Carbon monoxide and mitochondria: Cell energy and fate control.

Carbon monoxide (CO) is a ubiquitously produced endogenous gas in mammalian cells and is involved in stress response being considered as a cytoprotective and homeostatic factor. In the present review, the underlying mechanisms of CO are discussed, in particular CO's impact on cellular metabolism affecting cell fate and function. One of the principal signaling molecules of CO is reactive oxygen species (ROS), particularly hydrogen peroxide, which is mainly generated at the mitochondrial level. Likewise, CO acts on mitochondria modulating oxidative phosphorylation and mitochondria quality control, namely mitochondrial biogenesis (mitobiogenesis) and mitophagy. Other metabolic pathways are also involved in CO's mode of action such as glycolysis and pentose phosphate pathway. The review ends with some new perspectives on CO Biology research. Carboxyhemoglobin (COHb) formation can also be implicated in the CO mode of action, as well as its potential biological role. Finally, other organelles such as peroxisomes hold the potential to be targeted and modulated by CO.

Carboxyhemoglobin as Potential Biomarker for Cardiac Surgery Associated Acute Kidney Injury.

OBJECTIVES: Carboxyhemoglobin (CO-Hb) is a marker of hemolysis and inflammation, both risk factors for cardiac surgery-associated AKI (CSA-AKI). However, the association between CO-Hb and CSA-AKI remains unknown. DESIGN: A retrospective cohort study. SETTING: Tertiary university-affiliated metropolitan hospital: single center. PARTICIPANTS: Adult on-pump cardiac surgery patients from July 2014 to June 2022 (N = 1,698). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were stratified into quartiles based on CO-Hb levels at intensive care unit (ICU) admission. A progressive increased risk of CSA-AKI was observed with higher CO-Hb levels at ICU admission. On multivariable logistic regression analysis, the highest quartile (CO-Hb ≥ 1.4%) showed an independent association with the occurrence of CSA-AKI (odds ratio 1.45 compared to the lowest quartile [CO-Hb < 1.0%], 95% CI 1.023-2.071; p = 0.038). Compared to patients with CO-Hb <1.4%, patients with CO-Hb ≥ 1.4% at ICU admission had significantly higher postoperative creatinine (135 vs 116 µmol/L, p < 0.001), higher rates of postoperative RRT (6.7% vs 2.3%, p < 0.001) and AKI (p < 0.001) on univariable analysis and shorter time to event for AKI or death (p < 0.001). CONCLUSIONS: CO-Hb ≥ 1.4% at ICU admission is an independent risk factor for CSA-AKI, which is easily obtainable and available on routine arterial blood gas measurements. Thus, CO-Hb may serve as a practical and biologically logical biomarker for risk stratification and population enrichment in trials of CSA-AKI prevention.

Development of a risk prediction nomogram for delayed neuropsychiatric sequelae in patients with acute carbon monoxide poisoning.

OBJECTIVES: Delayed neuropsychiatric sequelae (DNS) are critical complications following acute carbon monoxide (CO) poisoning that can substantially affect the patient's life. Identifying high-risk patients for developing DNS may improve the quality of follow-up care. To date, the predictive DNS determinants are still controversial. Consequently, this study aimed to construct a practical nomogram for predicting DNS in acute CO-poisoned patients. METHODS: This retrospective study was conducted on patients with acute CO poisoning admitted to the Tanta University Poison Control Center (TUPCC) from December 2018 to December 2022. Demographic, toxicological, and initial clinical characteristics data, as well as laboratory investigation results, were recorded for the included patients. After acute recovery, patients were followed up for six months and categorized into patients with and without DNS. RESULTS: Out of 174 enrolled patients, 38 (21.8%) developed DNS. The initial Glasgow Coma Scale (GCS), carboxyhemoglobin (COHb) level, CO exposure duration, oxygen saturation, PaCO2, and pulse rate were significantly associated with DNS development by univariate analysis. However, the constructed nomogram based on the multivariable regression analysis included three parameters: duration of CO exposure, COHb level, and GCS with adjusted odd ratios of 1.453 (95% CI: 1.116-1.892), 1.262 (95% CI: 1.126-1.415), and 0.619 (95% CI: 0.486-0.787), respectively. The internal validation of the nomogram exhibited excellent discrimination (area under the curve [AUC] = 0.962), good calibration, and satisfactory decision curve analysis for predicting the DNS probability. CONCLUSIONS: The proposed nomogram could be considered a simple, precise, and applicable tool to predict DNS development in acute CO-poisoned patients.

