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.

Caracterización clínica y factores predictivos de desarrollo de síndrome neurológico tardío en la intoxicación por monóxido de carbono: estudio AMICO / Clinical features and predictors of delayed neurological syndrome in carbon monoxide poisoning: the AMICO study

Objetivos. Identificar factores pronósticos de desarrollo de síndrome neurológico tardío (SNT) después de un episodio inicial de intoxicación por monóxido de carbono (ICO), con el fin detectar precozmente a la población más susceptible y facilitar su acceso a un seguimiento específico. Métodos. Revisión retrospectiva de todos los casos de ICO que acudieron a los servicios de urgencias (SU) de 4 hospitales durante los últimos 10 años. Se analizaron datos demográficos y características clínicas en el momento del episodio. En la cohorte de pacientes con datos de seguimiento disponibles, se evaluó la aparición de SNT y su relación con diferentes variables en la exposición inicial al CO a través de técnicas de análisis multivariante. Resultados. Se identificaron 240 pacientes. La mediana de edad fue de 36,2 años (17,6-49,6). De ellos 108 (45,0%) eran hombres y 223 casos (92,9%) fueron accidentales. El nivel medio de COHb fue del 12,7% (6,2-18,7). En 44 (18,3%) episodios se disponía de datos de un seguimiento específico. En esta cohorte, 11 (25%) pacientes desarrollaron SNT. Una puntuación inicial más baja en la Escala Coma de Glasgow (GCS) (OR: 0,61, IC 95%: 0,41-0,92) fue predictor independiente del desarrollo del SNT, con un ABC en la curva COR de 0,876 (IC 95%: 0,761-0,990, p < 0,001). Conclusiones. Una puntuación inicial baja en la GCS parece ser un predictor clínico de desarrollo de SNT en la ICO. Dada la incidencia de SNT, consideramos fundamental establecer protocolos de seguimiento específico de estos pacientes tras su asistencia inicial en los SU. (AU)

Objectives. To identify predictors for developing delayed neurological syndrome (DNS) after an initial episode of carbon monoxide (CO) poisoning in the interest of detecting patients most likely to develop DNS so that they can be followed. Methods. Retrospective review of cases of CO poisoning treated in the past 10 years in the emergency departments of 4 hospitals in the AMICO study (Spanish acronym for the multicenter analysis of CO poisoning). We analyzed demographic characteristics of the patients and the clinical characteristics of the initial episode. The records of the cohort of patients with available follow-up information were reviewed to find cases of DNS. Data were analyzed by multivariant analysis to determine the relationship to characteristics of the initial exposure to CO. Results. A total of 240 cases were identified. The median (interquartile range) age of the patients was 36.2 years (17.6-49.6 years); 108 patients (45.0%) were men, and the poisoning was accidental in 223 cases (92.9%). The median carboxyhemoglobin concentration on presentation was 12.7% (6.2%-18.7%). Follow-up details were available for 44 patients (18.3%). Eleven of those patients (25%) developed DNS. A low initial Glasgow Coma Scale score predicted the development of DNS with an odds ratio (OR) of 0.61 (95% CI, 0.41-0.92) and an area under the receiver operating characteristic curve of 0.876 (95% CI, 0.761-0.990) (P <.001). Conclusions. The initial Glasgow Coma Scale score seems to be a clinical predictor of DNS after CO poisoning. We consider it important to establish follow-up protocols for patients with CO poisoning treated in hospital EDs. (AU)

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.

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.

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.

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.

Impact of methemoglobin on carboxyhemoglobin saturation measurement in fatal sodium nitrate and sodium nitrite cases.

An increase in suicide cases by sodium nitrate and sodium nitrite ingestion has been noted in the scientific literature. We report on the possible impact of nitrate/nitrite-caused methemoglobinemia on carboxyhemoglobin measurement by spectrophotometric methods. Elevated methemoglobin saturation may result in insufficient reducing agents to convert methemoglobin into deoxygenated hemoglobin, affecting the measured total hemoglobin and carboxyhemoglobin saturation. We highlight four cases where the cause of death was attributed to sodium nitrate or sodium nitrite ingestion. The possible impact of the nitrate/nitrite-caused methemoglobinemia on the carboxyhemoglobin saturation as measured by spectrophotometry is discussed. Further studies are needed to identify a causal relationship between nitrate/nitrite-caused methemoglobinemia and carboxyhemoglobin saturation as measured by spectrophotometric methods.

[Investigation of a carbon monoxide poisoning accident with a hidden source].

