• Brigitte Lemyre, Peter G Davis, Antonio G De Paoli, and Haresh Kirpalani.
• Division of Neonatology, Children's Hospital of Eastern Ontario, 401 Smyth Road, Ottawa, ON, Canada, KlH 8L1.
• Cochrane Db Syst Rev. 2014 Jan 1;9:CD003212.

BackgroundPrevious randomised trials and meta-analyses have shown nasal continuous positive airway pressure (NCPAP) to be a useful method of respiratory support after extubation. However, infants managed in this way sometimes 'fail' and require endotracheal reintubation with its attendant risks and expense. Nasal intermittent positive pressure ventilation (NIPPV) is a method of augmenting NCPAP by delivering ventilator breaths via nasal prongs. Older children and adults with chronic respiratory failure benefit from NIPPV and the technique has been applied to neonates. However, serious side effects including gastric perforation have been reported with older techniques to provide NIPPV.ObjectivesTo determine the effect of management with NIPPV compared with NCPAP on the need for additional ventilatory support in preterm infants having their endotracheal tube removed following a period of intermittent positive pressure ventilation.To compare the rates of gastric distension, gastrointestinal perforation, necrotising enterocolitis, chronic lung disease, duration of hospitalisation, rates of apnoea, air leaks and mortality between NIPPV and NCPAP.Search MethodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 7, 2013), MEDLINE (1966 to 4 September 2013), EMBASE (1980 to 4 September 2013), CINAHL (1982 week 3 to August 2013) and PubMed (4 September 2013). We searched previous reviews including cross-references, and conference and symposia proceedings. We contacted experts in the field. We also searched Clinicaltrials.gov for any ongoing trials.Selection CriteriaWe included randomised and quasi-randomised trials comparing the use of NIPPV with NCPAP in preterm infants being extubated. NIPPV included non-invasive support delivered by a mechanical ventilator or a bilevel device in a synchronised or non-synchronised way. Participants included ventilated preterm infants who were ready to be extubated to non-invasive respiratory support. Interventions compared were NIPPV, either by short nasal prongs or nasopharyngeal tube, and NCPAP, delivered by the same methods.Types of outcomes measures included: failure of therapy (respiratory failure, rates of endotracheal reintubations); gastrointestinal complications (i.e. abdominal distension requiring cessation of feeds, gastrointestinal perforation or necrotising enterocolitis); pulmonary air leaks; chronic lung disease (oxygen requirement at 36 weeks' postmenstrual age) and mortality.Data Collection And AnalysisThree review authors independently extracted data regarding clinical outcomes including extubation failure, endotracheal reintubation, rates of apnoea, gastrointestinal perforation, feeding intolerance, necrotising enterocolitis, chronic lung disease, air leaks and duration of hospital stay. We analysed the trials using risk ratio (RR), risk difference (RD) and number needed to treat for an additional beneficial outcome (NNTB) or additional harmful outcome (NNTH) for dichotomous outcomes and mean difference (MD) for continuous outcomes.Main ResultsThe search identified eight trials enrolling 1316 infants in total and comparing extubation of infants to NIPPV or NCPAP. Five trials used the synchronised form of NIPPV, two trials used the non-synchronised form and one trial used both methods. Six studies used NIPPV delivered by a ventilator, one study used a bilevel device and one study used both methods. When all studies were included, the meta-analysis demonstrated a statistically and clinically significant reduction in the risk of meeting extubation failure criteria (typical RR 0.71, 95% CI 0.61 to 0.82; typical RD -0.12, 95% CI -0.17 to -0.07; NNTB 8, 95% CI 6 to 14; 8 trials, 1301 infants) and needing reintubation (typical RR 0.76, 95% CI 0.65 to 0.88; typical RD -0.10, 95% CI -0.15 to -0.05; NNTB 10, 95% CI 7 to 20; 8 trials, 1301 infants). While the method of synchronisation varied (Graseby capsule or pneumotachograph/flow-trigger), the five trials that synchronised NIPPV showed a statistically significant benefit for infants extubated to NIPPV in terms of prevention of extubation failure up to one week after extubation. NIPPV provided via a ventilator appeared more beneficial than bilevel devices in reducing extubation failure in the first week. There was no significant reduction in the rates of chronic lung disease (typical RR 0.97, 95% CI 0.83 to 1.14; typical RD -0.01, 95% CI -0.07 to 0.05), death or difference in the incidence of necrotising enterocolitis between interventions. There was a reduction in air leaks in infants randomised to NIPPV (typical RR 0.50, 95% CI 0.28 to 0.89; typical RD -0.03; 95% CI -0.05 to -0.01; NNTB 33, 95% CI 20 to 100).Authors' ConclusionsImplications For PracticeNIPPV reduces the incidence of symptoms of extubation failure and need for reintubation within 48 hours to one week more effectively than NCPAP; however, it has no effect on chronic lung disease or mortality. Synchronisation may be important in delivering effective NIPPV. The device used to deliver NIPPV may also be important; however, there are insufficient data to support strong conclusions. NIPPV does not appear to be associated with increased gastrointestinal side effects.Implications For Researchthe impact of synchronisation of NIPPV on the technique's safety and efficacy should be established in large trials. The efficacy of bilevel devices should be compared with NIPPV provided by a ventilator in trials. The best combination of settings for NIPPV needs to be established in future trials.

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