Biochemical parameters and clinical outcomes of carbon monoxide poisoning in special groups: children, pregnant women, and the elderly.

OBJECTIVE: Carbon monoxide (CO), a toxic gas, poses a significant threat to human health. Children, pregnant women, and elderly individuals are particularly vulnerable to this toxicity. This study aims to evaluate the demographic and clinical characteristics of pediatric, pregnant, and geriatric patients. PATIENTS AND METHODS: The study included pediatric, pregnant, and geriatric patients with a confirmed diagnosis of CO poisoning, excluding those with complete file data and those with carboxyhemoglobin (COHb) levels below 5% (for children and pregnant patients) and 10% (for elderly patients). Patients aged < 18 years, > 65 years, and pregnant patients admitted to the adult and pediatric emergency departments were included in the study; statistical analyses were conducted using SPSS Inc., with a p-value of < 0.05 considered statistically significant. RESULTS: For pediatric patients, a statistically significant difference was observed between the two groups in terms of their main complaints, which were primarily attributed to neurological and general symptoms. A positive correlation was found between follow-up time and several factors, including white blood cell (WBC) count and troponin, lactate, lactate dehydrogenase (LDH), and COHb levels. For pregnant patients, no in-hospital mortality was observed in the patients included in this study. A significant negative correlation was identified between age and both COHb and hemoglobin (Hb) levels. A strong positive correlation was found between the COHb levels and hospital follow-up time. For elderly patients, no significant differences were found between the two treatment modalities. Notably, higher COHb levels on admission were associated with a more fatal in-hospital course, with COHb levels > 40% of all patients requiring intubation. CONCLUSIONS: Vulnerable populations are at increased risk of exposure to CO, and the study results emphasize the necessity of heightened awareness and preventive measures to safeguard these individuals from CO poisoning.

The Relationship between Fragmented QRS and Myocardial Injury in Patients with Acute Carbon Monoxide Poisoning.

Background and Objectives: Carbon monoxide (CO) intoxication is one of the most common causes of poisoning-related deaths and complications. Myocardial injury is an important complication of CO poisoning. In our study, we aimed to evaluate the relationship between the presence and prevalence of fragmented QRS (fQRS) and myocardial injury in patients with CO intoxication. Materials and Methods: We retrospectively evaluated patients who presented to the emergency department of our tertiary care center with CO intoxication between January 2020 and December 2023. In our study, we performed subgroup analyses according to the presence of myocardial injury and fQRS. We evaluated the parameters and risk factors associated with myocardial injury. Results: Myocardial injury was detected in 44 patients, and fQRS was detected in 38 patients. In the myocardial injury (+) group, the fQRS rate was 38.6%, and the median number of leads with fQRS was 3 (2-6) and was significantly higher than in the myocardial injury (-) group (p < 0.001). We found that carboxyhemoglobin had a significant positive correlation with troponin (p = 0.001) and pro-B-type natriuretic peptide (proBNP) (p = 0.009). As a result of multivariate analysis, we determined that age, creatinine, proBNP, fQRS, and ≥3 leads with fQRS are independent risk factors for myocardial injury. Conclusions: Myocardial injury in CO intoxication patients is associated with proBNP, the presence of fQRS, and the number of leads with fQRS. Age, creatinine level, proBNP, the presence of fQRS, and ≥3 leads with fQRS are independent risk factors for myocardial injury in patients with CO intoxication.

