Scheffzük Claudia, Lührmann Johanna, Brinkmann Robin, Biedziak Dominika, Gloystein Kristina, Kellner Patrick, Stamme Cordula
Division of Cellular Pneumology, Priority Area Infections, Research Center Borstel, Leibniz Lung Center, Borstel, 23845, Germany.
Department of Anesthesiology and Intensive Care Medicine, University Hospital of Schleswig-Holstein, Lübeck, 23538, Germany.
BMC Pulm Med. 2025 Sep 9;25(1):425. doi: 10.1186/s12890-025-03849-w.
Volatile anesthetics are gaining recognition for their benefits in long-term sedation of mechanically ventilated patients with bacterial pneumonia and acute respiratory distress syndrome. In addition to their sedative role, they also exhibit anti-bacterial and anti-inflammatory properties, though the mechanisms behind these effects remain only partially understood. In vitro studies examining the prolonged impact of volatile anesthetics on bacterial growth, inflammatory cytokine response, and surfactant proteins - key to maintaining lung homeostasis - are still lacking.
Using an anaerobic chamber setup, we evaluated the effects of the most commonly used volatile anesthetics, Sevoflurane and Desflurane, at clinically relevant concentrations on the growth of Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. Bacterial growth was monitored over 24 h, assessing OD, CFU/ml, and growth rate during the log phase. In the same setup, but with aerobic conditions, we investigated the immunomodulatory properties of both anesthetics on human A549 cells, either with or without bacterial lipopolysaccharide (LPS, 1 µg/ml) stimulation. Over 48 h, we analyzed pro-inflammatory chemokine release using ELISA and assessed surfactant protein expression with Western blot analysis.
Sevoflurane and Desflurane significantly reduced Pseudomonas aeruginosa growth as expressed consistently in OD and CFU/ml starting after 12 h. Both volatile anesthetics also significantly reduced Staphylococcus aureus OD starting after 21 h. Sevoflurane (p < 0.01) and Desflurane (p < 0.001) counteracted LPS-induced interleukin-8 release by A549 cells after 48 h and significantly ( p < 0.01 and p < 0.05) enhanced the expression of the propeptide of surfactant protein C after 24 h.
Prolonged anti-bacterial and anti-inflammatory effects of Sevoflurane and Desflurane include both the reduction of Pseudomonas aeruginosa and Staphylococcus aureus growth as well as the inhibition of LPS-induced chemokine release by A549 epithelial cells paralleled by an increase of surfactant protein expression. These effects highlight the potential of volatile anesthetics beyond sedation in supporting lung function in ventilated patients with respiratory failure.
挥发性麻醉剂在机械通气的细菌性肺炎和急性呼吸窘迫综合征患者的长期镇静中的益处正得到认可。除了其镇静作用外,它们还具有抗菌和抗炎特性,尽管这些作用背后的机制仍仅部分为人所知。目前仍缺乏体外研究来考察挥发性麻醉剂对细菌生长、炎性细胞因子反应以及表面活性蛋白(维持肺稳态的关键因素)的长期影响。
我们使用厌氧箱装置,评估了临床相关浓度下最常用的挥发性麻醉剂七氟烷和地氟烷对铜绿假单胞菌、大肠杆菌和金黄色葡萄球菌生长的影响。在24小时内监测细菌生长情况,评估对数期的光密度(OD)、每毫升菌落形成单位(CFU/ml)和生长速率。在相同装置但有氧条件下,我们研究了这两种麻醉剂对人A549细胞的免疫调节特性,无论有无细菌脂多糖(LPS,1μg/ml)刺激。在48小时内,我们使用酶联免疫吸附测定(ELISA)分析促炎趋化因子的释放,并通过蛋白质免疫印迹分析评估表面活性蛋白的表达。
七氟烷和地氟烷显著降低了铜绿假单胞菌的生长,从12小时后OD和CFU/ml的结果可一致体现。两种挥发性麻醉剂在21小时后也显著降低了金黄色葡萄球菌的OD。48小时后,七氟烷(p < 0.01)和地氟烷(p < 0.001)抵消了LPS诱导的A549细胞白细胞介素 - 8释放,并且在24小时后显著(p < 0.01和p < 0.05)增强了表面活性蛋白C前体肽的表达。
七氟烷和地氟烷的长期抗菌和抗炎作用包括降低铜绿假单胞菌和金黄色葡萄球菌的生长,以及抑制LPS诱导的A549上皮细胞趋化因子释放,同时伴随着表面活性蛋白表达增加。这些作用凸显了挥发性麻醉剂在支持呼吸衰竭通气患者肺功能方面除镇静作用之外的潜力。