Division of Pediatric Critical Care Medicine, Penn State Hershey Children's Hospital, Pennsylvania State University College of Medicine, Hershey, PA, USA.
Pediatr Crit Care Med. 2012 Nov;13(6):646-53. doi: 10.1097/PCC.0b013e3182517bec.
Inhibition of surfactant function and abnormal surfactant synthesis lead to surfactant dysfunction in children with acute hypoxemic respiratory failure. We evaluated whether intratracheal lucinactant, a synthetic, peptide-containing surfactant, was safe and well-tolerated in infants with acute hypoxemic respiratory failure, and assessed its effects on clinical outcomes.
Infants ≤ 2 yrs of age with acute hypoxemic respiratory failure were enrolled in a phase II, double-blind, multinational, placebo-controlled randomized trial across 36 pediatric intensive care units. Infants requiring mechanical ventilation with persistent hypoxemia meeting acute lung injury criteria were randomized to receive intratracheal lucinactant (175 mg/kg) or air placebo. One retreatment was allowed 12-24 hrs after initial dosing if hypoxemia persisted. Peri-dosing tolerability of intratracheal lucinactant and adverse experiences were assessed. Mechanical ventilation duration was analyzed using analysis of variance. The Cochran-Mantel-Haenszel test was used for categorical variables.We enrolled 165 infants (84 lucinactant; 81 placebo) with acute hypoxemic respiratory failure. There were no significant differences in baseline subject characteristics, with the exception of a lower positive end-expiratory pressure and higher tidal volume in placebo subjects. The incidence of transient peri-dosing bradycardia and desaturation was significantly higher in the lucinactant treatment group. There were no statistical differences between groups for other adverse events or mortality. Oxygenation improved in infants randomized to receive lucinactant as indicated by fewer second treatments (67% lucinactant vs. 81% placebo, p = .02) and a trend in improvement in partial pressure of oxygen in arterial blood to fraction of inspired oxygen from eligibility to 48 hrs after dose (p = .06). There was no significant reduction in duration of mechanical ventilation with lucinactant (geometric least square means: 4.0 days lucinactant vs. 4.5 days placebo; p = .254). In a subset of infants (n = 22), the duration of mechanical ventilation in children with acute lung injury (partial pressure of oxygen in arterial blood to fraction of inspired oxygen >200) was significantly shorter with lucinactant (least square means: 2.4 days lucinactant vs. 4.3 days placebo; p = .006).
In mechanically ventilated infants with acute hypoxemic respiratory failure, treatment with intratracheal lucinactant appeared to be generally safe. An improvement in oxygenation and a significantly reduced requirement for retreatment suggests that lucinactant might improve lung function in infants with acute hypoxemic respiratory failure.
表面活性剂功能抑制和异常表面活性剂合成导致急性低氧性呼吸衰竭患儿的表面活性剂功能障碍。我们评估了气管内 lucinactant（一种合成的、含肽的表面活性剂）在急性低氧性呼吸衰竭婴儿中的安全性和耐受性，并评估了其对临床结局的影响。
在 36 个儿科重症监护病房进行了一项 II 期、双盲、多中心、安慰剂对照随机试验，纳入了≤2 岁、有急性低氧性呼吸衰竭的婴儿。需要机械通气且持续低氧血症符合急性肺损伤标准的婴儿被随机分配接受气管内 lucinactant（175mg/kg）或空气安慰剂。如果低氧血症持续存在，初始剂量后 12-24 小时允许进行一次补救治疗。评估气管内 lucinactant 的围剂量耐受性和不良事件。使用方差分析来分析机械通气持续时间。Cochran-Mantel-Haenszel 检验用于分类变量。我们纳入了 165 名急性低氧性呼吸衰竭婴儿（84 名 lucinactant；81 名安慰剂）。除了安慰剂组的呼气末正压较高和潮气量较高外，两组在基线特征方面无显著差异。气管内 lucinactant 治疗组的短暂围剂量心动过缓和呼吸暂停发生率明显更高。两组在其他不良事件或死亡率方面无统计学差异。接受 lucinactant 治疗的婴儿的氧合改善，表现为第二次治疗的发生率较低（67% lucinactant 与 81%安慰剂，p=0.02），从入选到剂量后 48 小时动脉血氧分压与吸入氧分数的比值呈改善趋势（p=0.06）。 lucinactant 并未显著缩短机械通气持续时间（几何最小二乘均值：4.0 天 lucinactant 与 4.5 天安慰剂；p=0.254）。在亚组（n=22）中，急性肺损伤（动脉血氧分压与吸入氧分数比值>200）婴儿的机械通气持续时间明显缩短（最小二乘均值：2.4 天 lucinactant 与 4.3 天安慰剂；p=0.006）。
在接受机械通气的急性低氧性呼吸衰竭婴儿中，气管内 lucinactant 治疗似乎通常是安全的。氧合改善和再次治疗需求显著减少表明，lucinactant 可能改善急性低氧性呼吸衰竭婴儿的肺功能。
