collectively, CRNDE, serving as a sponge of miR-212-5p, aggravated the injury and apoptosis of brain and hippocampus tissues through regulating AKT/GSK3ß/ß-catenin signaling pathway under the CO-poisoning and OGD-treated model, suggesting a selected therapeutic target of DEACMP.

Charcoal burning is associated with a higher risk of delayed neurological sequelae after domestic carbon monoxide poisoning in South China: A retrospective cohort study.

BACKGROUNDS: Delayed neurological sequelae (DNS) are a severe complication of carbon monoxide poisoning (COP) and high predisposing rates of disability and mortality, yet the relationship between exposure factors and DNS remains unknown. The aim was to investigate the association between domestic sources of COP and DNS. METHODS: Patients diagnosed with COP between December 2016 and November 2021 were included and divided into two groups according to their sources of poisoning and the endpoint outcome was analyzed by logistic regression before and after propensity score matching (PSM). RESULTS: Overall, medical data from 314 patients were analyzed. In multivariate logistic regression, advanced age (adjusted odds ratio (AOR): 1.028, 95% CI: 1.008-1.049, P = 0.007), longer duration of exposure to the first treatment of hyperbaric oxygen (HBO) (AOR: 1.081, 95% CI: 1.036-1.127, P = 0.001), and intoxication by charcoal burning (AOR: 3.24, 95% CI: 1.208-8.69, P = 0.019) were associated with a higher risk of developing DNS. After 1:1 PSM, the outcomes also revealed that charcoal burning intoxication (odds ratio (OR): 8.396, 95% CI: 3.342-21.095, P<0.001) was associated with greater odds of DNS. CONCLUSIONS: This study indicates that domestic COP caused by charcoal burning is more likely to trigger DNS than gas-emitting heaters.

Carbon Monoxide poisoning and Air Embolism following Hysteroscopic Myomectomy: a case report.

INTRODUCTION: Uterine myomas are the most common benign uterine tumors. Hysteroscopic myomectomy has grown as a standard minimally invasive surgical procedure, but this technique is not free from complications. CASE: An hysteroscopic myomectomy was performed on a 38 years-old woman. During the awakening after the procedure, she presented focal neurological deficits, thus arterial blood gas test and total body computerized tomography (CT) scan were urgently carried out. They revealed a very high carboxyhemoglobin level and abdominal venous air embolism. The patient stayed in Trendelenburg position and under mechanical ventilation with 100% oxygen concentration. Fortunately, a few hours later she was fully awake and was able to be successfully extubated, being discharged to the surgical ward three days later fully recovered. CONCLUSION: Carbon monoxide poisoning during hysteroscopic resection is a rare but potentially fatal complication that anesthetists, gynecologists, and critical care physicians should be aware of.

Three cases of clinically significant inaccurate carboxyhemoglobin measurement.

Background: Clinicians often rely on measurement of carboxyhemoglobin (COHb) to confirm or rule out a diagnosis of carbon monoxide (CO) poisoning. Methods: We report two cases of false negative COHb in patients with CO poisoning and one case of false positive COHb in a patient without CO poisoning. Results: In the first case, a 20-year-old male developed headache, confusion, and near-syncope while operating a gasoline-powered pressure washer in an enclosed space. In the emergency department (ED), his COHb was 1.8%, but this level was disregarded, and he was referred for hyperbaric oxygen. His COHb just before hyperbaric oxygen was 4.1%, and later analysis of his blood collected at ED arrival revealed a COHb of 20.1%. The referral ED blood gas machine calibration and controls were within specification. In the second case, a 45-year-old male presented with several others to the ED with symptoms of CO poisoning after exposure at a conference. All others had elevated COHb levels, but his COHb was 2%. He was discharged but returned shortly with continued symptoms and requested his COHb be repeated. The repeat COHb was 17% (84 minutes after the first). After three hours of oxygen, his COHb was 7%. In the final case, an 83-year-old non-smoking male presented to an ED with breathlessness and tachypnea and was diagnosed with COVID-19 pneumonia. His COHb was 7.1%, but he reported living in an all-electric home. Another adult who lived with him and rode with him to the ED was asymptomatic and had a COHb of 3%. Later, COHb of 1.9% was measured from blood collected at ED arrival, and gas chromatography/mass spectrometry confirmed this result (2%). Conclusions: COHb levels are not always accurate. Clinicians should use clinical judgment to manage their patients, including rejecting laboratory values that do not fit the clinical situation.

Highly Selective and Low-Power Carbon Monoxide Gas Sensor Based on the Chain Reaction of Oxygen and Carbon Monoxide to WO3.

