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Surfactant Therapy for Bronchiolitis in Critically Ill Infants (Review)

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Surfactant Therapy for Bronchiolitis in Critically Ill Infants (Review) Surfactant therapy for bronchiolitis in critically ill infants (Review) Jat KR, Chawla D This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library 2012, Issue 9 http://www.thecochranelibrary.com Surfactant therapy for bronchiolitis in critically ill infants (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 PLAINLANGUAGESUMMARY . 2 SUMMARY OF FINDINGS FOR THE MAIN COMPARISON . ..... 2 BACKGROUND .................................... 5 OBJECTIVES ..................................... 6 METHODS ...................................... 6 Figure1. ..................................... 8 Figure2. ..................................... 9 RESULTS....................................... 10 Figure3. ..................................... 12 Figure4. ..................................... 13 Figure5. ..................................... 14 Figure6. ..................................... 14 Figure7. ..................................... 15 DISCUSSION ..................................... 15 AUTHORS’CONCLUSIONS . 17 ACKNOWLEDGEMENTS . 17 REFERENCES ..................................... 17 CHARACTERISTICSOFSTUDIES . 20 DATAANDANALYSES. 25 Analysis 1.1. Comparison 1 Primary outcomes, Outcome 1 Mortality. ................ 25 Analysis 1.2. Comparison 1 Primary outcomes, Outcome 2 Duration of mechanical ventilation (hours). 26 Analysis 2.1. Comparison 2 Secondary outcomes, Outcome 1 Duration of ICU stay (days). 27 Analysis 2.2. Comparison 2 Secondary outcomes, Outcome 2 Po2/Fio2 ratio at 12 hrs. 27 Analysis 2.3. Comparison 2 Secondary outcomes, Outcome 3 Po2/Fio2 ratio at 24 hrs. 28 Analysis 2.4. Comparison 2 Secondary outcomes, Outcome 4 pCO2 at12hrs(mmHg). 29 Analysis 2.5. Comparison 2 Secondary outcomes, Outcome 5 pCO2 at24hrs(mmHg). 29 APPENDICES ..................................... 29 HISTORY....................................... 33 CONTRIBUTIONSOFAUTHORS . 34 DECLARATIONSOFINTEREST . 34 NOTES........................................ 34 INDEXTERMS .................................... 34 Surfactant therapy for bronchiolitis in critically ill infants (Review) i Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Review] Surfactant therapy for bronchiolitis in critically ill infants Kana R Jat1, Deepak Chawla1 1Department of Pediatrics, Government Medical College and Hospital, Chandigarh, India Contact address: Kana R Jat, Department of Pediatrics, Government Medical College and Hospital, Sector-32, Chandigarh, Chandigarh UT, 160030, India. [email protected]. [email protected]. Editorial group: Cochrane Acute Respiratory Infections Group. Publication status and date: New, published in Issue 9, 2012. Review content assessed as up-to-date: 11 May 2012. Citation: Jat KR, Chawla D. Surfactant therapy for bronchiolitis in critically ill infants. Cochrane Database of Systematic Reviews 2012, Issue 9. Art. No.: CD009194. DOI: 10.1002/14651858.CD009194.pub2. Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT Background Bronchiolitis is one of the most frequent causes of respiratory failure in infants; some infants will require intensive care and mechanical ventilation. There is lack of evidence regarding effective treatment for bronchiolitis other than supportive care. Abnormalities of surfactant quantity or quality (or both) have been observed in severe cases of bronchiolitis. Exogenous surfactant administration appears to favourably change the haemodynamics of the lungs and may be a potentially promising therapy for severe bronchiolitis. Objectives To evaluate the efficacy of exogenous surfactant administration (i.e. intratracheal administration of surfactant of any type (whether animal-derived or synthetic), at any dose and at any time after start of ventilation) compared to placebo, no intervention or standard care in reducing mortality and the duration of ventilation in infants and children with bronchiolitis requiring mechanical ventilation. Search methods We searched CENTRAL 2012, Issue 4 which contains the Cochrane Acute Respiratory Infections Group’s Specialised Register, MEDLINE (1948 to May week 1, 2012), EMBASE (1974 to May 2012), CINAHL (1982 to May 2012), LILACS (1985 to May 2012) and Web of Science (1985 to May 2012). Selection criteria We considered prospective, randomised controlled trials (RCTs) and quasi-RCTs evaluating the effect of exogenous surfactant in infants and