猪肺表面活性物质治疗胎粪吸入综合征的多中心随机对照研究

Treatment of severe meconium aspiration syndrome with porcine lung-derived surfactant: a multicenter, randomized, controlled trial

目的在中国19家新生儿重症监护病房开展猪肺表面活性物质治疗足月儿或近足月儿重症胎粪吸入综合征(MAS)多中心随机对照临床试验,判断其疗效和安全性。方法61例重症MAS患儿在生后36h内入选试验,随机分为表面活性物质治疗组(PS,n=31)和对照组(C,n=30)。PS首剂给药量为200mg/(kg·w),重复给药时追加剂量为200、100、100mg/kg。主要疗效评估指标为PS治疗后24h氧合指数(OI)小于10,动脉/肺泡氧分压比值(a/APO2)较用药前基础值增加100%;次要评估指标为机械通气时间、并发症发生率和存活出院的患儿数。结果两组患儿一般临床特征相似。在随机化治疗后24h,与C组相比,PS组平均OI值降低(10.9vs.8.1)、有较多患儿a/APO2较基础值增加100%(48%vs.83%,P<0.01)、PaO2/FiO2曲线下面积更大[(3762±1877)vs.(2715±1644)mmHg·h(P<0.05,1mmHg=0.133kPa)]。在治疗的3、7天,上述参数PS组仍优于C组。两组间在机械通气时间、主要并发症发生率和存活率上差异无统计学意义。结论表面活性物质治疗重症MAS能改善氧合,不增加并发症的发生。

Objective A randomized controlled clinical trial was performed in nineteen Chinese neonatal intensive care units to evaluate the safety and efficacy of exogenous surfactant replacement therapy for severe meconium aspiration syndrome (MAS) in term and near-term neonates.Methods During the period from March 22, 2001 to April 4, 2003, 61 term infants with severe MAS were randomly assigned to either a surfactant or a control group within 36 h after birth. The infants in the surfactant group (n=31) received an initial dose of porcine lung-derived surfactant (Curosurf) at 200 mg/kg, and repeated doses of 200, 100 and 100 mg/kg were given at 6—12 h intervals to a maximum of four doses if oxygenation index (OI) deteriorated by >2 from baseline. The primary outcomes were a reduction of OI to less than 10 and an increase of the pre-treatment a/A PO 2 ratio of 100% over baseline 24 h after surfactant treatment. The secondary outcomes were duration of mechanical ventilation, occurrence of complications and survival to discharge from hospital.Results The general demographic characteristics of the study subjects between the 2 groups were similar. There was a trend for surfactant-treated infants to have an improvement in arterial oxygenation compared to the control group. In comparison with the control group at 24 h, the surfactant group had a lower mean OI (8.1 vs. 10.9), more infants with a 100% increase of a/A PO 2 (83% vs. 48%, P<0.01) over baseline, and a larger area under the curve for PaO2/FiO2 over baseline [(3762±1877) vs. (2715±1644) mm Hg·h (P<0.05, 1 mm Hg=0.133 kPa)]. Repeated measures of these parameters were also in favor of surfactant group during 24 h to 3 and 7 days compared to the baseline (P<0.05). No significant differences were found in mean duration of mechanical ventilation (105±81 vs. 80±40), occurrence of major complications and survival rate (96.8% vs. 90.0%) between the surfactant and the control groups. Conclusion Surfactant replacement therapy improved oxygenation but did not increase complications in the study subjects, suggesting that surfactant may be effective and safe for treatment of severe MAS in term and near-term infants.