Use of Carboxyhemoglobin as an Early Sign of Oxygenator Dysfunction in Patients Supported by Extracorporeal Membrane Oxygenation.

Introduction: Plasma free hemoglobin is the gold standard for monitoring hemolysis in extracorporeal membrane oxygenation (ECMO) but its routine use has some limitations. Carboxyhemoglobin (HbCO) is also a marker of intravascular hemolysis. We aimed to investigate HbCO as a marker of both hemolysis and oxygenator dysfunction in patients supported by ECMO. Methods: Retrospective analysis of patients on ECMO in an adult ICU in a tertiary hospital. HbCO was recorded every 6 h in the 48 h before and after oxygenator change in adult patients on ECMO support with an oxygenator dysfunction and replacement. Results: The investigation of 27 oxygenators replacements in 19 patients demonstrated that HbCO values progressively increased over time and then significantly decreased after oxygenator change. Median oxygenator lifespan was 14 days [interquartile range (IQR) 8-21] and there was no correlation between HbCO and oxygenator lifespan [Spearman coefficient 0.23 (p = 0.23)]. HbCO values at oxygenator change [HbCO median 2.7 (IQR 2.5-3.5)] were significantly higher than the HbCO values 1 week before [HbCO median 2.07 (IQR 1.86-2.8)] (p value < 0.001). Conclusion: Our data highlight the potential role of HbCO as a novel marker for ECMO oxygenator dysfunction.

Can we detect in vivo hemolysis during extracorporeal membrane oxygenation support using endogenous carbon monoxide production?

Introduction: Extracorporeal membrane oxygenation (ECMO) has been widely used in patients with ARDS due to COVID-19. In vivo hemolysis (ivH) is one of its complications, characterised by peaks of plasma free hemoglobin (fHb). However, an increase in carboxyhemoglobin (COHb) has also been observed due to Hb metabolism by heme-oxygenase that releases carbon monoxide. The aim of this study is to evaluate the incidence of ivH events and their relation to COHb in COVID-19 patients undergoing ECMO. Method(s): Single-centre observational retrospective study that included 33 COVID-19 patients with ARDS who received VV-ECMO treatment in the ICU from March 2020 to September 2021. Daily analytical monitoring was carried out including arterial blood gas test with cooximetry and biochemical parameters, incorporating the estimation of fHb using quantitative hemolysis index (HI). Significant ivH was considered with fHb > 50 mg/dL after discarding in vitro hemolysis. Daily maximum values of HI and COHb were recorded and paired in order to evaluate their correlation by generalised linear model. Result(s): The total prevalence of patients having ivH in our cohort was 27.3%. Mortality during ECMO treatment in our study was 57.6%, higher within the group of patients with ivH events (77.8% vs 50%). A total of 777 daily maximum values of fHb from all the patients were obtained. Values of COHb were significantly higher during ivH episodes. Furthermore, positive significant correlation was obtained between daily analytical values of fHb and COHb (B coefficient 42.156;p = 0.042), as shown in Fig. 1. The cut-off value of COHb to be discriminative for hemolysis (fHb > 50 mg/dL) was 3.85% COHb (90.5% sensitivity and 83.3% specificity). Conclusion(s): Point-of-care carboxyhemoglobin is a cheap and widely available parameter that could be useful when detecting in vivo hemolysis during ECMO treatment.

Predictive markers related to local and systemic inflammation in severe COVID-19-associated ARDS: a prospective single-center analysis.

