Balance of the prooxidant and antioxidant system is associated with mortality in critically ill patients

Abstract

It is well known that oxidative stress causes certain diseases and organ damage. However, roles of oxidative stress in the acute phase of critical patients remain to be elucidated. This study aimed to investigate the balance of oxidative and antioxidative system and to clarify the association between oxidative stress and mortality in critically ill patients. This cohort study enrolled 247 patients transported to our emergency department by ambulance. Blood was drawn on hospital arrival, and serum derivatives of reactive oxidant metabolites (dROMs, oxidative index) and biological antioxidant potential (BAP, antioxidative index) were measured. Modified ratio (MR) is also calculated as BAP/dROMs/7.51. There were 197 survivors and 50 non-survivors. In the non-survivors, dROMs were significantly lower (274 vs 311, p<0.01), BAP was significantly higher (2,853 vs 2,138, p<0.01), and MR was significantly higher (1.51 vs 0.92, p<0.01) compared to those in the survivors. The AUC of MR was similar to that for the APACHE II score. Contrary to our expectations, higher BAP and lower dROMs were observed on admission in non-survivors. This may suggest that the antioxidative system is more dominant in the acute phase of severe insults and that the balance toward a higher antioxidative system is associated with mortality.

Keywords: biological antioxidant potential; critically ill patients; modified ratio; mortality; oxidative stress.

Fig. 1.

Relationship between derivatives of reactive oxidant metabolites (dROMs) and biological antioxidant potential (BAP). Each circle indicates a survivor, and a cross indicates a non-survivor. Non-survivors tended to have lower dROMs and higher BAP compared to survivors.

Fig. 2.

Comparison of oxidative stress parameters between survivors, nonsurvivors, and healthy volunteers with box plots, histograms, and median [interquartile range (IQR)]. The horizontal line shows median of all patients. (A) d-ROMs, derivatives of reactive oxidant metabolites, (B) BAP, biological antioxidant potential, and (C) modified ratio. P values with * are indicated when the Steel-Dwass multiple comparison test showed significance.

Fig. 3.

Stepwise changes in mortality according to quintile divisions of oxidative stress parameters. (A) d-ROMs, derivatives of reactive oxidant metabolites, (B) BAP, biological antioxidant potential, and (C) MR, modified ratio. Percentage on each bar indicates mortality of each group. Trends were evaluated with the Cochrane-Armitage test.

Fig. 4.

Receiver-operating characteristic (ROC) analyses for mortality with the area under the curve (AUC) of each parameter. APACHE, Acute Physiology and Chronic Health Evaluation; BAP, biological antioxidant potential; dROMs, derivatives of reactive oxidant metabolites.