Cochrane Review Summary A summary of findings from the Cochrane Library with implications for critical care nursing
Surfactant Therapy for Bronchiolitis in Critically Ill Infants Daphne Stannard, RN, PhD, CCRN, CCNS
Review Question 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?
Relevance to Critical Care Nursing 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.
Contributing Editor 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. ©2013 American Association of Critical-Care Nurses doi: http://dx.doi.org/10.4037/ccn2013893
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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.
Study Description and Results 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.
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Secondary outcomes included the following: • Duration of stay in intensive care unit • Duration of hospital stay • Gas exchange (effects on oxygenation as measured by the ratio of PO2 to fraction of inspired oxygen [FIO2] and carbon dioxide elimination as measured by the PCO2 level) • Respiratory mechanics (as measured by effects on pulmonary compliance and airway resistance) • Recurrent lower respiratory tract disease 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 www.ccnonline.org
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 I 2 statistic. A fixed-effect model was used and statistical analyses were performed by using RevMan 2011 (Cochrane Software).
Summary of Main Results • Mortality data were described for 60 participants in 2 studies. No deaths occurred in either study. • Duration of mechanical ventilation was reported in all 3 studies. Duration of mechanical ventilation was significantly
less in the Italian studies, but there was no significant difference in the UK study. When the data from the 3 studies were pooled, the duration of mechanical ventilation was no different in the surfactant group than in the control group (mean difference, -63.04 hours; 95% CI, -130.43 to 4.35 hours), but there was a trend toward beneficial effects of surfactant. There was statistically significant heterogeneity for duration of mechanical ventilation in 1 of the Italian studies, where blinding was not attempted and controls had comparatively higher duration of mechanical ventilation. After this study was excluded from the meta-analysis, the duration of mechanical ventilation was significantly lower in the surfactant group (mean difference, -28.99 hours; 95% CI, -40.10 to -17.87 hours). • No significant change in heart rate or blood pressure was reported in 2 studies, and no adverse events or complications were noted in any of the studies. • Duration of stay in the intensive care unit was reported in all 3 studies. The UK study had a nonsignificant difference in duration of stay between the intervention and control group. Duration of stay in the intensive care unit for the control group was just significantly less for both Italian studies. After the data were combined, the duration of the stay was significantly less in
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the surfactant group than in the control group (mean difference, -3.31 days; 95% CI, -6.38 to -0.25 days). The significant heterogeneity for duration of stay in the intensive care unit was attributable to the 1 Italian study. After that study was excluded from the analysis, the results were still significant (mean difference, -1.81 days; 95% CI, -2.42 to -1.19 days). • Duration of hospital stay was reported only in the UK study, and it was not significantly different between the groups (13 days vs 17 days; P=.30). • Oxygenation, as measured by the PO2/FIO2 ratio, was reported in the 2 Italian studies. The ratio was significantly higher in the surfactant group at 1, 3, 12, and 24 hours in 1 study and at 1, 3, 6, 12, 24, and 48 hours in the second study. The UK study reported oxygenation as the oxygenation index and alveolar arterial gradient. In that study, the mean oxygenation index and alveolar arterial gradient changed from 6.3 to 9.3 and 198 to 246, respectively, following the first dose of surfactant and changed from 6.8 to 7.6 and 191 to 225 after the second dose. Although these changes may have been clinically significant, they were not statistically significant. After the data from the 2 Italian studies were combined, the PO2/FIO2 ratio at 12 and 24 hours of surfactant administration was significantly higher in the surfactant group (mean difference, 99.08;
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95% CI, 57.43 to 140.72) at 12 hours and (mean difference, 109.64; 95% CI, 63.29 to 155.99) at 24 hours. • A significant reduction in PCO2 was observed in the surfactant group as compared with the control group in both Italian studies: at 12 and 24 hours in the first study and at 1, 3, 6, 12, 24, and 48 hours in the second study. The ventilation index did not significantly change in the UK study after surfactant administration. The pooled carbon dioxide values from the 2 Italian studies were significantly less in the surfactant group at 12 hours (mean difference, 7.63 mm Hg; 95% CI, -8.99 to 6.28 mm Hg) than at 24 hours (mean difference, -7.90 mm Hg; 95% CI, -9.42 to -6.38 mm Hg). • Data regarding lung compliance after surfactant administration were available from 1 Italian study and the UK study. The static compliance was significantly higher in the surfactant group at 1, 3, 6, 12, 24, and 48 hours in the Italian study. In the UK study, compliance decreased in the placebo group at 30 hours after surfactant administration (0.36 to 0.27 mL/cm H2O per kilogram; P
Surfactant Therapy for Bronchiolitis in Critically Ill Infants Daphne Stannard, RN, PhD, CCRN, CCNS
Review Question 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?