BACKGROUND: As the COVID-19 pandemic strains healthcare systems worldwide, finding predictive markers of severe courses remains urgent. Most research so far was limited to selective questions hindering general assumptions for short- and long-term outcome. METHODS: In this prospective single-center biomarker study, 47 blood- and 21 bronchoalveolar lavage (BAL) samples were collected from 47 COVID-19 intensive care unit (ICU) patients upon admission. Expression of inflammatory markers toll-like receptor 3 (TLR3), heme oxygenase-1 (HO-1), interleukin (IL)-6, IL-8, leukocyte counts, procalcitonin (PCT) and carboxyhemoglobin (CO-Hb) was compared to clinical course. Clinical assessment comprised acute local organ damage, acute systemic damage, mortality and outcome after 6 months. RESULTS: PCT correlated with acute systemic damage and was the best predictor for quality of life (QoL) after 6 months (r = - 0.4647, p = 0.0338). Systemic TLR3 negatively correlated with impaired lung function (ECMO/ECLS: r = - 0.3810, p = 0.0107) and neurological short- (RASS mean: r = 0.4474, p = 0.0023) and long-term outcome (mRS after 6 m: r = - 0.3184, p = 0.0352). Systemic IL-8 correlated with impaired lung function (ECMO/ECLS: r = 0.3784, p = 0.0161) and neurological involvement (RASS mean: r = - 0.5132, p = 0.0007). IL-6 in BAL correlated better to the clinical course than systemic IL-6. Using three multivariate regression models, we describe prediction models for local and systemic damage as well as QoL. CO-Hb mean and max were associated with higher mortality. CONCLUSIONS: Our predictive models using the combination of Charlson Comorbidity Index, sex, procalcitonin, systemic TLR3 expression and IL-6 and IL-8 in BAL were able to describe a broad range of clinically relevant outcomes in patients with severe COVID-19-associated ARDS. Using these models might proof useful in risk stratification and predicting disease course in the future. Trial registration The trial was registered with the German Clinical Trials Register (Trial-ID DRKS00021522, registered 22/04/2020).

The Trend of Arterial Carboxyhemoglobin in Non-smokers as a Prognostic Tool in Severe COVID-19 Patients: A Single-Centre Prospective Study.

Introduction  Carboxyhemoglobinemia is characterised by decreased oxygen delivery to tissues. In severe and critical coronavirus disease 2019 (COVID-19) illness with hypoxia, this can herald a grave and protracted course of illness. Patients with COVID-19 experience respiratory impairment, lowering the pace at which carbon monoxide (CO) is eliminated and raising the likelihood of carboxyhemoglobinemia. We set out to explore early arterial carboxyhemoglobin (COHb) and COVID-19 patient outcomes in non-smokers and its potential as a predictive tool for mortality. Methods  Forty-five patients, non-smokers with severe/critical severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring admission in a North Indian 1200-bedded tertiary care hospital, were recruited prospectively from October 2020 to March 2021. Arterial COHb% was evaluated with arterial blood gases using an analyser, which were taken at the time of admission and then every alternate day for the first 10 days. Carboxyhemoglobinemia was defined as COHb% more than 1%. The primary outcome was defined as the patient's hospital outcome (survivor/non-survivor). Results Of the total 45 subjects, 51.1% (n=23) survived. Patients developed carboxyhemoglobinemia with an incidence of 51% during the course of their hospital stay. The mean ± SD of COHb% on admission was 1.0 ± 0.58 and 1.03 ± 0.8 in non-survivors and survivors, respectively (p=0.870). Maximal individual values of 5.3% and 6.1% were seen in survivors and non-survivors, respectively. On serial COHb measurement, non-survivors had significantly higher COHb% on days 6 and 10. No co-relation of COHb% with inflammatory markers was noted. Conclusion  Arterial COHb levels in non-survivors were significantly higher than in survivors on days 6 and 10. Our study did not show a prognostic value of serial COHb measurement in patients with severe COVID-19. To establish COHb as a predictive marker in severely ill COVID-19 patients, additional research is required.