In June 2022, a carbon monoxide poisoning accident with hidden source occurred in a bonded gold/silver wire manufacturing enterprise in Guangzhou, causing 10 people to be poisoned, of which 1 was caused by carbon monoxide poisoning and 9 by carbon monoxide contact reaction. The symptoms were dizziness, fatigue and vomiting. After 5 to 7 h, the saturation of carboxyhemoglobin in finger pulse was 4% to 10%, and the saturation of carboxyhemoglobin in blood gas biochemical analysis was 1.9% to 5.8%. The concentration of carbon monoxide detected in the carbon borne purification plant of the enterprise was 34.46-37.26 mg/m(3). It was judged that the accident was carbon monoxide poisoning caused by carbon monoxide gas being transported to the work post along the gas transmission pipeline due to abnormal operation of the carbon borne purification plant. By investigating the source and cause of poison, this paper provides a warning for the similar process to prevent similar events, and provides a new idea for the identification of chemical poisoning risk. At the same time, it is warned that similar enterprises should fully consider the risk of poisoning under specific circumstances, strengthen equipment maintenance and repair, and prevent the occurrence of similar incidents.

Exposure levels for carbon monoxide in nuclear submarine atmosphere.

This work proposes exposure limits for carbon monoxide in the nuclear submarine environment. Linear and non-linear forms of the Coburn-Foster-Kane equation were used to evaluate carbon monoxide exposure for an environment with low oxygen content, different exposure times and crew physical activity levels. We evaluated the 90-day Continuous Exposure Guidance Level, 24-h and 1-h Emergency Exposure Guidance Levels and 10-day and 24-h Submarine Escape Action Levels. The results showed that the concentration of carbon monoxide in the environment must not exceed 9 ppm for the 90-day Continuous Exposure Guidance Level, 35 ppm for the 24-h Emergency Exposure Guidance Level, 90 ppm 1-h Emergency Exposure Guidance Level, 60 ppm for the 10-day Submarine Escape Action Level and 80 ppm for the 24-h Submarine Escape Action Level. Comparing these values with those established by the National Research Council for the United States Navy, the limits proposed by this work are verified to be lower, which may indicate a risk to the health of the crew. They also show the impact of the crew's level of physical activity on the formation of carboxyhemoglobin.

Evolution of Carboxyhemoglobin in Children Supported by Extracorporeal Membrane Oxygenation: An Observational Single-Center Study.

Carboxyhemoglobin (COHb) is potentially a novel marker of hemolysis on extracorporeal membrane oxygenation (ECMO) and may be useful as an indicator for circuit-related complication in adults, but little is known about COHb levels in children. An observational single-center study was performed between January 2018 and December 2021. Fifty-eight children were included and COHb levels were obtained along with routine blood gas analysis before, during, and after ECMO support. From the 6th hour of ECMO support, the COHb level increased relative to the pre-ECMO level, with an adjusted mean difference of 0.44 (95% confidence interval [CI], 0.26-0.62; p < 0.001) and remained higher during ECMO run and within 6 hours after weaning ( p < 0.001). Among the 18 children (31%) who experienced at least one circuit-related complication leading to a circuit change, we observed a significant decrease in COHb levels within 24 hours after the circuit change, compared with the 24 hours before (adjusted mean difference, 0.54%; 95% CI, 0.27-0.80; p < 0.001). The maximal daily COHb level was able to predict circuit-related complications within 24 hours following COHb measurement with an area under the receiver operating characteristic (ROC) curve of 0.85 (95% CI, 0.77-0.92; p < 0.001).

Carboxyhaemoglobin levels in infants with hypoxic ischaemic encephalopathy.

OBJECTIVES: Hypoxic ischaemic encephalopathy (HIE) is associated with oxidative stress. A potential marker of oxidative damage is carboxyhaemoglobin (COHb) which is the product of the reaction between carbon monoxide and haemoglobin and is routinely assessed on blood gas analysis. Our objective was to test the hypothesis that higher COHb levels would be associated with worse outcomes in infants treated for HIE. METHODS: A retrospective, observational study was performed of all infants who received whole body hypothermia for HIE at a tertiary neonatal intensive care unit between January 2018 and August 2021. For each participating infant, the highest COHb level per day was recorded for days one, three and five after birth. RESULTS: During the study period, 67 infants with a median (IQR) gestational age of 40 (38-41) weeks underwent therapeutic hypothermia for HIE. The median (IQR) COHb level on day three was higher in infants without electroencephalographic seizures (1.4 [1.1-1.4] %) compared with infants with seizures (1.1 [0.9-1.3] %, p=0.024). The median (IQR) COHb on day five was higher in infants without MRI brain abnormalities (1.4 [1.2-1.7] %) compared with infants with MRI abnormalities (1.2 [1.0-1.4] %, p=0.032). The COHb level was not significantly different between the nine infants who died compared to the infants who survived. CONCLUSIONS: COHb levels were higher in infants with HIE without seizures and in those with normal MRI brain examinations. We suggest that carbon monoxide has a potential protective role in HIE.

The Critical Assessment of Oxidative Stress Parameters as Potential Biomarkers of Carbon Monoxide Poisoning.

