Faculty of Biology, Medicine and Health, School of Biological Sciences, University of Manchester, UK.
Department of Critical Care Medicine, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.
Anaesthesia. 2023 Jun;78(6):712-721. doi: 10.1111/anae.15999. Epub 2023 Apr 3.
Ventilator-associated pneumonia commonly occurs in critically ill patients. Clinical suspicion results in overuse of antibiotics, which in turn promotes antimicrobial resistance. Detection of volatile organic compounds in the exhaled breath of critically ill patients might allow earlier detection of pneumonia and avoid unnecessary antibiotic prescription. We report a proof of concept study for non-invasive diagnosis of ventilator-associated pneumonia in intensive care (the BRAVo study). Mechanically ventilated critically ill patients commenced on antibiotics for clinical suspicion of ventilator-associated pneumonia were recruited within the first 24 h of treatment. Paired exhaled breath and respiratory tract samples were collected. Exhaled breath was captured on sorbent tubes and then analysed using thermal desorption gas chromatography-mass spectrometry to detect volatile organic compounds. Microbiological culture of a pathogenic bacteria in respiratory tract samples provided confirmation of ventilator-associated pneumonia. Univariable and multivariable analyses of volatile organic compounds were performed to identify potential biomarkers for a 'rule-out' test. Ninety-six participants were enrolled in the trial, with exhaled breath available from 92. Of all compounds tested, the four highest performing candidate biomarkers were benzene, cyclohexanone, pentanol and undecanal with area under the receiver operating characteristic curve ranging from 0.67 to 0.77 and negative predictive values from 85% to 88%. Identified volatile organic compounds in the exhaled breath of mechanically ventilated critically ill patients show promise as a useful non-invasive 'rule-out' test for ventilator-associated pneumonia.
呼吸机相关性肺炎常发生于危重症患者。临床怀疑会导致抗生素过度使用，进而促进抗菌药物耐药性的产生。在危重症患者的呼气中检测挥发性有机化合物，可能有助于更早地发现肺炎并避免不必要的抗生素处方。我们报告了一项在重症监护中用于非侵入性诊断呼吸机相关性肺炎的概念验证研究（BRAVo 研究）。在开始抗生素治疗的 24 小时内，招募了因临床怀疑呼吸机相关性肺炎而开始接受抗生素治疗的机械通气危重症患者。采集配对的呼气和呼吸道样本。呼气被采集到吸附管中，然后使用热解吸气相色谱-质谱法进行分析，以检测挥发性有机化合物。呼吸道样本中致病性细菌的微生物培养提供了呼吸机相关性肺炎的确诊依据。对挥发性有机化合物进行单变量和多变量分析，以确定用于“排除”试验的潜在生物标志物。该试验共纳入 96 名参与者，其中 92 名参与者有呼气样本可用。在所有测试的化合物中，表现最好的四个候选生物标志物是苯、环己酮、戊醇和十一醛，其受试者工作特征曲线下面积范围为 0.67 至 0.77，阴性预测值为 85%至 88%。在机械通气的危重症患者的呼气中鉴定出的挥发性有机化合物显示出作为一种有用的非侵入性“排除”试验用于诊断呼吸机相关性肺炎的潜力。
