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.
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.



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.



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.



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.



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.



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.



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.



This review is registered as PROSPERO CRD42015015978.



The National Institute for Health Research Health Technology Assessment programme.
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Nigel
N
Fleeman
Coldingham Analytical Services, Berwickshire, UK.
James
J
Mahon
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Vickie
V
Bates
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Rumona
R
Dickson
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Yenal
Y
Dundar
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.|Cochrane Editorial Unit, Cochrane Collaboration, London, UK.
Kerry
K
Dwan
Patient representative (parent of premature infants).
Laura
L
Ellis
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Eleanor
E
Kotas
Liverpool Reviews and Implementation Group, University of Liverpool, Liverpool, UK.
Marty
M
Richardson
Departments of Paediatrics and Institute of Health Policy, Management and Evaluation, University of Toronto, Mount Sinai Hospital, Toronto, ON, Canada.
Prakesh
P
Shah
Neonatal Unit, Liverpool Women's NHS Foundation Trust, Liverpool, UK.
Ben Nj
BNj
Shaw
D000072601:Cannula; D002406:Catheterization, Peripheral / Q000295:instrumentation* / Q000379:methods; D045422:Continuous Positive Airway Pressure / Q000379:methods*; D003362:Cost-Benefit Analysis; D006358:Hot Temperature / Q000627:therapeutic use*; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D016032:Randomized Controlled Trials as Topic; D012127:Respiratory Distress Syndrome, Newborn / Q000628:therapy; D013673:Technology Assessment, Biomedical; D016896:Treatment Outcome