Forensic utility of carboxyhemoglobin levels in postmortem spleen specimens in South Korea.

In order to determine whether CO poisoning was the definitive cause of death, the concentration of carboxyhemoglobin (COHb) in spleen specimens was analyzed using a gas chromatography-thermal conductivity detector. 125 cases of forensic autopsy reports containing COHb analysis requests were analyzed and subdivided into two groups, improbable and highly probable of CO intoxication. In the first group which consists of 100 cases, the results of COHb analysis were negative, and the circumstances of death, as well as the postmortem findings could not validate the exposure to CO. In the second group which consists of 25 cases, the results of COHb were positive, and both postmortem findings and circumstances of death confirmed the exposure to CO. In the cases of indoors and vehicle fires or those including the use of briquettes, COHb levels reached 43.1-97.5 %, whereas in individuals without any feature of CO poisoning had COHb level high as 29.8 %. However, certain cases without any connection to fire nor CO exposure also contained significant amount of CO based on post-mortem analysis. This study focuses on cases without any relationship to fire or CO and proves that COHb levels below 30 % may be considered as a contributing factor to but not exclusively as the cause of death.

Effects of acute carbon monoxide poisoning on liver damage and comparisons of related oxygen therapies in a rat model.

Acute carbon monoxide (CO) poisoning may cause liver damage and liver dysfunction. Therefore, in this study, we aimed to compare the efficiency of normobaric oxygen (NBO) and high-flow nasal cannula oxygen (HFNCO) treatments on liver injury. For that purpose, 28 male Wistar albino rats were divided into four groups (Control, CO, CO + NBO, and CO + HFNCO). The control group was allowed to breath room air for 30 min. Acute CO poisoning in CO, CO + NBO, CO + HFNCO was induced by CO exposure for 30 min. Thereafter, NBO group received 100% NBO with reservoir mask for 30 min. HFNCO group received high-flow oxygen through nasal cannula for 30 min. At the end of the experiment, all animals were sacrificed by cardiac puncture under anesthesia. Serum liver function tests were measured. Liver tissue total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels, tissue histomorphology and immunoexpression levels of Bax, Caspase 3, TNF-α, IL-1ß, and NF-κB were also examined. Our observations indicated that acute CO poisoning caused significant increases in blood COHb, serum aminotransferase (AST), alanine aminotransferase (ALT0, alkaline phosphatase (ALP), total protein, albumin, and globulin levels but a decrease in albumin to globulin ratio (all, p < 0.05). Furthermore, acute CO poisoning significantly increased the OSI value, and the immunoexpresssion of Bax, Caspase 3, TNF-α, IL-1ß, and NF-κB in liver tissue (all, p < 0.05). These pathological changes in serum and liver tissue were alleviated through both of the treatment methods. In conclusion, both the NBO and HFNCO treatments were beneficial to alleviate the acute CO poisoning associated with liver injury and dysfunction.

Beneficial Effects of Oral Carbon Monoxide on Doxorubicin-Induced Cardiotoxicity.

BACKGROUND: Doxorubicin and other anthracyclines are crucial cancer treatment drugs. However, they are associated with significant cardiotoxicity, severely affecting patient care and limiting dosage and usage. Previous studies have shown that low carbon monoxide (CO) concentrations protect against doxorubicin toxicity. However, traditional methods of CO delivery pose complex challenges for daily administration, such as dosing and toxicity. To address these challenges, we developed a novel oral liquid drug product containing CO (HBI-002) that can be easily self-administered by patients with cancer undergoing doxorubicin treatment, resulting in CO being delivered through the upper gastrointestinal tract. METHODS AND RESULTS: HBI-002 was tested in a murine model of doxorubicin cardiotoxicity in the presence and absence of lung or breast cancer. The mice received HBI-002 twice daily before doxorubicin administration and experienced increased carboxyhemoglobin levels from a baseline of ≈1% to 7%. Heart tissue from mice treated with HBI-002 had a 6.3-fold increase in CO concentrations and higher expression of the cytoprotective enzyme heme oxygenase-1 compared with placebo control. In both acute and chronic doxorubicin toxicity scenarios, HBI-002 protected the heart from cardiotoxic effects, including limiting tissue damage and cardiac dysfunction and improving survival. In addition, HBI-002 did not compromise the efficacy of doxorubicin in reducing tumor volume, but rather enhanced the sensitivity of breast 4T1 cancer cells to doxorubicin while simultaneously protecting cardiac function. CONCLUSIONS: These findings strongly support using HBI-002 as a cardioprotective agent that maintains the therapeutic benefits of doxorubicin cancer treatment while mitigating cardiac damage.

