Reduction of oxidative stress a key for enhanced postoperative recovery with fewer complications in esophageal surgery patients: Randomized control trial to investigate therapeutic impact of anesthesia management and usefulness of simple blood test for prediction of high-risk patients

BACKGROUND: Oxidative stress may be an integral determinant of surgical stress severity. We examined whether the preoperative level of derivatives of reactive oxygen metabolites (d-ROMs), an oxidative stress biomarker based on total hydroperoxides in circulating blood, is predictive of increased risk of delayed recovery and complications after surgery, as well as the effects of anesthesia management on postoperative recovery in light of oxidative stress. METHODS: Patients (American Society of Anesthesiologists physical status I-II) scheduled for a radical esophagectomy (n = 186) were randomly selected to receive inhalational sevoflurane (n = 94) or intravenous propofol (n = 92) anesthesia. Preoperative blood d-ROMs level, as well as pre-and postoperative plasma ferric-reducing ability, were analyzed to assess oxidative stress, with white blood cell (WBC) count, C-reactive protein (CRP) level, incidence of severe postoperative complications, and postoperative recovery process within 30 days after surgery also examined in a double-blind fashion. RESULTS: Postoperative normalization of WBC and CRP was extended in patients with elevated preoperative d-ROMs [WBC versus d-ROMs: correlation coefficient (r) = 0.58 P < .001; CRP versus d-ROMs: r = 0.46 P < .001]. Receiver operating characteristics analysis of d-ROMs in relation to incidence of severe postoperative complications revealed an optimum d-ROMs threshold value of 410 UCarr and that patients with ≥410 UCarr had a greater risk of complications as compared to those with lower values (odds ratio = 4.7). Plasma ferric-reducing ability was decreased by 61 ± 185 mmol·l(−1) (P < .001) after surgery, demonstrating development of surgery-related oxidative stress, the magnitude of which was positively correlated with preoperative d-ROMs level (r = 0.16, P = .043). A comparison of the 2 anesthesia management protocols showed that patients who received propofol, an antioxidant anesthetic, had no postoperative decrease in ferric-reducing ability, lower incidence of severe postoperative complications (7 of 92 versus 18 of 94, P = .030, odds ratio = 0.35), and faster uneventful recovery time (WBC normalization days 7.1 ± 5.2 versus 13.6 ± 10.2, P < .001) as compared to those who received sevoflurane. CONCLUSIONS: Elevated preoperative blood d-ROMs predicts greater intraoperative oxidative stress and increased postoperative complications with prolonged recovery, thus is useful for identifying high-risk patients for delayed and complicated surgical recovery. Reduction of oxidative stress is vital for enhanced recovery, with control by antioxidants such as propofol a possible solution.