Carboxyhemoglobin in pediatric sepsis and the systemic inflammatory response syndrome

Objective: Heme oxygenase-1 (HO-1) is an inducible enzyme that degrades heme to the biologically active products iron, carbon monoxide (which binds hemoglobin to give carboxyhemoglobin (COHb), and bilirubin. As mediators of inflammation induce HO-1 in vitro and in vivo, this enzyme may play a significant role in sepsis and the systemic inflammatory response syndrome (SIRS). If so, elevation of the indirect products of HO-1 activity, COHb and bilirubin, would be expected in patients during inflammatory stress states (sepsis/SIRS). The objective of this study was to determine whether these products might serve as diagnostic and/or prognostic markers of inflammatory stress. Design, setting, and subjects: A retrospective review of all patients admitted over a 36 month period to the intensive care unit (ICU) of a tertiary care pediatric oncology hospital was conducted. Abstracted data included initial COHb and bilirubin values, demographics, ventilatory support, medications, blood culture results, and mortality. Patients were divided into two groups, those with SIRS and those without, using the American College of Chest Physicians/Society of Critical Care Medicine (ACCP/ SCCM) consensus criteria. Within the SIRS group, a subgroup of patients with sepsis was identified. Measurements and main results: 190 patients admitted to the ICU were studied. Patients with SIRS (n=158) had higher mean initial COHb (1.4±0.06% vs. 1.0±0.09%, p = 0.002) and bilirubin levels (1.8 ± 0.3 mg/dl vs. 0.9 ± 0.2 mg/dl, p = 0.002) than patients without SIRS (n=32). Non-survivors had higher mean initial COHb and bilirubin levels than survivors (1.5 ± 0.11% vs. 1.2±0.06%, p = 0.044, and 3.1 ± 0.7 mg/ dl vs. 1.1 ± 0.1 mg/dl, p = 0.007, respectively). Elevated initial COHb (> 1.5%) and bilirubin (> 1.4 g/dl) levels were associated with mortality (Unadjusted OR = 2.2, 95% CI (1.1, 4.3), p = 0.024, and unadjusted OR = 5.1, 95% CI (2.5,10.6), p<0.001, respectively). Conclusions: Mean initial COHb and bilirubin levels were significantly higher in critically ill children with SIRS compared to critically ill children without SIRS in this patient population. This suggests that products of HO-1 activity may be early diagnostic markers for inflammatory stress. Higher initial values of both products were associated with mortality suggesting that products of HO-1 activity may serve as prognostic markers.