Postmortem concentrations for total blood carbon monoxide (TBCO) as a novel biomarker for carbon monoxide (CO) poisonings.

Total blood carbon monoxide (TBCO) showed promising results in improving accuracy of CO determinations in blood and presenting better stability to different storage conditions. Therefore, it was proposed as an alternative biomarker to carboxyhemoglobin (COHb) for CO poisoning diagnosis. However, given that current interpretation reference values exist for COHb only, it is difficult to implement TBCO analysis in routine. Therefore, we aimed at determining TBCO reference values for postmortem CO poisoning cases. A previously validated method for TBCO analysis via gas chromatography-mass spectrometry was applied to cardiac, peripheral, cranial and spleen blood samples collected from 92 autopsies. Autopsy cases included 21 non-CO-related and 71 CO-related cases with varying postmortem intervals (PMIs). Statistical analyses were performed using statistical software R Studio. When comparing lower to higher PMIs for non-CO-related cases, no significant differences were found, which suggests that CO formation or degradation at low PMIs does not occur. Spleen blood showed potential as an alternative matrix to CO determinations in cases with sample availability issues but needs to be evaluated for CO-positive cases. Results for cardiac blood in CO-related autopsies showed a positive correlation between COHb and TBCO values (R = 0.78). This value is lower than what is found in the literature, suggesting that even though COHb and TBCO are correlated, a potential underestimation of the true CO exposure might occur if only COHb values are taken into consideration. Samples were divided into CO exposure groups based on COHb concentrations, and with the data obtained, classification into the following TBCO concentration groups is proposed: no significant CO exposure case <6 µmol/mL, medium CO exposure case 6-20 µmol/mL and high CO exposure case >20 µmol/mL. Even if a higher number of samples in each group would enable to increase the confidence, these results are very promising and highlight the importance of TBCO measurement.

Carboxyhemoglobin in Cardiac Surgery Patients and Its Association with Risk Factors and Biomarkers of Hemolysis.

BACKGROUND: Cardiac surgery with cardiopulmonary bypass (CPB) is associated with hemolysis. Yet, there is no easily available and frequently measured marker to monitor this hemolysis. However, carboxyhemoglobin (CO-Hb), formed by the binding of carbon monoxide (a product of heme breakdown) to hemoglobin, may reflect such hemolysis. We hypothesized that CO-Hb might increase after cardiac surgery and show associations with operative risk factors and indirect markers for hemolysis. METHODS: We conducted a retrospective descriptive cohort study of data from on-pump cardiac surgery patients. We analyzed temporal changes in CO-Hb levels and applied a generalized linear model to assess patient characteristics associated with peak CO-Hb levels. Additionally, we examined their relationship with red blood cell (RBC) transfusion and bilirubin levels. RESULTS: We studied 38,487 CO-Hb measurements in 1735 patients. CO-Hb levels increased significantly after cardiac surgery, reaching a peak CO-Hb level 2.1 times higher than baseline ( P < .001) at a median of 17 hours after the initiation of surgery. Several factors were independently associated with higher peak CO-Hb, including age ( P < .001), preoperative respiratory disease ( P = .001), New York Heart Association Class IV ( P = .019), the number of packed RBC transfused ( P < .001), and the duration of CPB ( P = .002). Peak CO-Hb levels also significantly correlated with postoperative total bilirubin levels (Rho = 0.27, P < .001). CONCLUSIONS: CO-Hb may represent a readily obtainable and frequently measured biomarker that has a moderate association with known biomarkers of and risk factors for hemolysis in on-pump cardiac surgery patients. These findings have potential clinical implications and warrant further investigation.