children with bronchiolitis requiring mechanical ventilation. Data collection and analysis Two review authors selected studies independently. We extracted the data using a predefined proforma, independently analysed the data and performed meta-analyses. Main results We included three small RCTs enrolling 79 participants. Two trials did not use a placebo in the control arms and the third trial used air placebo. Two included studies did not describe mortality. We judged some of the included studies to have an unclear risk of bias but none of the included studies had a high risk of bias. Our pooled analysis of the three trials revealed that duration of mechanical ventilation was not different between the groups (mean difference (MD) -63.04, 95% confidence interval (CI) -130.43 to 4.35 hours) but duration of intensive care unit (ICU) stay was less in the surfactant group compared to the control group: MD -3.31 (95% CI Surfactant therapy for bronchiolitis in critically ill infants (Review) 1 Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. -6.38 to -0.25 days). After excluding one trial which produced significant heterogeneity, the duration of mechanical ventilation and duration of ICU stay were significantly lower in the surfactant group compared to the control group: MD -28.99 (95% CI -40.10 to - 17.87 hours) and MD -1.81 (95% CI -2.42 to -1.19 days), respectively. Use of surfactant had favourable effects on oxygenation and CO2 elimination. No adverse effects and no complications were observed in any of the three included studies. Authors’ conclusions 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. PLAIN LANGUAGE SUMMARY Usefulness of surfactant for bronchiolitis in seriously ill infants and children Bronchiolitis is one of the most common causes of respiratory failure in infants. There are no established treatment options for bronchiolitis. Surfactant may be useful in bronchiolitis because of its favourable effect on lung mechanics. Three small randomised controlled trials (RCTs) enrolling 79 participants suggested that the use of surfactant for critically ill infants and children with bronchiolitis may decrease the duration of mechanical ventilation and duration of intensive care unit stay without any side effects. The limited number of studies with small numbers of participants were the limitations of this review. No adverse effects and no complications were observed in the treatment group or control group of any of the three included studies. There is a need for larger trials to establish such benefits of surfactant for bronchiolitis in critically ill infants and children. Surfactant therapy for bronchiolitis in critically ill infants (Review) 2 Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Copyright © 2012 The CochraneSurfactant Collaboration. therapy Published for by bronchiolitis J in critically ill inf SUMMARY OF FINDINGS FOR THE MAIN COMPARISON [Explanation] Surfactant for critically ill infants with bronchiolitis Patient or population: critically ill infants with bronchiolitis Settings: intensive care unit Intervention: surfactant Outcomes Illustrative comparative risks* (95% CI) Relative effect No of participants Quality of the evidence Comments (95% CI) (studies) (GRADE) Assumed risk Corresponding risk ants (Review) Control Surfactant Duration of mechanical The mean duration of The mean duration of 79 ⊕⊕⊕ Duration of mechani- ohn Wiley & Sons, Ltd. ventilation (hours) mechanical ventilation mechanical ventilation (3 studies) moderate2 cal ventilation was high- (hours) in the control (hours) in the interven- est among controls in groups was 170 to 213.6 tion groups was 63.04 Luchetti 1998 where 1 lower (130.43 lower to 4. blinding was not men- 35 higher) tioned Duration of ICU stay The mean duration of ICU The mean duration of ICU 79 ⊕⊕⊕ Duration of ICU stay was (days) stay (days) in the control stay (days) in the inter- (3 studies) moderate2 highest among controls group was 8.2 to 15.7 vention groups was 3. in Luchetti 1998 where days1 31 lower (6.38 to 0.25 blinding was not men- lower) tioned PO2/FiO2 ratio at 12 The mean PO2/FiO2 ratio The mean PO2/FiO2 ratio 60 ⊕⊕⊕ SD was not available for hours at 12 hours in the control at 12 hours in the inter- (2 studies) moderate2 Luchetti 2002; it was group was 140 to 148.1 vention groups was 99. imported from Luchetti 3 08 higher 1998 (57.43 to 140.72 higher) 3 Copyright © 2012 The CochraneSurfactant Collaboration. therapy Published for by bronchiolitis J in critically ill inf PO2/FiO2 ratio at 24
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