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.

Two similar carbon monoxide poisoning cases with different outcomes: evidence from longitudinal fMRI.

Prognosis after carbon monoxide (CO) poisoning is difficult to assess using structural images. Functional connectivity provided by functional magnetic resonance imaging (fMRI) may explain the mechanism of differential prognosis. We report here two cases of carbon monoxide poisoning with simultaneous coma. They were nearly normal on days 7-8, but diagnosed with delayed neurological sequelae (DNS) with cognitive and motor impairments on days 22-29. Similar Methylprednisolone pulse therapy and hyperbaric oxygen therapy were given to them. The movement disorder of case 1 improved slightly during the recovery stage, while the movement disorder of case 2 worsened significantly. In case 1, the function of supplementary motor area decreased first and then increased, and the function of pallidum increased first and then decreased. Case 2 showed a reduction in the supplementary motor area and small changes in the pallidum after DNS, but both were reduced during recovery stage. The cognitive ability of case 1 remained poor, while that of case 2 improved during the recovery stage. FMRI showed damage to the right and bilateral hippocampus in case 1 and partial damage to the left hippocampus in case 2. Taken together, fMRI can be a useful method to study functional connectivity abnormalities corresponding to different prognoses.

Risk of acute kidney injury among patients with carbon monoxide poisoning.

ABSTRACT: There is a lack of evidence supporting the association between carbon monoxide (CO) poisoning and acute kidney injury (AKI). Hence, the present study aimed to evaluate the association between CO poisoning and AKI.From 2000 to 2011, we identified patients diagnosed with CO poisoning from the inpatient claims data. Patients aged below 20 years, who had a history of chronic kidney disease or end-stage renal disease before the index date and had incomplete medical information were excluded. Control patients without CO poisoning were randomly selected from all National Health Insurance beneficiaries, and the same exclusion criteria were used. The control group was frequency matched to patients with CO poisoning based on age, sex, and year of CO poisoning diagnosis. Cox proportional hazards regression analyses were conducted to assess the effects of CO poisoning on the risk of AKI. The hazard ratios and 95% confidence interval (CI) were calculated in the models.Compared with the control cohort, patients with severe CO poisoning were 3.77 times more likely to develop AKI (95% CI = 2.20-6.46), followed by those with less severe CO poisoning (adjusted hazard ratio = 2.21, 95% CI = 1.61-3.03).The findings of this nationwide study suggest an increased risk of AKI in patients with CO poisoning.

Effect of Hyperbaric Oxygen Therapy Initiation Time in Acute Carbon Monoxide Poisoning.

OBJECTIVES: Hyperbaric oxygen therapy (HBO2) is recommended for symptomatic patients within 24-hour postcarbon monoxide poisoning. Previous studies have reported significantly better outcomes with treatment administered within 6 hours after carbon monoxide poisoning. Thus, we aimed to compare the neurocognitive outcomes according to HBO2 delay intervals. DESIGN: Retrospective analysis of data from our prospectively collected carbon monoxide poisoning registry. SETTING: A single academic medical center in Wonju, Republic of Korea. PATIENTS: We analyzed the data of 706 patients older than 16 years treated with HBO2 with propensity score matching. Based on carbon monoxide exposure-to-HBO2 delay intervals, we classified patients into the early (control, less than or equal to 6 hr) and late (case, 6-24 hr) groups. The late group was further divided into Case-1 (6-12 hr) and Case-2 (12-24 hr) groups. We also compared mild (nonintubated) and severe (intubated) groups. INTERVENTIONS: HBO2. MEASUREMENTS AND MAIN RESULTS: After propensity score matching, Global Deterioration Scale scores at 6 months postcarbon monoxide exposure showed significantly fewer poor outcome patients in the early than in the late group (p = 0.027). The early group had significantly fewer patients with poor outcomes than the Case-2 group (p = 0.035) at 1 month and than the Case-1 (p = 0.033) and Case-2 (p = 0.004) groups at 6 months. There were significantly more patients with poor prognoses at 6 months as treatment interval increased (p = 0.008). In the mild cohort, the early group had significantly fewer patients with poor 6-month outcomes than the late group (p = 0.033). CONCLUSIONS: Patients who received HBO2 within 6 hours of carbon monoxide exposure had a better 6-month neurocognitive prognosis than those treated within 6-24 hours. An increase in the interval to treatment led to an increase in poor outcomes.

