Surfactant Therapy for Bronchiolitis in Critically Ill Infants

Abstract

Daphne Stannard, the contributing editor for the Cochrane Review Summary, is the chief nurse researcher and director of the Institute for Nursing Excellence at UCSF Medical Center, San Francisco, California. She is also the director of the UCSF JBI Centre.For questions related to this article, contact Daphne Stannard at daphne.stannard@ucsfmedctr.org.How effective is exogenous surfactant administration (ie, intratracheal administration of surfactant of any type, at any dose, and at any time after start of mechanical ventilation) compared with placebo, no intervention, or standard care in reducing mortality and duration of ventilation in infants and children with bronchiolitis requiring mechanical ventilation?Pulmonary surfactant is an endogenous phospholipid compound that is synthesized and secreted by type II alveolar cells. Surfactant greatly reduces surface tension within the alveoli, helping to prevent alveolar collapse. Additionally, low surface tension at the alveolar level increases overall compliance of the lung and reduces the work of breathing. Surfactant is formed late in fetal life, and babies born without adequate amounts often have significant morbidity and mortality.1 Two types of exogenous surfactants are available for clinical use: animal (porcine and bovine) and synthetic. Use of exogenous surfactants in preterm babies with respiratory distress syndrome/hyaline membrane disease has been extensively studied and is now considered the standard treatment for this condition.Surfactant abnormalities have been observed in severe cases of bronchiolitis or inflammation of the small airways in the lung.2 Although bronchiolitis is a frequent cause of respiratory failure in infants and children, there is no effective therapy available except for supportive care (which includes adequate fluid intake, antipyretics, and oxygen supplementation as needed). While many therapeutic interventions other than supportive care have been used to treat bronchiolitis, including exogenous surfactant administration, their effectiveness is not well documented.This summary is based on a Cochrane systematic review containing 3 small randomized controlled trials, which included a total of 79 participants. Primary outcomes included mortality, duration of mechanical ventilation in hours, and adverse effects. For the purposes of this review, adverse effects included desaturation, change in heart rate and/or blood pressure, bronchospasm, and other complications such as pneumothorax. Secondary outcomes included the following:Two of the studies were from Italy, and one was from the United Kingdom (UK). One of the Italian studies was a multicenter trial that included 6 centers. The age of the included participants ranged from 1 week to 2.5 years in the Italian studies and a median age of 2 months in the surfactant group and 1.4 months in the control group in the UK study. No major difference in distribution of the sexes was apparent among the studies, with 40 males and 39 females.Most participants had respiratory syncytial virus–induced respiratory failure except for in 1 Italian study, where the viral origin was known only in 20% of the cases (n=20) and these cases were positive for respiratory syncytial virus. This same study enrolled patients when they were receiving mechanical ventilation for 24 hours without significant clinical improvement, and porcine surfactant was used 50 mg/kg in 2 to 3 doses. The multicenter Italian study included participants who were receiving mechanical ventilation for at least 12 hours without significant improvement, and porcine surfactant was used 50 mg/kg in 2 aliquots over 5 minutes. The UK study enrolled participants who had been receiving mechanical ventilation for less than 24 hours, and bovine surfactant was administered in 2 doses (100 mg/kg) 24 hours apart. The exogenous surfactant was administered through an endotracheal tube in all studies. The Italian studies used no placebo in the control arms, and the UK study used an air placebo.Participants with uncorrected congenital heart disease and neuromuscular diseases were excluded in 2 studies. The Italian multicenter study also excluded children with chronic lung disease, whereas the UK study did not exclude children with chronic lung disease or a history of prematurity. The risk of bias was unclear in some of the included studies, but none of the included studies had a high risk of bias.Dichotomous outcomes were analyzed by calculating the risk ratio and risk difference. Continuous outcomes were analyzed as mean differences. The overall results were expressed with 95% confidence intervals (CIs). Both clinical and methodological heterogeneity was assessed before pooling by using the χ2 test and the I2 statistic. A fixed-effect model was used and statistical analyses were performed by using RevMan 2011 (Cochrane Software).The available evidence is insufficient to establish the effectiveness of surfactant therapy for bronchiolitis in critically ill infants who require mechanical ventilation. Larger trials with adequate power to evaluate the effectiveness of exogenous surfactant therapy for infants with bronchiolitis who require intensive care are needed.3