Increased heme catabolism in critically ill patients: correlation among exhaled carbon monoxide, arterial carboxyhemoglobin, and serum bilirubin IXα concentrations

Abstract

It has been reported that exhaled carbon monoxide (CO) concentrations and arterial carboxyhemoglobin (CO-Hb) concentration in blood may be increased in critically ill patients. However, there was no study that examined correlation among amount of CO in exhaled air, CO-Hb concentrations in erythrocytes, and bilirubin IXalpha (BR) in serum, i.e., the three major indexes of heme catabolism, within the same subject. Here, we examined CO concentrations in exhaled air, CO-Hb concentrations in arterial blood, and BR levels in serum in 29 critically ill patients. Measurements of exhaled CO, arterial CO-Hb, and serum total BR have been done in the intensive care unit. As control, exhaled CO concentration was also measured in eight healthy volunteers. A median exhaled CO concentration was significantly higher in critically ill patients compared with control. There was significant correlation between CO and CO-Hb and CO and total BR level. We also found CO concentrations correlated with indirect BR but not direct BR. Multivariate linear regression analysis for amount of exhaled CO concentrations also showed significant correlation with CO-Hb and total BR, despite the fact that respiratory variables of study subjects were markedly heterogeneous. We found no correlation among exhaled CO, patients' severity, and degree of inflammation, but we found a strong trend of a higher exhaled CO concentration in survivors than in nonsurvivors. These findings suggest there is an increased heme breakdown in critically ill patients and that exhaled CO concentration, arterial CO-Hb, and serum total BR concentrations may be useful markers in critically ill conditions.

Heme breakdown and ischemia/reperfusion injury in grafted liver during living donor liver transplantation

“…This increase in exhaled CO levels positively correlated with HO-1 gene expression levels in the grafted liver. Previously, we reported that exhaled CO levels significantly increased in critically ill patients in intensive care units and LDLT recipients after reperfusion (14,19). In this study, we again found an increase in post-reperfusion exhaled CO levels.…”

Increased exhaled carbon monoxide concentration during living donor liver transplantation

“…Previous studies reported that there was an increase in ExCO-C in inflammatory airway diseases, such as asthma, chronic obstructive pulmonary disease and cystic fibrosis (26)(27)(28). It has also been reported that ExCO-C was increased in systemic inflammatory diseases such as sepsis and critical illness (15,(29)(30)(31). Our findings in this study have additionally shown that I/R during LDLT led to an increase in ExCO-C, and indicate that I/R in LDLT is a significant oxidative stress on the grafted liver.…”

“…ExCO-C was measured using a newly developed CO analyzer (Carbolyzer™ mBA-2000, Taiyo Instruments, Inc., Osaka, Japan) as described previously (15). This instrument is equipped with a gas sensor based on the controlled potential electrolysis method (23) with sensitivity to 0.1 ppm of CO and capability of continuous side-stream sampling.…”

“…CO synthesized through the HO reaction diffuses out of cells, enters the bloodstream to form carboxyhemoglobin (CO-Hb) and is transported to the lung where it is excreted in ambient air (14). We previously demonstrated that the exhaled carbon monoxide concentration (ExCO-C) is increased in critically ill patients with systemic inflammation, via increased heme breakdown (15), and it is suggested that ExCO-C may reflect the degree of oxidative tissue injuries in the affected organ. We thus hypothesized that ExCO-C might also increase during LDLT and reflect the severity of tissue injury of the graft due to I/R.…”

Heme Proteins, Heme Oxygenase-1 and Oxidative Stress

“…Taken together, they concluded that the increased CO concentration in exhaled air in critically ill patients suggests an induction of inducible HO-1 and might reflect the severity of illness. Since CO is one of the metabolites of heme catabolism, we also examined CO concentrations in exhaled air, carboxyhemoglobin concentrations in arterial blood, and serum levels of bilirubin, another metabolite of heme breakdown, in 29 critically ill patients with signs of systemic inflammation who were all being mechanically ventilated (Morimatsu et al, 2006). Exhaled CO concentrations were also measured in eight healthy volunteers as controls.…”