Heated Humidified High-Flow Nasal Cannula for Preterm Infants: An Updated Systematic Review and Meta-analysis.

BACKGROUND: Heated humidified high-flow nasal cannula (HHHFNC) is gaining popularity as a mode of respiratory support. We updated a systematic review and meta-analyses examining the efficacy and safety of HHHFNC compared with standard treatments for preterm infants. The primary outcome was the need for reintubation for preterm infants following mechanical ventilation (post-extubation analysis) or need for intubation for preterm infants not previously intubated (analysis of primary respiratory support). METHODS: We searched PubMed, MEDLINE, Embase, and the Cochrane Library for randomized controlled trials (RCTs) of HHHFNC versus standard treatments. Meta-analysis was conducted using Review Manager 5.3. RESULTS: The post-extubation analysis included ten RCTs (n = 1,201), and the analysis of primary respiratory support included ten RCTs (n = 1,676). There were no statistically significant differences for outcomes measuring efficacy, including the primary outcome. There were statistically significant differences favoring HHHFNC versus nasal cannula positive airway pressure (NCPAP) for air leak (post-extubation, risk ratio [RR] 0.29, 95 percent confidence interval [CI] 0.11 to 0.76, I2 = 0) and nasal trauma (post-extubation: 0.35, 95 percent CI 0.27 to 0.46, I2 = 5 percent; primary respiratory support: RR 0.52, 95 percent CI 0.37 to 0.74; I2 = 27 percent). Studies, particularly those of primary respiratory support, included very few preterm infants with gestational age (GA) <28 weeks. CONCLUSIONS: HHHFNC may offer an efficacious and safe alternative to NCPAP for some infants but evidence is lacking for preterm infants with GA ≤28 weeks.

The clinical effectiveness and cost-effectiveness of heated humidified high-flow nasal cannula compared with usual care for preterm infants: systematic review and economic evaluation.

BACKGROUND: Respiratory problems are one of the most common causes of morbidity in preterm infants and may be treated with several modalities for respiratory support such as nasal continuous positive airway pressure (NCPAP) or nasal intermittent positive-pressure ventilation. The heated humidified high-flow nasal cannula (HHHFNC) is gaining popularity in clinical practice. OBJECTIVES: To address the clinical effectiveness of HHHFNC compared with usual care for preterm infants we systematically reviewed the evidence of HHHFNC with usual care following ventilation (the primary analysis) and with no prior ventilation (the secondary analysis). The primary outcome was treatment failure defined as the need for reintubation (primary analysis) or intubation (secondary analysis). We also aimed to assess the cost-effectiveness of HHHFNC compared with usual care if evidence permitted. DATA SOURCES: The following databases were searched: MEDLINE (2000 to 12 January 2015), EMBASE (2000 to 12 January 2015), The Cochrane Library (issue 1, 2015), ISI Web of Science (2000 to 12 January 2015), PubMed (1 March 2014 to 12 January 2015) and seven trial and research registers. Bibliographies of retrieved citations were also examined. REVIEW METHODS: Two reviewers independently screened all titles and abstracts to identify potentially relevant studies for inclusion in the review. Full-text copies were assessed independently. Data were extracted and assessed for risk of bias. Summary statistics were extracted for each outcome and, when possible, data were pooled. A meta-analysis was only conducted for the primary analysis, using fixed-effects models. An economic evaluation was planned. RESULTS: Clinical evidence was derived from seven randomised controlled trials (RCTs): four RCTs for the primary analysis and three RCTs for the secondary analysis. Meta-analysis found that only for nasal trauma leading to a change of treatment was there a statistically significant difference, favouring HHHFNC over NCPAP [risk ratio (RR) 0.21, 95% confidence interval (CI) 0.10 to 0.42]. For the following outcomes, there were no statistically significant differences between arms: treatment failure (reintubation < 7 days; RR 0.76, 95% CI 0.54 to 1.09), bronchopulmonary dysplasia (RR 0.92, 95% CI 0.72 to 1.17), death (RR 0.56, 95% CI 0.22 to 1.44), pneumothorax (RR 0.33, 95% CI 0.03 to 3.12), intraventricular haemorrhage (grade ≥ 3; RR 0.41, 95% CI 0.15 to 1.15), necrotising enterocolitis (RR 0.41, 95% CI 0.15 to 1.14), apnoea (RR 1.08, 95% CI 0.74 to 1.57) and acidosis (RR 1.16, 95% CI 0.38 to 3.58). With no evidence to support the superiority of HHHFNC over NCPAP, a cost-minimisation analysis was undertaken, the results suggesting HHHFNC to be less costly than NCPAP. However, this finding is sensitive to the lifespan of equipment and the cost differential of consumables. LIMITATIONS: There is a lack of published RCTs of relatively large-sized populations comparing HHHFNC with usual care; this is particularly true for preterm infants who had received no prior ventilation. CONCLUSIONS: There is a lack of convincing evidence suggesting that HHHFNC is superior or inferior to usual care, in particular NCPAP. There is also uncertainty regarding whether or not HHHFNC can be considered cost-effective. Further evidence comparing HHHFNC with usual care is required. STUDY REGISTRATION: This review is registered as PROSPERO CRD42015015978. FUNDING: The National Institute for Health Research Health Technology Assessment programme.

WITHDRAWN. Inhaled steroids for neonatal chronic lung disease.

BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic disorder associated with prematurity. Systemic steroids induce at least a temporary improvement in respiratory function, but are associated with adverse side effects. Inhaled steroids have fewer side effects. OBJECTIVES: To determine if inhaled corticosteroids are effective in alleviating the morbidity of bronchopulmonary dysplasia (BPD) compared to placebo. SEARCH STRATEGY: We identified randomised, controlled trials (RCT) within the Cochrane Database, references from retrieved trials, hand searches of journals and contact with pharmaceutical companies and experts in this field. SELECTION CRITERIA: Only randomised controlled trials involving infants with chronic lung disease of prematurity and treated with inhaled steroids versus placebo were included. Patients receiving systemic corticosteroids were excluded. Co-interventions included antenatal systemic steroids, routine neonatal intensive care, ventilatory support, surfactant replacement therapy, diuretics and bronchodilators. DATA COLLECTION AND ANALYSIS: Four of the seven included trials were of good methodological quality. There were five parallel-group trials in ventilated infants. These were comparable in terms of population, co-interventions and need for increased inspired oxygen concentration. They differed in terms of type, dose and duration (7-28 days) of inhaled steroids. Two cross-over trials were performed in non-ventilated patients. An update search was conducted in June 2002, which identified an additional excluded study. MAIN RESULTS: The inability to extubate during treatment was markedly reduced in infants treated with inhaled steroids; Peto Odds Ratio (OR) 0.12, 95% Confidence Interval (CI) 0.03 to 0.43. There was heterogeneity in this finding, however, with one study that contributed 30% of the total number of patients reporting no successful extubations in either treatment arm over one week. The risk of sepsis appeared similar between the two groups (N=3, OR=0.72, 95%CI: 0.21 to 2.43). The small number of trials precluded analysis to examine the effect of differences in drug, duration of therapy, delivery system, co-interventions, and disease severity. Reduced oxygen requirements were reported in one of the two trials performed in non-ventilated infants, but inadequate data reporting precluded pooling of data. AUTHORS' CONCLUSIONS: In ventilated infants with BPD, inhaled steroids administered for 1 to 4 weeks improved the rate of extubation with no apparent increase in the risk of sepsis. No firm conclusion could be derived with regard to the efficacy of inhaled steroids in non-ventilated infants.