© 2003 American Thoracic Society
Meconium Aspiration SyndromeIs Surfactant Lavage the Answer?Section of Neonatology The Children's Hospital, University of Colorado School of Medicine Denver, Colorado Hypoxemic respiratory failure affects approximately 80,000 newborn infants each year in the United States alone (greater than the number of cases of acute respiratory distress syndrome in adults) (1), at an estimated hospital cost of $4.4 billion (2). Of this group of newborns who suffer hypoxemic respiratory failure, more than one-third are born at or near full-term gestation, and the most common etiology in this group is meconium aspiration syndrome. Despite advances in neonatal intensive care over the last 2 decades, meconium aspiration syndrome remains one of the most vexing clinical conditions to manage and is the most common indication for treatment with extracorporeal membrane oxygenation (3). Aspiration of meconium typically occurs after fetal hypoxic/ischemic stress leading to intestinal peristalsis, meconium contamination of the amniotic fluid, and gasping respirations that draw the noxious meconium-stained fluid deep into the fetal lung. Meconium contamination of amniotic fluid occurs in 10–15% of all pregnancies, and 5–10% of these infants develop meconium aspiration syndrome and respiratory failure (4). The clinical presentation of meconium aspiration syndrome can be quite variable. For example, the chest radiograph may be initially marked by patchy parahilar consolidation associated with aspiration of particulate meconium, but subsequent progression of diffuse parenchymal disease may complicate the clinical course (related to a "secondary" surfactant deficiency or surfactant inactivation) (5, 6). A subset of patients with meconium aspiration syndrome has predominantly airway disease associated with aspiration of particulate meconium. The viscous meconium material within airways often causes check–valve obstruction that allows gas flow during inspiration but obstructs expiratory flow, leading to focal lung overinflation and air leak. In this issue of AJRCCM (pp. 456–463), Dargaville and coworkers (7) report a method to enhance removal of particulate meconium from the airway using bronchoalveolar lavage with a dilute bovine surfactant preparation. After induction of lung injury in 2-week-old piglets through the instillation of a meconium slurry into the lung, they compared the effects of bronchoalveolar lavage with dilute surfactant or a perfluorocarbon emulsion. They found that a 30-ml/kg lavage volume of dilute surfactant was associated with increased meconium removal, improved postlavage lung function, and less lung injury as compared with perflourocarbon emulsion or multiple, smaller aliquots of dilute surfactant. Although these findings are intriguing, the potential benefits of surfactant lavage are limited to enhancing removal of particulate meconium and improving lung compliance by virtue of the surfactant effect on alveolar surface tension. Unfortunately, the clinical syndrome of meconium aspiration is considerably more complicated than that induced by instillation of meconium into the airway of healthy 2-week-old piglets. In the most severe cases of meconium aspiration syndrome in newborns, airway and alveolar dysfunction is accompanied by compromised cardiac performance, causing shock and marked pulmonary vascular abnormalities developed over time in utero, leading to severe pulmonary hypertension. In 1984, Murphy and coworkers demonstrated that infants who died with meconium aspiration syndrome in the first days of life had severely abnormal structural muscularization of the smallest intraacinar arteries associated with clinical evidence of pulmonary hypertension and extrapulmonary right-to-left shunting (8). Survival with meconium aspiration syndrome in the current era of extracorporeal life support, however, is approximately 95%, suggesting that the structural and functional abnormalities of the pulmonary vascular bed that occur in utero may undergo rapid resolution after the fetus is removed from a physiologically hostile environment. Thus, the clinical syndrome of meconium aspiration syndrome can involve multisystem organ failure and severe pulmonary vasoreactivity that increases the risks associated with aggressive lung lavage in the early stages of disease. Indeed, in a small pilot trial using a large volume of dilute KL4-surfactant for bronchoalveolar lavage in newborns with meconium aspiration syndrome, Wiswell and coworkers found no significant advantage in oxygenation in the lavaged group as compared with control subjects (9). However, 20% of the lavaged group had the procedure halted because of marked hypoxemia or systemic hypotension. Moreover, conventional endotracheal administration of a small volume of concentrated surfactant solution may be efficacious in patients with meconium aspiration syndrome and less severe disease. Clinical trials have demonstrated improvement in gas exchange and a reduction in the need for treatment with extracorporeal life support in patients with mild to moderate meconium aspiration syndrome (10, 11). Currently, a reasonable approach to the management of meconium aspiration syndrome might include early use of exogenous surfactant as a small volume bolus in patients with evidence of parenchymal lung disease and without echocardiographic evidence of significant pulmonary hypertension. Inhaled nitric oxide has been firmly established as a safe and effective therapy for newborns with severe hypoxemic respiratory failure and pulmonary hypertension, although the interaction of exogenous surfactant therapy with inhaled nitric oxide has not been rigorously tested in a controlled clinical trial. For patients with meconium aspiration syndrome and diffuse parenchymal disease with lung underinflation, lung recruitment with high-frequency oscillatory ventilation may also play an important role early in the course of the disease (12). Any signs of lung overinflation, however, portend the risk for air leak and should be carefully monitored. In this setting, a rational approach to mechanical ventilation might include a conventional strategy that is more analogous to the management of respiratory failure in asthma, using slow ventilator rates and allowing increased time for expiration. Large-volume lung lavage with dilute surfactant may be quite effective in removing particulate meconium from the lung, but its application in the human newborn with severe meconium aspiration syndrome may also carry substantial risks. Hemodynamic instability and pulmonary hypertension commonly occur in association with meconium aspiration syndrome, and large-volume lung lavage could potentially exacerbate these conditions, causing acute deterioration. In this regard, more carefully characterizing the cardiopulmonary perturbations in meconium aspiration syndrome is an important area for further clinical investigation, and the safety and efficacy of surfactant lavage await the conclusion of the multicenter, randomized trial of KL4-surfactant that is currently underway. Acknowledgments J.P.K. has no declared conflict of interest. REFERENCES
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