Relevance to Critical Care Nursing 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.
Contributing Editor 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. ©2013 American Association of Critical-Care Nurses doi: http://dx.doi.org/10.4037/ccn2013893
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CriticalCareNurse
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.
Study Description and Results 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.
Vol 33, No. 6, DECEMBER 2013
Downloaded from http://ccn.aacnjournals.org/ by guest on June 5, 2015
www.ccnonline.org
Secondary outcomes included the following: • Duration of stay in intensive care unit • Duration of hospital stay • Gas exchange (effects on oxygenation as measured by the ratio of PO2 to fraction of inspired oxygen [FIO2] and carbon dioxide elimination as measured by the PCO2 level) • Respiratory mechanics (as measured by effects on pulmonary compliance and airway resistance) • Recurrent lower respiratory tract disease 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 www.ccnonline.org
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 I 2 statistic. A fixed-effect model was used and statistical analyses were performed by using RevMan 2011 (Cochrane Software).
Summary of Main Results • Mortality data were described for 60 participants in 2 studies. No deaths occurred in either study. • Duration of mechanical ventilation was reported in all 3 studies. Duration of mechanical ventilation was significantly
less in the Italian studies, but there was no significant difference in the UK study. When the data from the 3 studies were pooled, the duration of mechanical ventilation was no different in the surfactant group than in the control group (mean difference, -63.04 hours; 95% CI, -130.43 to 4.35 hours), but there was a trend toward beneficial effects of surfactant. There was statistically significant heterogeneity for duration of mechanical ventilation in 1 of the Italian studies, where blinding was not attempted and controls had comparatively higher duration of mechanical ventilation. After this study was excluded from the meta-analysis, the duration of mechanical ventilation was significantly lower in the surfactant group (mean difference, -28.99 hours; 95% CI, -40.10 to -17.87 hours). • No significant change in heart rate or blood pressure was reported in 2 studies, and no adverse events or complications were noted in any of the studies. • Duration of stay in the intensive care unit was reported in all 3 studies. The UK study had a nonsignificant difference in duration of stay between the intervention and control group. Duration of stay in the intensive care unit for the control group was just significantly less for both Italian studies. After the data were combined, the duration of the stay was significantly less in
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the surfactant group than in the control group (mean difference, -3.31 days; 95% CI, -6.38 to -0.25 days). The significant heterogeneity for duration of stay in the intensive care unit was attributable to the 1 Italian study. After that study was excluded from the analysis, the results were still significant (mean difference, -1.81 days; 95% CI, -2.42 to -1.19 days). • Duration of hospital stay was reported only in the UK study, and it was not significantly different between the groups (13 days vs 17 days; P=.30). • Oxygenation, as measured by the PO2/FIO2 ratio, was reported in the 2 Italian studies. The ratio was significantly higher in the surfactant group at 1, 3, 12, and 24 hours in 1 study and at 1, 3, 6, 12, 24, and 48 hours in the second study. The UK study reported oxygenation as the oxygenation index and alveolar arterial gradient. In that study, the mean oxygenation index and alveolar arterial gradient changed from 6.3 to 9.3 and 198 to 246, respectively, following the first dose of surfactant and changed from 6.8 to 7.6 and 191 to 225 after the second dose. Although these changes may have been clinically significant, they were not statistically significant. After the data from the 2 Italian studies were combined, the PO2/FIO2 ratio at 12 and 24 hours of surfactant administration was significantly higher in the surfactant group (mean difference, 99.08;
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95% CI, 57.43 to 140.72) at 12 hours and (mean difference, 109.64; 95% CI, 63.29 to 155.99) at 24 hours. • A significant reduction in PCO2 was observed in the surfactant group as compared with the control group in both Italian studies: at 12 and 24 hours in the first study and at 1, 3, 6, 12, 24, and 48 hours in the second study. The ventilation index did not significantly change in the UK study after surfactant administration. The pooled carbon dioxide values from the 2 Italian studies were significantly less in the surfactant group at 12 hours (mean difference, 7.63 mm Hg; 95% CI, -8.99 to 6.28 mm Hg) than at 24 hours (mean difference, -7.90 mm Hg; 95% CI, -9.42 to -6.38 mm Hg). • Data regarding lung compliance after surfactant administration were available from 1 Italian study and the UK study. The static compliance was significantly higher in the surfactant group at 1, 3, 6, 12, 24, and 48 hours in the Italian study. In the UK study, compliance decreased in the placebo group at 30 hours after surfactant administration (0.36 to 0.27 mL/cm H2O per kilogram; P