In conventional clinical toxicology practice, the blood level of carboxyhemoglobin is a biomarker of carbon monoxide (CO) poisoning but does not correspond to the complete clinical picture and the severity of the poisoning. Taking into account articles suggesting the relationship between oxidative stress parameters and CO poisoning, it seems reasonable to consider this topic more broadly, including experimental biochemical data (oxidative stress parameters) and patients poisoned with CO. This article aimed to critically assess oxidative-stress-related parameters as potential biomarkers to evaluate the severity of CO poisoning and their possible role in the decision to treat. The critically set parameters were antioxidative, including catalase, 2,2-diphenyl-1-picryl-hydrazyl, glutathione, thiol and carbonyl groups. Our preliminary studies involved patients (n = 82) admitted to the Toxicology Clinical Department of the University Hospital of Jagiellonian University Medical College (Kraków, Poland) during 2015-2020. The poisoning was diagnosed based on medical history, clinical symptoms, and carboxyhemoglobin blood level. Blood samples for carboxyhemoglobin and antioxidative parameters were collected immediately after admission to the emergency department. To evaluate the severity of the poisoning, the Pach scale was applied. The final analysis included a significant decrease in catalase activity and a reduction in glutathione level in all poisoned patients based on the severity of the Pach scale: I°-III° compared to the control group. It follows from the experimental data that the poisoned patients had a significant increase in level due to thiol groups and the 2,2-diphenyl-1-picryl-hydrazyl radical, with no significant differences according to the severity of poisoning. The catalase-to-glutathione and thiol-to-glutathione ratios showed the most important differences between the poisoned patients and the control group, with a significant increase in the poisoned group. The ratios did not differentiate the severity of the poisoning. The carbonyl level was highest in the control group compared to the poisoned group but was not statistically significant. Our critical assessment shows that using oxidative-stress-related parameters to evaluate the severity of CO poisoning, the outcome, and treatment options is challenging.

Carboxyhemoglobin as biomarker of late-onset sepsis in preterm infants.

Carboxyhemoglobin (COHb) is considered a biomarker of oxidative stress and previous studies reported an increase in COHb levels in preterm infants who develop late-onset sepsis (LOS). Our aim was to assess the correlation between COHb levels and the risk for LOS development. We retrospectively studied 100 preterm infants, 50 in the LOS and 50 in the no LOS group. COHb levels were measured on the day of diagnosis of the first episode of LOS, 3, 2, and 1 days before and 1 and 4 days after the onset of LOS. Logistic regression analysis showed that a higher level of COHb 2 days before the diagnosis of LOS increases the risk for LOS development (OR 12.150, 95% Cl 1.311-12.605; P = 0.028). A COHb level of 1.55% measured 2 days before the diagnosis of LOS is the best predictive threshold for LOS with a sensitivity of 70% and a specificity of 70%.    Conclusion: Increased levels of COHb may predict the diagnosis of LOS in very preterm infants with a good accuracy. If further studies confirm our findings, this easy-to-measure biomarker could provide neonatologists with another tool for monitoring and early diagnosis of sepsis in high-risk patients. What is Known: • Carboxyhemoglobin (COHb) is a biomarker of oxidative stress. • Previous studies reported an increase in COHb levels in preterm infants who develop late-onset sepsis (LOS). What is New: • COHb levels increased two days before the diagnosis of LOS and this increase was associated with the risk for developing LOS. • ROC curve analysis for COHb measured two days before the diagnosis of LOS showed that 1.55% is the best predictive threshold for LOS with a sensitivity of 70% and a specificity of 70%.

Thoracic cavity fluid as an alternative specimen for carboxyhaemoglobin measurement in post-mortem toxicology.

Post-mortem blood is most frequently used for the measurement of carboxyhaemoglobin (COHb) in post-mortem forensic cases, when investigating suspected inhalation of carbon monoxide (CO). However, in many post-mortem cases (especially severe burns and charring deaths), adequate blood specimens are not always available for toxicological analyses. Here, the availability of an alternative specimen for COHb analysis is required. This study investigated the suitability of thoracic cavity fluid (TCF) as an alternative specimen for the measurement of COHb. TCF and comparative blood samples from fifteen potential CO toxicity cases were collected into green-top tubes (containing lithium heparin) and analysed immediately after collection using a validated method on the ABL825 FLEX Radiometer CO-oximeter. Pearson's correlation coefficient indicated a strong positive relationship between the two specimens (r = 0.975, n = 10, p < 0.001). A statistical agreement between COHb concentrations from blood and TCF was demonstrated using the Bland-Altman plot, with a slight bias of 1.54 % when blood was taken as the standard. This study found that TCF would be a suitable alternative to blood for the measurement of COHb using the ABL825 FLEX blood gas analyser.