Waterpipe vs non-Waterpipe carbon monoxide poisoning: Comparison of patient characteristics, clinical presentation and outcomes.

OBJECTIVE: The aim of this study is to describe the difference between carboxyhemoglobin (CO-Hb) acute poisoning caused by waterpipe vs non-waterpipe exposures as they relate to demographics, clinical presentations and outcome of patients. DESIGN: Retrospective cohort study conducted in the Emergency Department (ED) at the Lebanon. PATIENTS: All adult patients presenting with a CO-Hb level ≥ 10 between January 2019 and August 2023 with exposure types stratified as waterpipe or non-waterpipe. MEASUREMENTS AND MAIN RESULTS: 111 ED visits were identified. Among these, 73.9% were attributed to waterpipe exposure, while 26.1% were non-waterpipe sources. These included cigarette smoking (17.2%), burning coal (24.1%), fire incidents (3.6%), gas leaks (6.9%), heating device use (10.3%), and undocumented sources (37.9%). Patients with waterpipe-related carbon monoxide exposure were younger (41 vs 50 years, p = 0.015) women (63.4 vs 41.4%, p = 0.039) with less comorbidities compared to non-waterpipe exposures (22.2 vs 41.4%, p = 0.047). Waterpipe smokers were more likely to present during the summer (42.7 vs 13.8%, p = 0.002) and have shorter ED length of stays (3.9 vs 4.5 h, p = 0.03). A higher percentage of waterpipe smokers presented with syncope (52.4 vs 17.2%, p = 0.001) whereas cough/dyspnea were more common in non-waterpipe exposures (31 vs 9.8%, p = 0.006). The initial CO-Hb level was found to be significantly higher in waterpipe exposure as compared to non-waterpipe (19.7 vs 13.7, p = 0.004). Non-waterpipe exposures were more likely to be admitted to the hospital (24.1 vs 4.9%, p = 0.015). Waterpipe smokers had significantly higher odds of experiencing syncope, with a 5.74-fold increase in risk compared to those exposed to non-waterpipe sources (p = 0.004) irrespective of their CO-Hb level. Furthermore, males had significantly lower odds of syncope as compared to females, following carbon monoxide exposure (aOR 0.31, 95% CI 0.13-0.74). CONCLUSION: CO-Hb poisoning related to waterpipe smoking has distinctive features. Syncope is a commonly associated presentation that should solicit a focused social history in communities where waterpipe smoking is common. Furthermore, CO-Hb poisoning should remain on the differential in patients presenting with headache, syncope, dizziness, vomiting or shortness of breath, even outside of the non-waterpipe exposure peaks of winter season.

Fire deaths in Cape Town, South Africa: A retrospective review of medico-legal and toxicological findings (2006 - 2018).