Carbon monoxide (CO) poisoning can easily occur in industrial and domestic settings, causing headaches, loss of consciousness, or death from overexposure. Commercially available CO gas sensors consume high power (typically 38 mW), whereas low-power gas sensors using nanostructured materials with catalysts lack reliability and uniformity. A low-power (1.8 mW @ 392 °C), sensitive, selective, reliable, and practical CO gas sensor is presented. The sensor adopts floated WO3 film as a sensing material to utilize the unique reaction of lattice oxide of WO3 with CO gas. The sensor locally modulates the electron concentration in the WO3 film, allowing O2 and CO gases to react primarily in different sensing areas. Electrons generated by the CO gas reaction can be consumed for O2 gas adsorption in a remote area, and this promotes the additional reaction of CO gas, boosting sensitivity and selectivity. The proposed sensor exhibits a 39.5 times higher response than the conventional resistor-type gas sensor fabricated on the same wafer. As a proof of concept, sensors with In2O3 film are fabricated, and the proposed sensor platform shows no advantage in detecting CO gas. Fabrication of the proposed sensor is reproducible and inexpensive due to conventional silicon-based processes, making it attractive for practical applications.

Severe chronic Carboxyhemoglobinemia and polycythemia due to smoking hookah.

Acute carbon monoxide (CO) poisoning due to smoking hookah has been reported and may present similarly to other causes of acute carbon monoxide poisoning with nausea, headache, and loss of consciousness [1]. In the acute poisoned patient, immediate removal from the carbon monoxide source is paramount in addition to administration of oxygen and possible hyperbaric oxygen therapy (HBO) in certain situations. However, cases of chronic CO poisoning, treatment options, and long-term adverse health effects are far less reported but may include atherosclerosis and vague neurologic symptoms [2]. We present a case of a patient who chronically smoked hookah creating a condition of chronic carboxyhemoglobinemia which was discovered during work up for unexplained polycythemia. While being seen in the hematology clinic, he was found to have a blood carboxyhemoglobin of level 33.6% despite being asymptomatic. This is the highest recorded hookah-related carboxyhemoglobin concentration in the medical literature; and the significant chronic carboxyhemoglobinemia explained his polycythemia. This case illustrates that a social history is crucial when assessing the patient with severe carboxyhemoglobinemia as HBO is not indicated in chronic CO poisoning in an asymptomatic patient.

Veno-venous extracorporeal blood phototherapy increases the rate of carbon monoxide (CO) elimination in CO-poisoned pigs.

BACKGROUND AND OBJECTIVES: Carbon monoxide (CO) inhalation is the leading cause of poison-related deaths in the United States. CO binds to hemoglobin (Hb), displaces oxygen, and reduces oxygen delivery to tissues. The optimal treatment for CO poisoning in patients with normal lung function is the administration of hyperbaric oxygen (HBO). However, hyperbaric chambers are only available in medical centers with specialized equipment, resulting in delayed therapy. Visible light dissociates CO from Hb with minimal effect on oxygen binding. In a previous study, we combined a membrane oxygenator with phototherapy at 623 nm to produce a "mini" photo-ECMO (extracorporeal membrane oxygenation) device, which improved CO elimination and survival in CO-poisoned rats. The objective of this study was to develop a larger photo-ECMO device ("maxi" photo-ECMO) and to test its ability to remove CO from a porcine model of CO poisoning. STUDY DESIGN/MATERIALS AND METHODS: The "maxi" photo-ECMO device and the photo-ECMO system (six maxi photo-ECMO devices assembled in parallel), were tested in an in vitro circuit of CO poisoning. To assess the ability of the photo-ECMO device and the photo-ECMO system to remove CO from CO-poisoned blood in vitro, the half-life of COHb (COHb-t1/2 ), as well as the percent COHb reduction in a single blood pass through the device, were assessed. In the in vivo studies, we assessed the COHb-t1/2 in a CO-poisoned pig under three conditions: (1) While the pig breathed 100% oxygen through the endotracheal tube; (2) while the pig was connected to the photo-ECMO system with no light exposure; and (3) while the pig was connected to the photo-ECMO system, which was exposed to red light. RESULTS: The photo-ECMO device was able to fully oxygenate the blood after a single pass through the device. Compared to ventilation with 100% oxygen alone, illumination with red light together with 100% oxygen was twice as efficient in removing CO from blood. Changes in gas flow rates did not alter CO elimination in one pass through the device. Increases in irradiance up to 214 mW/cm2 were associated with an increased rate of CO elimination. The photo-ECMO device was effective over a range of blood flow rates and with higher blood flow rates, more CO was eliminated. A photo-ECMO system composed of six photo-ECMO devices removed CO faster from CO-poisoned blood than a single photo-ECMO device. In a CO-poisoned pig, the photo-ECMO system increased the rate of CO elimination without significantly increasing the animal's body temperature or causing hemodynamic instability. CONCLUSION: In this study, we developed a photo-ECMO system and demonstrated its ability to remove CO from CO-poisoned 45-kg pigs. Technical modifications of the photo-ECMO system, including the development of a compact, portable device, will permit treatment of patients with CO poisoning at the scene of their poisoning, during transit to a local emergency room, and in hospitals that lack HBO facilities.