A curious method to commit suicide

Objective: The COVID-19 pandemic has generated an increase in anxiety-depressive disorders throughout society, with an evident impact on children and adolescents, further precipitated by limitations in social activities during confinement. The increase in home isolation with abuse of new technologies, often far from parental control, involves risky situations such as the case we present. Case report: A 19-year-old man diagnosed with major depressive disorder, with psychiatric admissions since July 2019 for overdose with suicidal intent was home treated with methylphenidate 40mg, mirtazapine 15mg and vortioxetine 10mg. In August, the patient was searching for information on the Internet about euthanasia and suicide without pain in different pages and Internet forums. He bought two products online (by Amazon) that seemed effective for this purpose: a kilogram packet of sodium nitrate and a bottle of antifreeze. Finally, he decided on the first option due to the risk of suffering after ingesting antifreeze. On August 26 (4:00 pm), he ate a tablespoon (80 mg) of sodium nitrate. He developed dyspnea and feeling overwhelmed so he decided to informed his family of what he had done and an ambulance was called. He was transferred to hospital and given oxygen. At 7:00 pm in the emergency department he was noted to have a greyish coloration (“hot dead” appearance) with poor respiratory mechanics, tachycardic, tachypneic, with signs of peri-arrest: blood pressure 96/50mmHg, heart rate 145 bpm, respiratory rate 30/min, oxygen saturations 70%. He also had uncoordinated movements, and could not obey orders. The patient was sedated for intubation and mechanical ventilation. An arterial blood gas analysis performed after intubation showed: pH 7.35, pO2 165mmHg, pCO2 24mmHg, base excess -10.4, bicarbonate 14.5 mEq/L, potassium 3.1 mmol/L, methemoglobin 83%, carboxyhemoglobin 1.4%, lactate 13.3mmol/L. Methylene blue 1% (75mg intravenously) and activated charcoal by nasogastric tube were administered (after intubation). Later, he was admitted to the intensive care unit (9:20 pm). Physicians from this unit decided to administrate hydroxocobalamin (5 g intravenously at 00.39 am). The patient was extubated and discharged from the intensive care unit 36 hours after his admission to the department of Internal Medicine, without clinical complications;later he was transferred to Psychiatry Department. Conclusion: The toxic mechanism of sodium nitrate is related to the generation of methemoglobin. This patient survived a potentially lethal methemoglobin level following intentional ingestion of sodium nitrate with prompt administration of an antidote.

Three cases of clinically significant inaccurate carboxyhemoglobin measurement.

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

Spectrum of hematological changes in COVID-19

Coronavirus disease 2019 (COVID-19) is caused by pathogenic and highly transmissible Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is a single stranded RNA virus. It rapidly emerged from an epidemic to a global pandemic form spreading in alarming levels. The pathogenesis involving spike protein which is present on the viral surface, plays a key role in host attachment and penetration. SARS-CoV-2 infection significantly affects respiratory system, but may involve other systems including haematopoietic system and homeostasis. Aim of the review article is to discuss spectrum of haematological changes in the blood counts, coagulation, peripheral blood and bone marrow in COVID-19 for complete understanding the disease process, the knowledge of which is helpful in early diagnosis and management of these patients. An extensive immune profiling of B and T cell population with analysis of spectrum of immune changes during the period of infection were also discussed. In COVID-19, changes in laboratory parameters and hematologic abnormalities have been reported and its association with early diagnosis, disease prognosis and severity has been repeatedly discussed in the literature. Changes in laboratory investigations help in risk stratification and early intervention. The most common laboratory finding in COVID-19 is lymphopenia. COVID-19 patients presented with coagulopathy is at high risk of morbidity and mortality. In severe COVID-19 patients, bone marrow aspirate shows histiocytic proliferation with hemophagocytosis. To understand the correlations between immune responses and severity of COVID-19, immune profiling of B and T cell population was compared with extensive clinical data. A deep understanding of the laboratory findings and haematological abnormalities associated with SARS-CoV-2 infection would help to raise disease suspicion in absence of Real time polymerase chain reaction or antibody results. Also the blood counts along with the morphological changes in peripheral blood would be helpful in prompt screening, diagnosis, prognosis and management of COVID-19 patients.

Endogenous Carboxyhemoglobin Level Variation in COVID-19 and Bacterial Sepsis: A Novel Approach?

