Multicenter, randomized, controlled study of porcine surfactant in severe respiratory syncytial virus-induced respiratory failure. Exogenous surfactant supplementation in infants with respiratory syncytial virus bronchiolitis. Porcine-derived surfactant treatment of severe bronchiolitis.
OBJECTIVE: Recently, natural exogenous surfactant replacement has been used in experimental models and clinical trials for the treatment of severe respiratory syncytial virus (RSV) disease. The present study was aimed at verifying this hypothesis and confirming the results of our previous pilot study by assessing the effect of surfactant treatment in mechanically ventilated infants with severe RSV-induced respiratory failure. DESIGN: Multicenter, randomized, controlled study. SETTING: Six pediatric intensive care units staffed by full-time intensive care physicians. PATIENTS: A total of 40 infants (20 treated and 20 controls) with RSV-induced respiratory failure requiring conventional mechanical ventilation (CMV) were randomly assigned to either exogenous surfactant (treated group) or conventional treatment (control group) over a 1-yr period. INTERVENTIONS: Fifty milligrams per kilogram of body weight of porcine-derived natural surfactant (Curosurf) was administered. The drug was instilled by means of a syringe attached to a small suction catheter inserted into the endotracheal tube down to its tip, momentarily disconnecting the patient from CMV. Main Outcome Measures: The assessment consisted of the following outcome variables: duration of CMV, length of intensive care unit stay, gas exchange, respiratory mechanics, re-treatment need, complications, and mortality. RESULTS: The two groups were similar with regard to demographics, Pediatric Risk of Mortality scores, and baseline Pao(2)/Fio(2), Paco(2), and ventilator settings. A marked increase in Pao(2)/Fio(2) and decrease in Paco(2) were observed in the treated group after surfactant administration. Hemodynamic parameters remained unchanged throughout the study period. Peak inspiratory pressure and static compliance were similar at baseline in the two groups. A decrease in peak inspiratory pressure and increase in static compliance were observed in the treated group after surfactant administration. Among surfactant-treated patients, 15 received the treatment within 24 hrs of admission, whereas the remainder (five patients) were treated later. Among children who were treated later, three needed an additional dose of surfactant. None of the children treated within 24 hrs needed an additional dose. Duration of CMV and length of stay in the intensive care unit were significantly shorter in the treated group (4.6 +/- 0.8 and 6.4 +/- 0.9 days, respectively) compared with the control group (5.8 +/- 0.7 and 8.2 +/- 1.1 days, respectively) (p <.0001). No relevant complications were observed, and all the infants survived. CONCLUSIONS: Consistent with our previous study and others, this study shows that surfactant therapy improves gas exchange and respiratory mechanics and shortens CMV and intensive care unit stay in infants with severe RSV-induced respiratory failure. Infants with respiratory syncytial virus (RSV) bronchiolitis are deficient in surfactant, both in quantity and ability to reduce surface tension. New evidence suggests surfactant has a role in maintaining the patency of conducting airways, which has implications for RSV bronchiolitis. A randomized, controlled pilot study was undertaken to assess the effects of exogenous surfactant supplementation to RSV-positive infants on pulmonary mechanics, indices of gas exchange, and the phospholipid composition of bronchoalveolar lavage fluid (BALF). Nineteen ventilated infants (median corrected age 4 wk) received either two doses of surfactant (Survanta, 100 mg/kg) within 24 and 48 h of mechanical ventilation (n = 9), or air placebo (n = 10). Static lung compliance and resistance of infants in the placebo but not in the surfactant-treated group became progressively worse over the first 30 h following enrollment. Although no significant acute changes in gas exchange parameters were seen following surfactant, infants in the surfactant group showed a more rapid improvement in oxygenation and ventilation indices over the first 60 h of ventilation. Surfactant status was assessed from the concentration ratio in BALF of the disaturated phospholipid species dipalmitoylphosphatidylcholine to that of the monounsaturated species palmitoyloleoylphosphatidylcholine. This ratio correlated with both lung compliance (positively) and resistance (negatively), and over time increased in the treated group and declined in placebo infants. The data from this pilot study suggest that functional surfactant has a role in maintaining small airway patency as well as lung compliance in infants infected with RSV and an outcome study is now warranted. It is hypothesized that surfactant treatment helps to improve severe bronchiolitis by restoring surfactant system activity. This study aims to assess the effect of surfactant on gas exchange, peak inspiratory pressure and duration of mechanical ventilation and intensive care unit (ICU) stay in children with severe bronchiolitis.
                Twenty children with bronchiolitis requiring mechanical ventilation were randomly assigned to one of two groups (10 patients each). Group A was treated with continuous positive pressure ventilation (CPPV) plus surfactant. Group B was treated with CPPV only. Porcine-derived surfactant, 50 mg/kg body weight, was instilled into the trachea. Arterial tension of oxygen/fraction of inspired oxygen (PaO2/FiO2) ratio, arterial tension of carbon dioxide (PaCO2), and peak inspiratory pressure (PIP) were assessed. Heart rate and non-invasive arterial blood pressure were monitored. The duration of CPPV and the length of ICU stay were also recorded. Finally, the incidence of complications and the survival rate were assessed.
                In group A, the PaO2/FiO2 ratio significantly improved from 1 h and a reduction in PaCO2 was noted from 12 h. A reduction of PIP was observed from 3 h. The duration of CPPV and the length of ICU stay were reduced in group A. No complications were reported in either group and all children survived.
                Surfactant treatment of severe bronchiolitis appeared to improve gas exchange, reduce PIP and shorten CPPV and ICU stay. However, these initial results must be confirmed by a larger and more rigorously controlled study.
The available evidence is insufficient to establish the effectiveness of surfactant therapy for bronchiolitis in critically ill infants who require mechanical ventilation. There is a need for larger trials with adequate power and a cost-effectiveness analysis to evaluate the effectiveness of exogenous surfactant therapy for infants with bronchiolitis who require intensive care management.