BACKGROUND: In South Africa, fire-related deaths are common, particularly within dense informal housing settlements. Published data on deaths from fire incidents in Cape Town is sparse. Additionally, little emphasis has been placed on the role of toxicological investigations in these deaths, despite the known risk of alcohol and drug impairment to burn injury. METHODS: A retrospective, descriptive analysis of post-mortem case reports from Salt River Mortuary was conducted to investigate all deaths in which fires were involved in the west metropole of Cape Town, between 2006 to 2018. Demographic, circumstantial, and toxicological data were analyzed using R software. RESULTS: In total 1370 fire deaths occurred over 13 years, with a mean of 106 (SD ± 18) cases per annum (≈3% of the annual caseload and a mortality rate of 5.5 per 100,000). Males (70.4%), adults (mean=30.7 years), and toddlers (1-4 years old) were notably at risk. Deaths typically occurred in the early morning (00h00 - 06h00) (45.7%), during winter (32.1%), and in lower socioeconomic areas with highly dense informal settlements (65.6%), with 29% of deaths occurring in multi-fatality incidents. Ethanol was detected (≥0.01 g/100 mL) in 55.1% of cases submitted for analysis (71.5%), with a mean of 0.18 g/100 mL, and with 93.8% of positive cases > 0.05 g/100 mL. Carboxyhaemoglobin (COHb) analysis was requested in 76.4% of cases, with 57% of cases having a %COHb of ≥ 20%. Toxicology results (for drugs other than ethanol) from the national laboratory were outstanding in 34.4% of the cases at the conclusion of the study. BAC and %COHb were significantly higher in deaths from burns and smoke inhalation (usually accidents) than deaths from combined trauma and burns (typically homicides). Fire deaths with high COHb levels were more likely to display cherry-red discoloration (OR=3.1) and soot in the airways (OR=2.7) at autopsy. CONCLUSION: This article provides an updated description of fire deaths in the west metropole of Cape Town. The importance of BAC and COHb testing in these cases was noted, and the authors call for an investigation of the role of drug impairment (specifically frequently misused drugs methamphetamine and methaqualone) as a risk factor in these deaths. Areas of high-density informal settlements, where open flames are used to heat, light, and cook, were noted as high risk.

From suicide to accident - Case report - The significance of the medico-legal autopsies.

INTRODUCTION: Suicide is the intentional and voluntary act of destroying one's own life, while an accident is an unintended event that involuntarily causes injury to one's health or destruction of life. CASE PRESENTATION: We report a case of a 54-year-old male who was found in a forest in late November, approximately 500 m away from his car. He was positioned bent over a trunk of a tree with his head beneath the rest of his body. His pants were down to his knees, and there were soiled blades of grass and leaves on his body. Investigation of the case circumstances revealed that he had attempted suicide by carbon monoxide poisoning, using a hose connected to the exhaust pipe and running it through the window into the cabin. Window on the driver's side was broken with glass particles on the driver's seat. Wrappers from "Rivotril" tablets, a generic benzodiazepine, were also found in the car. Autopsy revealed the following: postmortem hypostasis was of a cherry red color and well pronounced on the upper part of the front of the body and face. Numerous bruises, contusions, and erosions were present all over the body. Frostbites were especially pronounced in the knees and elbows area. The synovial membranes were partially bloodstained and reddish in color. Opening the stomach revealed erosions of the gastric mucosa (Wischnewsky sign). Chemical toxicological analysis detected presence of benzodiazepines and carboxyhemoglobin (25%). CONCLUSION: Based on the autopsy findings, chemical toxicological analyses, and investigation of the case circumstances, it has been concluded that the death occurred due to the combined effects of hypothermia, postural asphyxia and carboxyhemoglobin and benzodiazepine intoxication. The manner of death in this case is a combination of accidental and suicidal, as the victim attempted suicide but ultimately died due to exposure to low external temperature.

Duplicate measures of hemoglobin mass within an hour: feasibility, reliability, and comparison of three devices in supine position.

Duplicate measure of hemoglobin mass by carbon monoxide (CO)-rebreathing is a logistical challenge as recommendations prompt several hours between measures to minimize CO-accumulation. This study investigated the feasibility and reliability of performing duplicate CO-rebreathing procedures immediately following one another. Additionally, it was evaluated whether the obtained hemoglobin mass from three different CO-rebreathing devices is comparable. Fifty-five healthy participants (22 males, 23 females) performed 222 duplicate CO-rebreathing procedures in total. Additionally, in a randomized cross-over design 10 participants completed three experimental trials, each including three CO-rebreathing procedures, with the first and second separated by 24 h and the second and third separated by 5-10 min. Each trial was separated by >48 h and conducted using either a glass-spirometer, a semi-automated electromechanical device, or a standard three-way plastic valve designed for pulmonary measurements. Hemoglobin mass was 3 ± 22 g lower (p < 0.05) at the second measure when performed immediately after the first with a typical error of 1.1%. Carboxyhemoglobin levels reached 10.9 ± 1.3%. In the randomized trial, hemoglobin mass was similar between the glass-spirometer and three-way valve, but ∼6% (∼50 g) higher for the semi-automated device. Notably, differences in hemoglobin mass were up to ∼13% (∼100 g) when device-specific recommendations for correction of CO loss to myoglobin and exhalation was followed. In conclusion, it is feasible and reliable to perform two immediate CO-rebreathing procedures. Hemoglobin mass is comparable between the glass-spirometer and the three-way plastic valve, but higher for the semi-automated device. The differences are amplified if the device-specific recommendations of CO-loss corrections are followed.

