Raymondos K, Leuwer M, Haslam P L, Vangerow B, Ensink M, Tschorn H, Schürmann W, Husstedt H, Rueckoldt H, Piepenbrock S
Department of Anesthesia, University Hospital, Hanover, Germany.
Crit Care Med. 1999 Jan;27(1):82-9. doi: 10.1097/00003246-199901000-00031.
Sepsis is one of the most important predisposing factors for the development of the acute respiratory distress syndrome (ARDS). Alterations of pulmonary surfactant contribute in the pathogenesis of ARDS. However, little is known about surfactant in patients with less severe grades of lung injury related to sepsis or systemic inflammatory response syndrome (SIRS). Therefore, the purpose of this study was to characterize endogenous surfactant in surgical intensive care patients with sepsis or SIRS.
Prospective, observational study.
University-affiliated, interdisciplinary intensive care unit.
Eleven patients after major surgery with SIRS or sepsis included within 12 hrs of onset and 11 controls without infection or lung disease.
Operating room and standard intensive care unit management.
Four serial bronchoalveolar lavage samples (BAL) were recovered over 7 days from the patients and single BAL samples were obtained from controls. BAL cells, total protein, surfactant-associated protein A (SP-A), surfactant alveolar transition forms, and surface activity were analyzed. Two of 11 patients met criteria for acute lung injury and six of the 11 patients met ARDS consensus conference criteria but acute lung injury or ARDS was not persistent. The mean Pao2/F(IO)2 for the patients over 7 days was 253.2+/-15.1 (SEM) and Murray's lung injury score was 1.12+/-0.12, indicating mild-to-moderate lung injury. BAL neutrophil counts were increased (p< .01), and the ratio of poorly functioning light aggregate surfactant to superiorly functioning heavy aggregate surfactant was increased compared with controls (0.32+/-0.06 vs. 0.09+/-0.01, p < .05). SP-A was decreased (1.9+/-0.4 vs. 3.5+/-0.6 microg/mL of BAL, p< .05) and there were increases in the ratios of phospholipid to SP-A (p < .05), protein to SP.A (p < .01), and protein to phospholipid (p < .05). The surface tension-lowering ability of purified heavy aggregate surfactant was significantly impaired (15.6+/-1.6 vs. 2.8+/-0.6 milliNewtons/m, p< .05).
These observations show that surgical patients with SIRS or sepsis who have mild-to-moderate lung injury develop surfactant dysfunction detectable within 7 days of onset. We propose, therefore, that therapeutic strategies to modulate these severe surfactant abnormalities should be considered, as these strategies may have the potential to reduce lung injury, which is associated with a high mortality in sepsis.
脓毒症是急性呼吸窘迫综合征（ARDS）发生的最重要诱发因素之一。肺表面活性物质的改变参与了ARDS的发病机制。然而，对于与脓毒症或全身炎症反应综合征（SIRS）相关的较轻程度肺损伤患者的表面活性物质了解甚少。因此，本研究的目的是对患有脓毒症或SIRS的外科重症监护患者的内源性表面活性物质进行特征描述。
前瞻性观察性研究。
大学附属医院的跨学科重症监护病房。
11例重大手术后发生SIRS或脓毒症的患者，发病后12小时内纳入研究，11例无感染或肺部疾病的对照者。
手术室和标准重症监护病房管理。
在7天内从患者处采集4份连续的支气管肺泡灌洗样本（BAL），从对照者处采集单份BAL样本。对BAL细胞、总蛋白、表面活性物质相关蛋白A（SP-A）、表面活性物质肺泡转化形式及表面活性进行分析。11例患者中有2例符合急性肺损伤标准，11例患者中有6例符合ARDS共识会议标准，但急性肺损伤或ARDS并非持续性的。患者7天内的平均Pao2/F(IO)2为253.2±15.1（标准误），默里肺损伤评分为1.12±0.12，表明为轻至中度肺损伤。BAL中性粒细胞计数增加（p<0.01），与对照组相比，功能较差的轻聚集体表面活性物质与功能较好的重聚集体表面活性物质的比例增加（0.32±0.06 vs. 0.09±0.01，p<0.05）。SP-A降低（BAL中为1.9±0.4 vs. 3.5±0.6μg/mL，p<0.05），磷脂与SP-A的比例（p<0.05）、蛋白与SP-A的比例（p<0.01）以及蛋白与磷脂的比例（p<0.05）均增加。纯化的重聚集体表面活性物质降低表面张力的能力明显受损（15.6±1.6 vs. 2.8±0.6毫牛顿/米，p<0.05）。
这些观察结果表明，患有轻至中度肺损伤的SIRS或脓毒症外科患者在发病7天内出现可检测到的表面活性物质功能障碍。因此，我们建议应考虑采用调节这些严重表面活性物质异常的治疗策略，因为这些策略可能有降低肺损伤的潜力，而肺损伤在脓毒症中与高死亡率相关。
