术前生物学表型与术后肺部并发症的关系：一项无偏聚类分析。

Association between pre-operative biological phenotypes and postoperative pulmonary complications: An unbiased cluster analysis.

机构信息

From the Department of Critical Care Medicine, Hospital Israelita Albert Einstein, São Paulo, Brazil (ASN, PPZAC), Department of Intensive Care, Academic Medical Center (ASN, LDB, PPZAC, SNTH, MJS), Laboratory of Experimental Intensive Care and Anesthesiology, Academic Medical Center (LDB, MJS), Department of Anesthesiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands (SNTH, MWH, AMT-dB), Department of Anesthesiology and Intensive Care Medicine, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany (TB, AG, TK, MGdA), Division of Pulmonary and Critical Care Medicine, Departments of Medicine and Anesthesia, University of California, San Francisco, San Francisco, California, USA (CSC), Interdisciplinary Center for Clinical Trials (IZKS), University Medical Center of the Johannes Gutenberg-University Mainz, Mainz, Germany (MF), Department of Anaesthesiology, Hospital de Sant Pau, Barcelona, Spain (II), Department of Anaesthesiology, University Hospital Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany (RL-F), Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota (JS, TNW), Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA (DS, MFVM), Department of Surgical Sciences and Integrated Diagnostics, IRCCS San Martino IST, University of Genoa, Genoa, Italy (PP) and Mahidol Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand (MJS). PROVHILO = PROtective Ventilation with HIgh or LOw PEEP-trial. PROVE = PROtective VEntilation (http://www.provenet.eu).

出版信息

Eur J Anaesthesiol. 2018 Sep;35(9):702-709. doi: 10.1097/EJA.0000000000000846.

DOI:10.1097/EJA.0000000000000846

PMID:29957706

Abstract

BACKGROUND

Biological phenotypes have been identified within several heterogeneous pulmonary diseases, with potential therapeutic consequences.

OBJECTIVE

To assess whether distinct biological phenotypes exist within surgical patients, and whether development of postoperative pulmonary complications (PPCs) and subsequent dependence of intra-operative positive end-expiratory pressure (PEEP) differ between such phenotypes.

SETTING

Operating rooms of six hospitals in Europe and USA.

DESIGN

Secondary analysis of the 'PROtective Ventilation with HIgh or LOw PEEP' trial.

PATIENTS

Adult patients scheduled for abdominal surgery who are at risk of PPCs.

INTERVENTIONS

Measurement of pre-operative concentrations of seven plasma biomarkers associated with inflammation and lung injury.

MAIN OUTCOME MEASURES

We applied unbiased cluster analysis to identify biological phenotypes. We then compared the proportion of patients developing PPCs within each phenotype, and associations between intra-operative PEEP levels and development of PPCs among phenotypes.

RESULTS

In total, 242 patients were included. Unbiased cluster analysis clustered the patients within two biological phenotypes. Patients with phenotype 1 had lower plasma concentrations of TNF-α (3.8 [2.4 to 5.9] vs. 10.2 [8.0 to 12.1] pg ml; P < 0.001), IL-6 (2.3 [1.5 to 4.0] vs. 4.0 [2.9 to 6.5] pg ml; P < 0.001) and IL-8 (4.7 [3.1 to 8.1] vs. 8.1 [6.0 to 13.9] pg ml; P < 0.001). Phenotype 2 patients had the highest incidence of PPC (69.8 vs. 34.2% in type 1; P < 0.001). There was no interaction between phenotype and PEEP level for the development of PPCs (43.2% in high PEEP vs. 25.6% in low PEEP in phenotype 1, and 73.6% in high PEEP and 65.7% in low PEEP in phenotype 2; P for interaction = 0.503).

CONCLUSION

Patients at risk of PPCs and undergoing open abdominal surgery can be clustered based on pre-operative plasma biomarker concentrations. The two identified phenotypes have different incidences of PPCs. Biologic phenotyping could be useful in future randomised controlled trials of intra-operative ventilation.

TRIAL REGISTRATION

The PROtective Ventilation with HIgh or LOw PEEP trial, including the substudy from which data were used for the present analysis, was registered at ClinicalTrials.gov (NCT01441791).

摘要

背景

已经在几种异质性肺部疾病中确定了生物学表型，其具有潜在的治疗意义。

目的

评估手术患者中是否存在不同的生物学表型，以及这些表型之间术后肺部并发症（PPC）的发生和术中正呼气末压（PEEP）的依赖是否存在差异。

地点

欧洲和美国的六家医院的手术室。

设计

对“保护性通气高或低 PEEP 试验”的二次分析。

患者

计划接受腹部手术且有 PPC 风险的成年患者。

干预措施

测量术前七种与炎症和肺损伤相关的血浆生物标志物的浓度。

主要观察指标

我们应用无偏聚类分析来识别生物学表型。然后，我们比较了每个表型中发生 PPC 的患者比例，以及表型之间术中 PEEP 水平与 PPC 发生之间的关系。

结果

共纳入 242 例患者。无偏聚类分析将患者分为两种生物学表型。表型 1 患者的 TNF-α（3.8 [2.4 至 5.9] vs. 10.2 [8.0 至 12.1] pg/ml；P < 0.001）、IL-6（2.3 [1.5 至 4.0] vs. 4.0 [2.9 至 6.5] pg/ml；P < 0.001）和 IL-8（4.7 [3.1 至 8.1] vs. 8.1 [6.0 至 13.9] pg/ml；P < 0.001）血浆浓度较低。表型 2 患者 PPC 发生率最高（69.8% vs. 表型 1 中的 34.2%；P < 0.001）。表型和 PEEP 水平对 PPC 发生无交互作用（表型 1 中高 PEEP 组为 43.2%，低 PEEP 组为 25.6%，表型 2 中高 PEEP 组为 73.6%，低 PEEP 组为 65.7%；P 交互作用=0.503）。