Carbon monoxide-triggered health effects: the important role of the inflammasome and its possible crosstalk with autophagy and exosomes.

Carbon monoxide (CO) has long been known as a "silent killer" because of its ability to bind hemoglobin (Hb), leading to reduced oxygen carrying capacity of Hb, which is the main cause of CO poisoning (COP) in humans. Emerging studies suggest that mitochondria is a key target of CO action that can impact key biological processes, including apoptosis, cellular proliferation, inflammation, and autophagy. Despite its toxicity at high concentrations, CO also exhibits cyto- and tissue-protective effects at low concentrations in animal models of organ injury and disease. Specifically, CO modulates the production of pro- or anti-inflammatory cytokines and mediators by regulating the NLRP3 inflammasome. Given that human diseases are strongly associated with inflammation, a deep understanding of the exact mechanism is helpful for treatment. Autophagic factors and inflammasomes interact in various situations, including inflammatory disease, and exosomes might function as the bridge between the inflammasome and autophagy activation. Thus, the interplay among autophagy, mitochondrial dysfunction, exosomes, and the inflammasome may play pivotal roles in the health effects of CO. In this review, we summarize the latest research on the beneficial and toxic effects of CO and their underlying mechanisms, focusing on the important role of the inflammasome and its possible crosstalk with autophagy and exosomes. This knowledge may lead to the development of new therapies for inflammation-related diseases and is essential for the development of new therapeutic strategies and biomarkers of COP.

Alterations in cerebral and cardiac mitochondrial function in a porcine model of acute carbon monoxide poisoning.

OBJECTIVES: The purpose of this study is the development of a porcine model of carbon monoxide (CO) poisoning to investigate alterations in brain and heart mitochondrial function. DESIGN: Two group large animal model of CO poisoning. SETTING: Laboratory. SUBJECTS: Ten swine were divided into two groups: Control (n = 4) and CO (n = 6). INTERVENTIONS: Administration of a low dose of CO at 200 ppm to the CO group over 90 min followed by 30 min of re-oxygenation at room air. The Control group received room air for 120 min. MEASUREMENTS: Non-invasive optical monitoring was used to measure cerebral blood flow and oxygenation. Cerebral microdialysis was performed to obtain semi real time measurements of cerebral metabolic status. At the end of the exposure, both fresh brain (cortical and hippocampal tissue) and heart (apical tissue) were immediately harvested to measure mitochondrial respiration and reactive oxygen species (ROS) generation and blood was collected to assess plasma cytokine concentrations. MAIN RESULTS: Animals in the CO group showed significantly decreased Complex IV-linked mitochondrial respiration in hippocampal and apical heart tissue but not cortical tissue. There also was a significant increase in mitochondrial ROS generation across all measured tissue types. The CO group showed a significantly higher cerebral lactate-to-pyruvate ratio. Both IL-8 and TNFα were significantly increased in the CO group compared with the Control group obtained from plasma. While not significant there was a trend to an increase in optically measured cerebral blood flow and hemoglobin concentration in the CO group. CONCLUSIONS: Low-dose CO poisoning is associated with early mitochondrial disruption prior to an observable phenotype highlighting the important role of mitochondrial function in the pathology of CO poisoning. This may represent an important intervenable pathway for therapy and intervention.

Evaluation of the Cardioprotective Effect of Granulocyte Colony Stimulating Factor in Patients with Carbon Monoxide Poisoning.

BACKGROUND: Carbon monoxide (CO), which is well known as silent killer, has many toxic effects on organs with high rate of metabolism such as heart and brain. CO-induced cardiotoxicity resulted in a wide range of disabilities including electrocardiogram (ECG) abnormalities, elevation in level of cardiac enzymes, arrhythmias, impairment of left ventricular and myocardial infarction (MI). Cardio-protective effects of Granulocyte colony-stimulating factor (G-CSF) on infarcted heart was proved previously in various reports. OBJECTIVE: In this study, possible effect of G-CSF on cardiac function of patients with moderate to severe acute CO poisoning was investigated. METHODS: Cardioprotective effects of G-CSF in CO-poisoned patients was evaluated through ECG, Holter monitoring, echocardiography, and biochemical studies. Continuous intravenous infusion of G-CSF (90 µg/kg) and normal saline were administered respectively to treatment and placebo groups. RESULTS: The results demonstrated that in moderate to severe CO poisoning, myocardial injury is common. ECG changes (e.g., ST-segment and T-wave changes, QTC), cardiac arrhythmias (e.g., heart blocks and ventricular arrhythmias), serum level of Troponin I, left ventricular ejection fraction were determined after G-CSF administration. Frequencies of ST depression, inversion or flatting of T wave and QTC in ECG were significantly reduced after G-CSF treatment. In addition, incidence of cardiac arrhythmias due to CO poisoning were reduced after G-CSF treatment. However, G-CSF did not exert protective effects on TPI level and function of left ventricular in CO-poisoned patients. CONCLUSION: GCSF could probably reduce CO-induced cardiac ischemia in patients with acute CO poisoning. CLINICAL TRIAL REGISTRATION: The trial protocol was registered in the Iranian Registry of Clinical Trials (http://www.irct.ir) registry (Irct ID: IRCT201607232083N7).

