Spragg Roger G, Lewis James F, Walmrath Hans-Dieter, Johannigman Jay, Bellingan Geoff, Laterre Pierre-Francois, Witte Michael C, Richards Guy A, Rippin Gerd, Rathgeb Frank, Häfner Dietrich, Taut Friedemann J H, Seeger Werner
University of California at San Diego, Veterans Affairs Medical Center, San Diego 92014, USA.
N Engl J Med. 2004 Aug 26;351(9):884-92. doi: 10.1056/NEJMoa033181.
Preclinical studies suggest that exogenous surfactant may be of value in the treatment of the acute respiratory distress syndrome (ARDS), and two phase 2 clinical trials have shown a trend toward benefit. We conducted two phase 3 studies of a protein-containing surfactant in adults with ARDS.
In two multicenter, randomized, double-blind trials involving 448 patients with ARDS from various causes, we compared standard therapy alone with standard therapy plus up to four intratracheal doses of a recombinant surfactant protein C-based surfactant given within a period of 24 hours.
The overall survival rate was 66 percent 28 days after treatment, and the median number of ventilator-free days was 0 (68 percent range, 0 to 26); there was no significant difference between the groups in terms of mortality or the need for mechanical ventilation. Patients receiving surfactant had a significantly greater improvement in blood oxygenation during the initial 24 hours of treatment than patients receiving standard therapy, according to both univariate and multivariate analyses.
The use of exogenous surfactant in a heterogeneous population of patients with ARDS did not improve survival. Patients who received surfactant had a greater improvement in gas exchange during the 24-hour treatment period than patients who received standard therapy alone, suggesting the potential benefit of a longer treatment course.
临床前研究表明，外源性表面活性剂可能对急性呼吸窘迫综合征（ARDS）的治疗有价值，两项2期临床试验已显示出有益的趋势。我们对含蛋白质的表面活性剂在成年ARDS患者中进行了两项3期研究。
在两项多中心、随机、双盲试验中，纳入了448例因各种原因导致ARDS的患者，我们将单纯标准治疗与标准治疗加在24小时内给予多达4次气管内剂量的基于重组表面活性蛋白C的表面活性剂进行了比较。
治疗28天后的总生存率为66%，无呼吸机天数的中位数为0（68%的范围为0至26）；两组在死亡率或机械通气需求方面无显著差异。根据单变量和多变量分析，接受表面活性剂治疗的患者在治疗的最初24小时内血液氧合的改善明显大于接受标准治疗的患者。
在异质性ARDS患者群体中使用外源性表面活性剂并未提高生存率。接受表面活性剂治疗的患者在24小时治疗期间的气体交换改善大于单纯接受标准治疗的患者，这表明延长治疗疗程可能有益。