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.

Elevated methemoglobin levels in patients treated with high-dose hydroxocobalamin.

OBJECTIVE: The aim of this study was to assess the impact of hydroxocobalamin (OHCbl) infusion on arterial blood gas and oximetry values in patients with vasoplegic syndrome. METHODS: Blood samples collected from 95 patients receiving OHCbl infusion were assayed using the ABL90 FLEX Plus blood gas analyzer for the concentration of methemoglobin (MetHb), total hemoglobin (tHb), carboxyhemoglobin (COHb), arterial oxygen saturation (SaO2), arterial oxygen partial pressure (PaO2), and arterial carbon dioxide partial pressure (PaCO2). Interference of OHCbl on these variables was evaluated using the measured difference between the preinfusion and postinfusion samples. RESULTS: Blood MetHb (%) measured after the infusion of OHCbl (5g) were significantly higher than the baseline levels, with a median of 4.8 (IQR, 3.0-6.5) versus 1.0 (IQR, 1.0-1.2) (P < .001). Blood COHb (%) increased from a median of 1.3 (IQR, 1.0-1.8) to 1.7 (IQR, 1.3-2.2) (P < .001) following the OHCbl infusion. No differences were seen in median levels of tHb, PaO2, PaCO2, and SaO2 between pre- and post-OHCbl treatment. CONCLUSION: The presence of OHCbl in blood clearly interfered with the oximetry measurements of the hemoglobin component fractions by falsely increasing the levels of MetHb and COHb. Blood levels of MetHb and COHb cannot be reliably determined by the co-oximetry when OHCbl is known or suspected.

Comparing high-flow nasal oxygen therapy and normobaric oxygen therapy on the treatment of carbon monoxide poisoning.

AIM: We aimed to investigate whether there is a difference in the rate of decrease in carboxyhemoglobin (COHB) values between high-flow nasal oxygen (HFNO) and normobaric oxygen (NBO) therapy. MATERIAL AND METHOD: This retrospective observational study included patients with carbon monoxide poisoning who were treated with HFNO or NBO (control group). All patients were started on NBO therapy with a non-rebreather face mask at a rate of 15 L/min. In the NBO group, NBO treatment was continued until the COHB value fell below 10%. In the HFNO group, as soon as the preparation of the HFNO device was completed, NBO treatment was terminated and HFNO treatment was started and continued until the COHB value fell below 10%. The primary outcome of the study was the difference between HFNO and NBO in terms of COHB half-life rates. RESULTS: A total of 81 patients were included in the study, 44 in the HFNO group and 37 in the NBO group. The median of COHB t1/2 values between HFNO and the NBO treatment groups were 47.3 (IQR: 25-75%: 31.5-65.4) and 46 (IQR: 25-75%: 32.3-56.2), respectively, but this difference was not statistically significant (p = 0.81). CONCLUSION: The results of this study suggest that HFNO treatment does not have a significant advantage over NBO treatment in the carbon monoxide elimination rate within the first 60 min of treatment.

Biomarkers of Waterpipe Tobacco Smoke Exposure: A Systematic Review and Meta-Analysis.

