Veterans Affairs Medical Center, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Am J Respir Crit Care Med. 2011 Apr 15;183(8):1055-61. doi: 10.1164/rccm.201009-1424OC. Epub 2010 Dec 10.
Patients with acute lung injury have impaired function of the lung surfactant system. Prior clinical trials have shown that treatment with exogenous recombinant surfactant protein C (rSP-C)-based surfactant results in improvement in blood oxygenation and have suggested that treatment of patients with severe direct lung injury may decrease mortality.
Determine the clinical benefit of administering an rSP-C-based synthetic surfactant to patients with severe direct lung injury due to pneumonia or aspiration.
A prospective randomized blinded study was performed at 161 centers in 22 countries. Patients were randomly allocated to receive usual care plus up to eight doses of rSP-C surfactant administered over 96 hours (n = 419) or only usual care (n = 424).
Mortality to 28 days after treatment, the requirement for mechanical ventilation, and the number of nonpulmonary organ failure-free days were not different between study groups. In contrast to prior studies, there was no improvement in oxygenation in patients receiving surfactant compared with the usual care group. Investigation of the possible reasons underlying the lack of efficacy suggested a partial inactivation of rSP-C surfactant caused by a step of the resuspension process that was introduced with this study.
In this study, rSP-C-based surfactant was of no clinical benefit to patients with severe direct lung injury. The unexpected lack of improvement in oxygenation, coupled with the results of in vitro tests, suggest that the administered suspension may have had insufficient surface activity to achieve clinical benefit.
急性肺损伤患者的肺表面活性物质系统功能受损。先前的临床试验表明，使用外源性重组表面活性蛋白 C（rSP-C）为基础的表面活性物质治疗可改善血氧，并表明治疗严重直接肺损伤患者可能降低死亡率。
确定 rSP-C 为基础的合成表面活性物质治疗因肺炎或吸入导致的严重直接肺损伤患者的临床益处。
在 22 个国家的 161 个中心进行了前瞻性随机对照盲法研究。患者随机分配接受常规治疗加 96 小时内最多 8 次 rSP-C 表面活性物质治疗（n = 419）或仅接受常规治疗（n = 424）。
治疗后 28 天的死亡率、机械通气的需求以及非肺部器官衰竭无天数均在研究组之间无差异。与先前的研究相比，接受表面活性物质治疗的患者的氧合情况没有改善，与常规治疗组相比。对疗效缺乏的可能原因进行调查表明，rSP-C 表面活性物质的部分失活是由于该研究引入的重悬过程中的一个步骤所致。
在这项研究中，rSP-C 为基础的表面活性物质对严重直接肺损伤患者没有临床益处。出乎意料的是，氧合改善不明显，加上体外试验的结果，表明给予的混悬液可能表面活性不足，无法获得临床益处。