Carbon monoxide increases utero-placental angiogenesis without impacting pregnancy specific adaptations in mice.

BACKGROUND: Cigarette smokers have a reduced risk of developing preeclampsia, possibly attributed to an increase in carbon monoxide (CO) levels. Carbon monoxide is a gasotransmitter that has been implicated in maintaining vascular tone, increasing angiogenesis, and reducing inflammation and apoptosis at physiological concentrations. Moderately increasing CO concentrations may have therapeutic potential to prevent or treat preeclampsia; however, the effects of CO on pregnancy are under studied. Our objective was to investigate the effect of CO on major angiogenic and inflammatory markers in pregnancy, and to evaluate the effect of CO on indicators of placental health. FINDINGS: Pregnant CD-1 mice were constantly exposed to either ambient air or 250 ppm CO from conception until gestation day (GD)10.5 or GD16.5. Using a qRT-PCR array, we identified that CO increased expression of major angiogenic genes at the implantation site on GD10.5, but not GD16.5. Pro-inflammatory cytokines in the plasma and tissue lysates from implantation sites in treated mice were not significantly different compared to controls. Additionally, CO did not alter the implantation site phenotype, in terms of proliferative capacity, invasiveness of trophoblasts, or abundance of uterine natural killer cells. CONCLUSIONS: This study suggests that CO exposure is pro-angiogenic at the maternal-fetal interface, and is not associated with demonstrable concerns during murine pregnancy. Future studies are required to validate safety and efficacy of CO as a potential therapeutic for vascular insufficiency diseases such as preeclampsia and intrauterine growth restriction.

Altered regional homogeneity in delayed encephalopathy after carbon monoxide poisoning: A resting-state fMRI study.

OBJECTIVE: To investigate alternations in spontaneous brain activities reflected by regional homogeneity (ReHo) in patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP) using resting-state functional magnetic resonance imaging (rs-fMRI). METHODS: Twenty-one patients with DEACMP and 21 age, sex and education matched healthy controls (HCs) received rs-fMRI scanning and clinical assessment. We used the ReHo method to analyze the interregional synchronized activity of all participants. Two sample t-tests were performed to compare the ReHo maps between the two groups. Pearson correlation analysis was then used to assess the correlations between clinical measures and abnormal ReHo in DEACMP patients. RESULTS: Compared with HCs, DEACMP patients showed significantly decreased ReHo in bilateral cerebellum posterior lobe, pons, bilateral basal ganglia, while increased in the posterior cingulate, calcarine, bilateral occipital lobe(GRF correction, voxel P value <0.001, cluster P value <0.05). Negative correlation was found between Mini-mental State Examination (MMSE) scores and the ReHo values of posterior cingulate gyrus (r = -0.672, p < 0.05) in the DEACMP group, while positively related to the time from CO poisoning to MRI scan (r = 0.428, p < 0.05). CONCLUSION: Patients with DEACMP exhibited altered ReHo in the multiple functional brain regions, which provide evidence for local brain dysfunctions and may help to understand the neuropathologic mechanism for the disease.

Longitudinal gray matter changes of the pain matrix in patients with carbon monoxide intoxication: A voxel-based morphometry study.

