Department of Paediatrics, Royal Hobart Hospital, University of Tasmania and Neonatal Respiratory Group, Menzies Research Institute Tasmania, Hobart, Tas, Australia.
Neonatology. 2012;101(4):326-36. doi: 10.1159/000337346. Epub 2012 Jun 1.
Innovation in the field of exogenous surfactant therapy continues more than two decades after the drug became commercially available. One such innovation, lung lavage using dilute surfactant, has been investigated in both laboratory and clinical settings as a treatment for meconium aspiration syndrome (MAS). Studies in animal models of MAS have affirmed that dilute surfactant lavage can remove meconium from the lung, with resultant improvement in lung function. In human infants both non-randomised studies and two randomised controlled trials have demonstrated a potential benefit of dilute surfactant lavage over standard care. The largest clinical trial, performed by our research group in infants with severe MAS, found that lung lavage using two 15-ml/kg aliquots of dilute surfactant did not reduce the duration of respiratory support, but did appear to reduce the composite outcome of death or need for extracorporeal membrane oxygenation. A further trial of lavage therapy is planned to more precisely define the effect on survival. Innovative approaches to surfactant therapy have also extended to the preterm infant, for whom the more widespread use of continuous positive airway pressure (CPAP) has meant delaying or avoiding administration of surfactant. In an effort to circumvent this problem, less invasive techniques of bolus surfactant therapy have been trialled, including instillation directly into the pharynx, via laryngeal mask and via brief tracheal catheterisation. In a recent clinical trial, instillation of surfactant into the trachea using a flexible feeding tube was found to reduce the need for subsequent intubation. We have developed an alternative method of brief tracheal catheterisation in which surfactant is delivered via a semi-rigid vascular catheter inserted through the vocal cords under direct vision. In studies to date, this technique has been relatively easy to perform, and resulted in rapid improvement in lung function and reduced need for subsequent ventilation and duration of oxygen therapy. We are now commencing large-scale clinical trials of this method in preterm infants on CPAP.
外源性表面活性剂治疗领域的创新已经持续了二十多年,自从该药物商业化以来。其中一项创新,即用稀释的表面活性剂进行肺灌洗,已经在实验室和临床环境中作为治疗胎粪吸入综合征 (MAS) 的方法进行了研究。MAS 动物模型的研究证实,稀释的表面活性剂灌洗可以清除肺部的胎粪,从而改善肺功能。在人类婴儿中,非随机研究和两项随机对照试验都表明,稀释的表面活性剂灌洗比标准治疗有潜在的益处。我们的研究小组在患有严重 MAS 的婴儿中进行的最大规模临床试验发现,使用两剂 15ml/kg 的稀释表面活性剂进行肺灌洗并没有减少呼吸支持的时间,但似乎确实降低了死亡或需要体外膜氧合的复合结局。计划进行进一步的灌洗治疗试验,以更准确地确定对生存的影响。表面活性剂治疗的创新方法也扩展到了早产儿,由于更广泛地使用持续气道正压通气 (CPAP),这意味着延迟或避免给予表面活性剂。为了解决这个问题,人们尝试了更具侵入性的表面活性剂推注治疗技术,包括直接注入咽部、通过喉罩和通过短暂的气管导管。在最近的一项临床试验中,发现通过柔性喂养管将表面活性剂注入气管可以减少随后需要插管的需求。我们开发了一种替代的短暂气管导管插入方法,其中表面活性剂通过插入声带下的半刚性血管导管输送。在迄今为止的研究中,这项技术相对容易实施,并且导致肺功能迅速改善,随后需要通气和吸氧时间减少。我们现在正在开始对 CPAP 治疗的早产儿进行这项技术的大规模临床试验。