INTRODUCTION: The prevalence of waterpipe tobacco smoking is increasing globally. Biomarkers of waterpipe tobacco smoke (WTS) exposure are less studied. AIMS AND METHODS: To identify the types of biomarkers of WTS exposure and estimate changes in biomarker concentrations pre- to post-WTS exposure. PubMed, Embase, Web of Science, CINAHL Plus, PsycINFO, and Cochrane Library were searched for studies up to April 24, 2023. The types of biomarkers were identified. Random-effects models were used to estimate changes in biomarker concentrations pre- to post-WTS exposure. RESULTS: Seventy-three studies involving 3755 participants exposed to WTS (49% male, mean age: 24.8 years) and 11 types of biomarkers of WTS exposure were identified. The biomarkers included tobacco alkaloids, expired carbon monoxide (eCO), carboxyhemoglobin (COHb), tobacco-specific nitrosamines, volatile organic compounds (VOCs), polycyclic aromatic hydrocarbons (PAHs), heavy metals, unmetabolized VOCs, unmetabolized PAHs, furan metabolites, and heterocyclic aromatic amines. Compared with pre-WTS exposure, eCO (breath; mean difference [MD] 27.00 ppm; 95% confidence interval [CI]: 20.91 to 33.08), COHb (blood; MD 4.30%; 95%CI: 2.57 to 6.03), COHb (breath; MD 7.14%; 95%CI: 4.96 to 9.31), nicotine (blood; MD 8.23 ng/mL; 95%CI: 6.27 to 10.19), and cotinine (urine; MD 110.40 ng/mL; 95%CI: 46.26 to 174.54) significantly increased post-WTS exposure. CONCLUSIONS: Biomarkers of WTS exposure were systematically identified. The similarity between the biomarkers of WTS exposure and those of cigarette smoke and higher concentrations of some biomarkers post-WTS exposure underscore the need for further research on applying biomarkers in surveillance, interventions, and regulations to mitigate the harms of waterpipe tobacco smoking. IMPLICATIONS: This study provides the first comprehensive overview of biomarkers investigated and available for assessing WTS exposure and their concentration changes in the human body. Researchers can use biomarkers such as eCO, COHb, nicotine, and cotinine to measure the health risks associated with WTS exposure and objectively evaluate the effectiveness of public health interventions aimed at reducing waterpipe tobacco smoking. Public health policymaking can also be informed through increased biomarker concentrations following WTS exposure, to implement regulations and public health education campaigns on limiting or preventing waterpipe tobacco smoking.

Carboxyhemoglobin and Methemoglobin Levels and Hemolysis in Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

Hemolysis is a complication of cardiopulmonary bypass (CPB). Carboxyhemoglobin (COHb) and methemoglobin (MetHb) were suggested as potential hemolysis biomarkers. This retrospective study was based on a prospective registry aimed to determine the association of COHb and MetHb levels with hemolysis in pediatric patients <4 years old who underwent cardiac surgery with CPB. Plasma-free hemoglobin (PFH), COHb, and MetHb levels were measured before CPB; every 30 minutes during CPB; and on postoperative days 1, 2, and 3. Patients were classified into hemolysis and nonhemolysis groups based on the maximum PFH levels during CPB. A total of 193 patients were included. No significant difference was observed in the maximum COHb levels during CPB (COHb CPB ) between the hemolysis and nonhemolysis groups (1.2% [interquartile range {IQR} 0.9-1.4%] vs. 1.1% [IQR: 0.9-1.4%]; p = 0.17). The maximum MetHb levels during CPB (MetHb CPB ) were significantly higher in the hemolysis group than in the nonhemolysis group (1.3% [IQR: 1.1-1.5%] vs. 1.2% [IQR: 1.0-1.4%]; p = 0.007). Areas under the receiver operating curves of COHb CPB and MetHb CPB were 0.557 (95% confidence interval: 0.475-0.640) and 0.615 (95% confidence interval: 0.535-0.695), respectively. Therefore, the predictive ability of both hemolysis biomarkers during CPB is limited.