PURPOSE: Carbon monoxide (CO) intoxication causes gray matter (GM) changes and headache symptom in patients with CO intoxication, but the headache-associated GM changes are not well understood. The purpose of this study was to perform a voxel-based morphometry (VBM) analysis to investigate longitudinal GM changes of brain pain matrix in patients with CO intoxication. METHODS: This prospective study enrolled 24 patients with CO intoxication and 20 healthy controls. Whole brain high-resolution T1-weighted images were acquired in both groups and were repeated in patients at 1 week, and 1, 3, and 9 months after CO exposure. VBM was performed to detect global GM changes in patients with CO intoxication, and the automated anatomical labeling template was utilized to estimate the distribution of significant GM clusters in the brain. RESULTS: GM volumes were significantly decreased mainly in the frontal and occipital lobes, including several pain-matrix regions 1 week after CO intoxication. The regions with significant GM changes further involved the central GM structures and the periaqueductal gray (pain-modulating center) at 1 and 3 months after CO intoxication, but the alterations were partially normalized in the frontal lobe and cerebellum 9 months after CO intoxication. Significant negative correlations were revealed between GM volume and duration of coma in the pain matrix regions. Moreover, five patients exhibited delayed neuropsychiatric sequelae (DNS) and had greater GM volume changes than non-DNS patients. CONCLUSION: VBM analysis is helpful to understand the longitudinal GM changes of the pain matrix in patients with CO intoxication.

Blood carboxyhemoglobin elimination curve, half-lifetime, and arterial-venous differences in acute phase of carbon monoxide poisoning in ovine smoke inhalation injury model.

Smoke inhalation injury (SII) affects more than 50,000 people annually causing carbon monoxide (CO) poisoning. Although the increased blood level of carboxyhemoglobin (CO-Hb) is frequently used to confirm the diagnosis of SII, knowledge of its elimination in the acute phase is still limited. The aim of this study is to determine CO-Hb elimination rates and their differences in arterial (aCO-Hb) and mixed-venous (vCO-Hb) blood following severe SII in a clinically relevant ovine model. Forty-three chronically instrumented female sheep were subjected to SII (12 breaths, 4 sets) through tracheostomy tube under anesthesia and analgesia. After the SII, sheep were awakened and placed on a mechanical ventilator (FiO2 = 1.0, tidal volume 12 mL/kg, and PEEP = 5cmH2O) and monitored. Arterial and mixed-venous blood samples were withdrawn simultaneously for blood gas analysis at various time points to determine CO-HB half-lifetime and an elimination curve. The mean of highest aCO-Hb level during SII was 70.8 ± 13.9%. The aCO-Hb elimination curve showed an approximated exponential decay during the first 60 min. Per mixed linear regression model analysis, aCO-Hb significantly (p < 0.001) declined (4.3%/minute) with a decay constant lambda of 0.044. With this lambda, mean lifetime and half-lifetime of aCO-Hb were 22.7 and 15.7 min, respectively. The aCO-Hb was significantly lower compared to vCO-Hb at all-time points (0-180 min). To our knowledge, this is the first report describing CO-Hb elimination curve in the acute phase after severe SII in the clinically relevant ovine model. Our data shows that CO-Hb is decreasing in linear manner with supportive mechanical ventilation (0-60 min). The results may help to understand CO-Hb elimination curve in the acute phase and improvement of pre-hospital and initial clinical care in patients with CO poisoning.

Demographic characteristics and delayed neurological sequelae risk factors in carbon monoxide poisoning.

AIM: Carbon monoxide (CO) is a colorless, odorless gas and tasteless. CO poisoning (COP) is one of the most frequently encountered inhalation poisonings. The most common cause of morbidity in COP is delayed neurological sequelae (DNS). DNS is the occurrence of neuropsychiatric findings within 2-240 days after discharge of patients with COP and there are no definitive diagnostic criteria. The aim of our study is; to determine the risk factors and incidence of DNS. METHOD: Our study is a retrospective, observational study. Patients with the diagnosis of COP in the emergency department between 2015 and 2016 were included in the study. Patients age, gender, findings in the initial physical examination (PE) and neurological examination (NE), blood carboxyhemoglobin (COHb) level, relation between hyperbaric oxygen (HBO) treatment and DNS were assessed. RESULTS: Total of 72 patients were included in the study. Mean age was 33.43 ±â€¯20.89. It was determined that pathological findings in the initial NE are a significant predictive factor for DNS (Odds ratio 18.600, p:0.004). Significant relation between NE and HBO treatment was present (p:00.1). There was no statistically significant relationship between initial COHb level and receiving HBO treatment (p:0.9). Median COHb level of patients with DNS was 30 (min:10, max: 43), median COHb level of patients without DNS was 25 (min:10, max:44) and there was no statistically significant relationship between the two groups according to COHb levels (p:0.7). CONCLUSION: Pathological findings in the initial neurological examination had a predictive value for delayed neurological sequelae in patients with carbon monoxide poisoning.

