肥胖手术患者肺损伤血浆生物标志物与呼气末正压及术后肺部并发症的关联：PROBESE随机对照试验的一项子研究

Association of plasma biomarkers of lung injury with positive end expiratory pressure and postoperative pulmonary complications in obese surgical patients: A substudy of the PROBESE randomised controlled trial.

作者信息

Bluth Thomas, Rivas Eva, López-Baamonde Manuel, Sanahuja Josep Martí, López-Hernández Antonio, Balust Jaume, Weingarten Toby N, Girrbach Felix, Simon Philipp, Wrigge Hermann, Wittenstein Jakob, Birr Katharina, Teichmann Robert, Huhle Robert, Melchior Niklas, Vivona Luigi, Koch Thea, Ramakrishna Harish, Brull Sorin, Serpa Neto Ary, Schultz Marcus J, Sprung Juraj, Scharffenberg Martin, Gama de Abreu Marcelo

机构信息

From the Department of Anaesthesiology and Intensive Care Medicine, Pulmonary Engineering Group, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany ((TB, JW, KB, RT, RH, NM, LV, TK, MS, MGdA), Department of Anaesthesiology, Hospital Clínic, Barcelona, Spain (ER, ML-B, JMS, AL-H, JB), Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio (ER, MGdA), Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota, USA (TNW, JS), Department of Anaesthesiology and Intensive Care, University of Leipzig Medical Center, Leipzig (FG, PS, HW), Anesthesiology and Operative Intensive Care, Faculty of Medicine, University of Augsburg, Augsburg (FG, PS), Department of Anesthesiology, Intensive Care and Emergency Medicine, Pain Therapy, Bergmannstrost Hospital, Halle, Germany (HW), Department of Pathophysiology and Transplantation, University of Milan, Italy (LV), Mayo Clinic Arizona, Phoenix, Arizona (HR), Department of Anesthesiology and Perioperative Medicine, College of Medicine, Mayo Clinic, Jacksonville, Florida, USA (Sorin Brull), Australian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine, Monash University (ASN), Department of Intensive Care (ASN), Department of Critical Care, Melbourne Medical School, University of Melbourne, Austin Hospital, Melbourne, Victoria, Australia (ASN), Department of Critical Care Medicine, Hospital Israelita Albert Einstein, Sao Paulo, Brazil (ASN), Department of Intensive Care, Amsterdam UMC Location AMC, Amsterdam, The Netherlands (MJS), Mahidol-Oxford Tropical Medicine Research Unit (MORU), Mahidol University, Bangkok, Thailand (MJS), Nuffield Department of Medicine, University of Oxford, Oxford, UK (MJS), Department of Anesthesia, General Intensive Care and Pain Management, Division of Cardiothoracic and Vascular Anesthesia & Critical Care Medicine, Medical University of Vienna, Vienna, Austria (MJS), Department of Intensive Care and Resuscitation, Anesthesiology Institute, Cleveland Clinic, Cleveland, Ohio, USA (MGdA).

出版信息

Eur J Anaesthesiol. 2025 Sep 1;42(9):840-850. doi: 10.1097/EJA.0000000000002221. Epub 2025 Jun 20.

DOI:10.1097/EJA.0000000000002221

PMID:40548583

Abstract

BACKGROUND

The effect of positive end expiratory pressure (PEEP) on postoperative pulmonary complications (PPCs) in obese patients remains controversial.

OBJECTIVE

To test, whether intra-operative PEEP or PPCs are associated with plasma levels of biomarkers of lung injury.

DESIGN

A prospective substudy of a multicentre randomised controlled trial (PROBESE).

SETTING

Operating rooms of six tertiary care centres in the United States and Europe.

PATIENTS

Obese patients at risk for PPCs undergoing abdominal surgery.

INTERVENTION

Intra-operative low tidal volume ventilation with high PEEP (12 cmH 2 O) and recruitment manoeuvres, or low PEEP (4 cmH 2 O).

MAIN OUTCOME MEASURES

The primary endpoint was the association between absolute postoperative plasma levels of receptor for advanced glycation end-products (RAGE) and intra-operative PEEP; secondary endpoints included pre and postoperative plasma concentrations as well as the relative changes of interleukin-6, IL-8, tumour necrosis factor-α, surfactant protein D, mucin-1, clara cell protein-16, intercellular adhesion molecule-1 and vascular cell adhesion molecule. PPCs were assessed as a 'collapsed composite' of adverse pulmonary events. The predictive ability of biomarkers for PPCs was assessed with the receiver operating curve-area under the curve (ROC-AUC).

RESULTS

A total of 96 patients received low PEEP, and 95 patients high PEEP. Postoperative plasma concentrations of RAGE and other biomarkers did not differ between groups. The relative increase of RAGE during surgery was more pronounced with low than high PEEP; median [IQR], 1.2 [1.0 to 1.6] vs. 1.1 [0.9 to 1.3], P = 0.012. Patients who developed PPCs showed higher postoperative plasma levels and relative increase of IL-6; 26.3 [12.6 to 139.5] vs. 15.1 [3.7 to 38.7] fold change. The ROC-AUC was less than 0.7 for all biomarkers.

CONCLUSIONS

In this subgroup, choice of PEEP did not affect postoperative biomarkers of lung injury. Irrespective of PEEP, PPCs were associated with an increase in plasma levels of these biomarkers, but their predictive capability was poor.

TRIAL REGISTRATION

Clinicaltrials.gov, identifier: NCT02148692.

摘要

背景

呼气末正压通气（PEEP）对肥胖患者术后肺部并发症（PPCs）的影响仍存在争议。

目的

测试术中PEEP或PPCs是否与肺损伤生物标志物的血浆水平相关。

设计

一项多中心随机对照试验（PROBESE）的前瞻性子研究。

地点

美国和欧洲六个三级医疗中心的手术室。

患者

有PPCs风险且接受腹部手术的肥胖患者。

干预

术中采用低潮气量通气加高水平PEEP（12 cmH₂O）及肺复张手法，或低水平PEEP（4 cmH₂O）。

主要观察指标

主要终点是术后晚期糖基化终末产物受体（RAGE）的绝对血浆水平与术中PEEP之间的关联；次要终点包括术前和术后血浆浓度以及白细胞介素-6、白细胞介素-8、肿瘤坏死因子-α、表面活性蛋白D、粘蛋白-1、克拉拉细胞蛋白-16、细胞间粘附分子-1和血管细胞粘附分子的相对变化。PPCs被评估为不良肺部事件的“综合指标”。采用受试者工作特征曲线下面积（ROC-AUC）评估生物标志物对PPCs的预测能力。

结果

共有96例患者接受低水平PEEP，95例患者接受高水平PEEP。两组术后血浆中RAGE和其他生物标志物的浓度无差异。术中RAGE的相对升高在低水平PEEP组比高水平PEEP组更明显；中位数[四分位间距]，1.2[1.0至1.6]对1.1[0.9至1.3]，P = 0.012。发生PPCs的患者术后血浆中IL-6水平及相对升高更高；变化倍数为26.3[12.6至139.5]对15.1[3.7至38.7]。所有生物标志物的ROC-AUC均小于0.7。