BACKGROUND: The increased production of carbon monoxide (CO) in sepsis has been proven, but the blood level variations of carboxyhemoglobin (COHb) as a potential evolutionary parameter of COVID-19 and sepsis/septic shock have yet to be determined. This study aims to evaluate the serum level variation of COHb as a potential evolutionary parameter in COVID-19 critically ill patients and in bacterial sepsis. MATERIALS AND METHOD: A prospective and observational study was conducted on two groups of patients: the bacterial sepsis group (n = 52) and the COVID-19 group (n = 52). We followed paraclinical parameters on Day 1 (D1) and Day 5 (D5) of sepsis/ICU admission for COVID-19 patients. RESULTS: D1 of sepsis: statistically significant positive correlations between: COHb values and serum lactate (p = 0.024, r = 0.316), and total bilirubin (p = 0.01, r = 0.359). In D5 of sepsis: a statistically significant positive correlations between: COHb values and procalcitonin (PCT) (p = 0.038, r = 0.402), and total bilirubin (p = 0.023, r = 0.319). D1 of COVID-19 group: COHb levels were statistically significantly positively correlated with C-reactive protein CRP values (p = 0.003, r = 0.407) and with PCT values (p = 0.022, r = 0.324) and statistically significantly negatively correlated with serum lactate values (p = 0.038, r = -0.285). CONCLUSION: COHb variation could provide rapid information about the outcome of bacterial sepsis/septic shock, having the advantages of a favorable cost-effectiveness ratio, and availability as a point-of-care test.

Carboxyhemoglobinemia in Critically Ill Coronavirus Disease 2019 Patients.

Carboxyhemoglobinemia is a common but a serious disorder, defined as an increase in carboxyhemoglobin level. Unfortunately, there are few data on carboxyhemoglobinemia in coronavirus disease 2019 (COVID-19) patients. Therefore, our study aimed to evaluate the incidence and etiologies of carboxyhemoglobinemia in COVID-19 patients and determine any association between carboxyhemoglobinemia and novel coronavirus infection. A retrospective chart review was performed at an academic medical center for all inpatient COVID-19 cases with either single or serial carboxyhemoglobin (COHb) levels from March 2020 through August 2020.Our study demonstrates that carboxyhemoglobinemia in COVID-19 patients is due to sepsis, hemolysis, and cytokine storm, triggered by the novel coronavirus infection sequela and is not directly from the virulence of novel coronavirus. Given the coexisting illnesses in critically ill COVID-19 patients, it is impossible to establish if coronavirus virulence was the culprit of elevated COHb levels. Moreover, our study found a high incidence of carboxyhemoglobinemia in critically ill COVID-19 patients. The oxygen saturation measured by pulse oximetry can be inaccurate and unreliable; however, our study could not demonstrate any uniform results on the discrepancy between oxygen saturation measured by pulse oximetry and arterial blood gas. In this study, COHb levels were measured using a CO-oximeter. Therefore, we recommend monitoring the COHb level routinely in critically ill COVID-19 patients to allow more effective and prompt treatment.

Prediction of diagnosis and prognosis of COVID-19 disease by blood gas parameters using decision trees machine learning model: a retrospective observational study.

The coronavirus disease 2019 (COVID-19) epidemic went down in history as a pandemic caused by corona-viruses that emerged in 2019 and spread rapidly around the world. The different symptoms of COVID-19 made it difficult to understand which variables were more influential on the diagnosis, course and mortality of the disease. Machine learning models can accurately assess hidden patterns among risk factors by analyzing large-datasets to quickly predict diagnosis, prognosis and mortality of diseases. Because of this advantage, the use of machine learning models as decision support systems in health services is increasing. The aim of this study is to determine the diagnosis and prognosis of COVID-19 disease with blood-gas data using the Chi-squared Automatic Interaction Detector (CHAID) decision-tree-model, one of the machine learning methods, which is a subfield of artificial intelligence. This study was carried out on a total of 686 patients with COVID-19 (n = 343) and non-COVID-19 (n = 343) treated at Erzincan-Mengücek-Gazi-Training and Research-Hospital between April 1, 2020 and March 1, 2021. Arterial blood gas values of all patients were obtained from the hospital registry system. While the total-accuracyratio of the decision-tree-model was 65.0% in predicting the prognosis of the disease, it was 68.2% in the diagnosis of the disease. According to the results obtained, the low ionized-calcium value (< 1.10 mM) significantly predicted the need for intensive care of COVID-19 patients. At admission, low-carboxyhemoglobin (< 1.00%), high-pH (> 7.43), low-sodium (< 135.0 mM), hematocrit (< 40.0%), and methemoglobin (< 1.30%) values are important biomarkers in the diagnosis of COVID-19 and the results were promising. The findings in the study may aid in the early-diagnosis of the disease and the intensive-care treatment of patients who are severe. The study was approved by the Ministry of Health and Erzincan University Faculty of Medicine Clinical Research Ethics Committee.