Unreliable Early Neuroprognostication After Severe Carbon Monoxide Poisoning Is Likely Due to Cytopathic Hypoxia: A Case Report and Discussion.

A 17-year-old girl was found unconscious in a running vehicle. She developed very severe acute respiratory distress syndrome (which was treated with rescue high-frequency oscillation), hemodynamic instability, acute kidney injury, rhabdomyolysis, and remained comatose with a Glasgow Coma Scale score of 3 and gasping respirations for 67 hours (when the Glasgow Coma Scale score improved to 6, with tachypnea to Paco 2 28 and pH 7.5). By 92 hours, she was obeying commands, and she was extubated at 96 hours, shortly after which she was conversing with family and texting on her phone. A magnetic resonance imaging (MRI) scan 6 days after being found showed subacute infarctions affecting the medial aspect of the globus pallidus bilaterally as well as a small cortical/subcortical infarction in the right parietal lobe. At a 7-week follow-up, she had no delayed-onset signs of brain injury. This case demonstrated that neurologic prognostication after carbon monoxide poisoning may be unreliable for more than 72 hours after injury. We discuss that it is possible that the mitochondrial dysfunction induced by carbon monoxide was responsible for a functional coma without irreversible brain injury, similar to the mechanism of cytopathic hypoxia in multiple-organ dysfunction that allows some other organ recovery without necrosis in survivors.

Myocardial Repolarization Parameters and Neutrophil-to-Lymphocyte Ratio are Associated with Cardiotoxicity in Carbon Monoxide Poisoning.

The present study aims to examine the clinical values of complete blood count (CBC) bioindicators and corrected QT (QTc), Tpeak - Tend interval (Tp-e), Tpeak dispersion (Tp disp), and Tp-e/QT ratio that are the parameters of myocardial repolarization (M-rep) for cardiotoxicity, which develops due to acute carbon monoxide (CO) intoxication in patients admitted to the emergency service. This retrospective, cross-sectional, observational, and single-center study was conducted between April and June 2019. Statistical analysis was performed using the SPSS 23.0 software. Data of 234 participants were analyzed. Of these, 54.9% (n = 129) were female. Neutrophil-to-lymphocyte ratio (NLR), QTc, Tp-e values were significantly high in the CO intoxication group (p < 0.001, p < 0.001, and p < 0.001, respectively), whereas Tp-e/QTc ratio was significantly lower in the CO intoxication group than that in the control group (p < 0.001). NLR, Tp-e, Tp disp values were significantly high in the myocardial injury (M-inj) group (p < 0.001, p = 0.003, and p = 0.018, respectively). Furthermore, Tp-e/QTc ratio was significantly low in the M-inj group (p = 0.002). M-rep parameters and NLR are associated with CO intoxication and the development of M-inj. Moreover, these bioindicators and can provide clinicians an early indication of M-inj.

A case report on the acute and late complications associated with carbon monoxide poisoning: Acute kidney injury, rhabdomyolysis, and delayed leukoencephalopathy.

RATIONALE: Acute kidney injury (AKI), rhabdomyolysis, and delayed leukoencephalopathy after carbon monoxide (CO) poisoning are very rare. We report a case presenting with AKI, rhabdomyolysis, and delayed leukoencephalopathy after CO poisoning. PATIENT CONCERNS: The patient was admitted to our emergency department due to loss of consciousness after CO exposure during a suicide attempt. DIAGNOSES: Laboratory findings revealed elevated carboxyhemoglobin, serum creatinine, and serum muscle enzyme levels. Initially, this patient was diagnosed with AKI and rhabdomyolysis due to CO poisoning. A month after the CO poisoning, she showed neuropsychiatric symptoms. Brain magnetic resonance imaging showed white-matter hyperintensity on the T2 flair image. Therefore, she was diagnosed with delayed leukoencephalopathy after CO poisoning. INTERVENTIONS: At the same time as diagnosis of AKI and rhabdomyolysis, the normobaric oxygen and hydration therapies were performed. A month later, rehabilitation was started due to delayed leukoencephalopathy. OUTCOMES: Her renal function and muscle enzyme levels were completely restored with alert mental status. She could walk with the aid of a walker at last visit. LESSONS: This case shows that we should consider about rare acute and late complications such as AKI, rhabdomyolysis, and delayed leukoencephalopathy after CO poisoning.