From the Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil (ASN, PPZAC), the Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (ASN, PPZAC, SNTH, LDB, MJS), the Program of Post-Graduation, Innovation and Research, Faculdade de Medicina do ABC, Santo André, Brazil (ASN), the Department of Anesthesiology (SNTH, MWH), the Laboratory of Experimental Intensive Care and Anesthesiology, University of Amsterdam, Amsterdam, The Netherlands (LDB, AMTB, MJS), the Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (TB, AG, TK, MGA), the Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany (MF), the Department of Anaesthesiology, Hospital de Sant Pau, Barcelona, Spain (II, CU), the Department of Anaesthesiology, University Hospital Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany (RL), the Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota (JS, TNW), the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA (DS, MFVM), and the Department of Surgical Sciences and Integrated Diagnostics, IRCCS San Martino IST, University of Genoa, Genoa, Italy (PP).
Eur J Anaesthesiol. 2017 Apr;34(4):229-238. doi: 10.1097/EJA.0000000000000614.
Postoperative pulmonary complications (PPCs) are common after major abdominal surgery. The kinetics of plasma biomarkers could improve identification of patients developing PPCs, but the kinetics may depend on intraoperative ventilator settings.
To test whether the kinetics of plasma biomarkers are capable of identifying patients who will develop PPCs, and whether the kinetics depend on the intraoperative level of positive end-expiratory pressure (PEEP).
A preplanned substudy of a randomised controlled trial.
Operation room of five centres.
Two hundred and forty-two adult patients scheduled for abdominal surgery at risk of developing PPCs.
High (12 cmH2O) versus low (≤2 cmH2O) levels of PEEP.
Individual PPCs were combined as a composite endpoint. Plasma samples were collected before surgery, directly after surgery and on the fifth postoperative day. The levels of the following were measured: tumour necrosis factor (TNF)-α, interleukin (IL)-6 and IL-8, the soluble form of the Receptor for Advanced Glycation End-products (sRAGE), Surfactant Protein (SP)-D, Clara Cell protein (CC)-16 and Krebs von den Lungen 6 (KL6).
Blood sampling was complete in 242 patients: 120 patients in the high PEEP group and 122 patients in the low PEEP group. Increases in plasma levels of TNF- IL-6, IL-8 and CC-16, and a decrease in plasma levels of SP-D were greater in patients who developed PPCs; however, the area under the receiver operating characteristic curve was low for all biomarkers. CC-16 was the only biomarker whose level increased more in patients who had received high levels of PEEP.
In patients undergoing abdominal surgery and at risk of developing PPCs, plasma levels of biomarkers for inflammation or lung injury showed distinct kinetics with development of PPCs, but none of the biomarkers showed sufficient prognostic value. The use of high levels of PEEP was associated with increased levels of CC-16, suggesting lung overdistension.
The PROVHILO trial, including this substudy, was registered at clinicaltrials.gov (NCT01441791).
术后肺部并发症(PPCs)是腹部大手术后常见的并发症。血浆生物标志物的动力学变化可以提高对发生 PPCs 患者的识别能力,但动力学变化可能取决于术中呼吸机设置。
检测血浆生物标志物的动力学变化是否能够识别将要发生 PPCs 的患者,以及动力学变化是否取决于术中呼气末正压(PEEP)水平。
一项随机对照试验的预先计划的亚研究。
五家中心的手术室。
242 名接受腹部手术且有发生 PPCs 风险的成年患者。
高(12cmH2O)与低(≤2cmH2O)水平的 PEEP。
将单个 PPCs 合并为一个复合终点。在手术前、手术后直接和术后第五天采集血浆样本。测量以下指标的水平:肿瘤坏死因子(TNF)-α、白细胞介素(IL)-6 和 IL-8、晚期糖基化终产物受体的可溶性形式(sRAGE)、表面活性蛋白(SP)-D、克拉拉细胞蛋白(CC)-16 和克雷布斯 von den Lungen 6(KL6)。
242 名患者的血液采样完整:高 PEEP 组 120 名,低 PEEP 组 122 名。发生 PPCs 的患者血浆中 TNF-α、IL-6、IL-8 和 CC-16 水平升高,SP-D 水平降低;然而,所有生物标志物的受试者工作特征曲线下面积均较低。CC-16 是唯一在接受高 PEEP 水平的患者中水平升高更多的生物标志物。
在接受腹部手术且有发生 PPCs 风险的患者中,炎症或肺损伤的生物标志物的血浆水平随着 PPCs 的发生表现出明显的变化,但没有一种生物标志物显示出足够的预后价值。高水平 PEEP 的使用与 CC-16 水平升高相关,提示肺过度膨胀。
包括这项亚研究在内的 PROVHILO 试验在 clinicaltrials.gov(NCT01441791)注册。