The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review.

Following the outbreak of a novel coronavirus (SARS-CoV-2) associated with pneumonia in China (Corona Virus Disease 2019, COVID-19) at the end of 2019, the world is currently facing a global pandemic of infections with SARS-CoV-2 and cases of COVID-19. Since severely ill patients often show elevated methemoglobin (MetHb) and carboxyhemoglobin (COHb) concentrations in their blood as a marker of disease severity, we aimed to summarize the currently available published study results (case reports and cross-sectional studies) on MetHb and COHb concentrations in the blood of COVID-19 patients. To this end, a systematic literature research was performed. For the case of MetHb, seven publications were identified (five case reports and two cross-sectional studies), and for the case of COHb, three studies were found (two cross-sectional studies and one case report). The findings reported in the publications show that an increase in MetHb and COHb can happen in COVID-19 patients, especially in critically ill ones, and that MetHb and COHb can increase to dangerously high levels during the course of the disease in some patients. The medications given to the patient and the patient's glucose-6-phospate dehydrogenase (G6PD) status seem to be important factors determining the severity of the methemoglobinemia and carboxyhemoglobinemia. Therefore, G6PD status should be determined before medications such as hydroxychloroquine are administered. In conclusion, MetHb and COHb can be elevated in COVID-19 patients and should be checked routinely in order to provide adequate medical treatment as well as to avoid misinterpretation of fingertip pulse oximetry readings, which can be inaccurate and unreliable in case of elevated MetHb and COHb levels in the blood.

Role of methemoglobin and carboxyhemoglobin levels in predicting COVID-19 prognosis: an observational study.

World Health Organization has declared coronavirus disease-19 (COVID-19) as a pandemic. Although there are studies about this novel virus, our knowledge is still limited. There is limited information about its diagnosis, treatment and prognosis. We aimed to investigate the effect of methemoglobin and carboxyhemoglobin levels on the prognosis of COVID-19. In this observational study, patients who were diagnosed with COVID-19 during March 1-April 31, 2020 in a secondary-level state hospital in Turkey were included in the study. COVID-19 diagnosis was confirmed with reverse transcription polymerase chain reaction method, with nasal, oral or sputum specimens. During the period this study was performed, 3075 patients were tested for COVID-19 and 573 of them were hospitalized. Among the hospitalised patients, 23.2% (133) of them had a positive polymerase chain reaction result for COVID-19. A total of 125 patients, 66 (52.8%) males and 59 (47.2%) females, with an average age of 50.2 ± 19.8 years, were included in the study. The most common findings in chest radiogram were ground-glass areas and consolidations, while one-third of the patients had a normal chest radiogram. Computed thorax tomography was performed for 77.6% (97/125) of the patients. The 24.7% of computed tomographies (24/97) did not reveal any pathological findings, and the most common findings were ground-glass appearance and consolidation. Those who needed intensive care had statistically significantly lower platelet count (P = 0.011) and higher lactate dehydrogenase levels (P < 0.001). No statistically significant difference was found in carboxyhemoglobin (P = 0.395) and methemoglobin (P = 1.000) levels. We found that carboxyhemoglobin and methemoglobin levels had no effect on COVID-19 prognosis, but low platelet level played a role in predicting COVID-19 prognosis. This study was approved by the Ethical Committee of Harran University Faculty of Medicine on May 11, 2020 with approval No. 09.