Tsuchiya Masahiko, Shiomoto Kazumasa, Mizutani Koh, Fujioka Kazuya, Suehiro Koichi, Yamada Tokuhiro, Sato Eisuke F, Nishikawa Kiyonobu
Department of Anesthesiology, Osaka City University Graduate School of Medicine.
Department of Clinical Laboratory, Osaka City University Hospital, Abeno-Ku, Osaka, Japan.
Medicine (Baltimore). 2018 Nov;97(47):e12845. doi: 10.1097/MD.0000000000012845.
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.
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.
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 (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.
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.
氧化应激可能是手术应激严重程度的一个重要决定因素。我们研究了活性氧代谢产物衍生物（d-ROMs）的术前水平，一种基于循环血液中总氢过氧化物的氧化应激生物标志物，是否能预测术后恢复延迟和并发症风险增加，以及根据氧化应激探讨麻醉管理对术后恢复的影响。
计划行根治性食管切除术的患者（美国麻醉医师协会身体状况I-II级，n = 186）被随机选择接受吸入七氟醚（n = 94）或静脉丙泊酚（n = 92）麻醉。分析术前血液d-ROMs水平以及术前和术后血浆铁还原能力以评估氧化应激，同时以双盲方式检查白细胞（WBC）计数、C反应蛋白（CRP）水平、严重术后并发症发生率以及术后30天内的恢复过程。
术前d-ROMs升高的患者术后WBC和CRP的正常化时间延长[WBC与d-ROMs：相关系数（r）= 0.58，P <.001；CRP与d-ROMs：r = 0.46，P <.001]。d-ROMs与严重术后并发症发生率的受试者工作特征分析显示，d-ROMs的最佳阈值为410 UCarr，≥410 UCarr的患者与较低值患者相比并发症风险更高（比值比 = 4.7）。术后血浆铁还原能力降低了61 ± 185 mmol·l（P <.001），表明发生了与手术相关的氧化应激，其程度与术前d-ROMs水平呈正相关（r = 0.16，P =.043）。两种麻醉管理方案的比较显示接受丙泊酚（一种抗氧化麻醉剂）的患者术后铁还原能力没有下降，严重术后并发症发生率较低（92例中的7例与94例中的18例，P =.030，比值比 = 0.35），与接受七氟醚的患者相比，平稳恢复时间更快（WBC正常化天数7.1 ± 5.2与13.6 ± 10.2，P <.001）。
术前血液d-ROMs升高预示术中氧化应激更大，术后并发症增加且恢复延长，因此有助于识别手术恢复延迟和复杂的高危患者。减轻氧化应激对促进恢复至关重要，使用丙泊酚等抗氧化剂进行控制可能是一种解决方案。
