Lung lavage with dilute surfactant for meconium aspiration syndrome: a randomized trial

The therapy for meconium aspiration syndrome (MAS) is essentially supportive. The use of innovative therapies such as high frequency oscillatory ventilation and inhaled nitric oxide did not result in a reduction of the duration of ventilation or oxygen therapy. Bolus surfactant therapy for MAS has little effect on mortality, risk of pneumothorax, or duration of intubation, but reduces the need for extracorporeal membrane oxygenation (ECMO). However, none of the supportive therapies currently applied in MAS has the capability to interrupt the sequence of pathophysiological disturbances that occur after aspiration of meconium, including airway obstruction, alveolar inflammation, and surfactant inhibition.
Previous findings, retrieved from experimental and clinical studies, suggested that therapeutic lung lavage with dilute surfactant may alter the course of disease by removing some of the inhaled meconium from the air spaces. Meconium recovery appears optimized with a total lavage fluid volume of 30 mL/kg and an aliquot volume of 15 mL/kg, with open suction and chest squeezing.
On these bases, the international lessMAS Trial Study Group has conducted a randomized controlled trial to evaluate the efficacy of lung lavage and to assess the potential effect of this strategy on the duration of respiratory support, oxygen therapy, and/or hospitalization. Ventilated infants with MAS were randomized to receive lung lavage with two 15-mL/kg aliquots of dilute surfactant or no lavage (control group). The lavage fluid was a 1:5 dilution of surfactant in saline (final concentration 5mg/ml). Control subjects received standard care, which in both groups included high frequency ventilation, nitric oxide, and ECMO, where available.
In total, 66 infants were randomized. Median duration of respiratory support was similar in infants who underwent lavage and control subjects (5.5 vs 6.0 days). Similarly, requirement for high frequency ventilation and nitric oxide did not differ between the groups. Post-hoc analysis showed that fewer infants who underwent lavage died or required ECMO: 10% (3/30) compared with 31% (11/35) in the control group (odds ratio, 0.24; 95% confidence interval, 0.060-0.97). Lavage transiently reduced oxygen saturation without substantial heart rate or blood pressure alterations.
Mean airway pressure was more rapidly weaned in the lavage group after randomization.
In conclusion, this randomized study demonstrated that dilute surfactant lavage is achievable in ventilated infants with severe MAS and a high risk of mortality. Although this strategy does not appear to alter the duration of respiratory support, it may produce a reduction in mortality, especially in units not offering ECMO. However, it must be acknowledged that the uncertainties related to the relatively small number of recruits preclude a definitive recommendation to adopt lavage therapy in such infants. Further trials enrolling a larger number of infants would help to more precisely define the effect on survival.

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