The expired breath carbon delta value is a marker for the onset of sepsis in a swine model

Abstract

Approximately 750 000 people develop sepsis each year with more than 215 000 deaths. Earlier diagnosis and treatment of sepsis are critical to improving the outcome. The exhaled breath delta value (i.e.¹³CO₂/¹²CO₂ ratio, or BDV) is a biomarker for the acute phase response in sepsis models. The objective of this study was to define the temporal relationship between changes in the BDV, physiological and blood markers of sepsis in a porcine cecal ligation and puncture (CLP) model of sepsis. CLP led to a significant decrease in BDV in animals with stable mean arterial pressure during the course of the study, while the BDV of control animals was similar to that in animals that rapidly progressed into septic shock. The BDV indicated the onset of sepsis with a mean time of 3.54 hours (SEM 0.96) while physiological parameters detected the onset of sepsis in 11.11 hours (SEM 0.94) (p < 0.001). Biologic protein markers of inflammation (cytokines, including interleukin (IL)-1β, IL-4, IL-12, granulocyte/macrophage colony stimulating factor, interferon-gamma, and transforming growth factor-beta) did not change significantly during the experiment. Tumor necrosis factor-alpha was present at the baseline, at 2 hours in the control and CLP group with falling blood pressure, and at 8 hours in the control group. IL-6 was present at the baseline in all groups and spiked in the CLP animals with stable mean arterial pressure by 15 hours. The C-reactive protein was elevated in CLP and control animals by 8 hours (p < 0.05). Procalcitonin was present pre-surgery and increased above the baseline by 8 in CLP animals. These data show that the breath delta value is a leading indicator of sepsis in a porcine CLP model when compared to other physiological parameters.