Nasal intermittent positive pressure ventilation (NIPPV) versus nasal continuous positive airway pressure (NCPAP) for preterm neonates after extubation

Key messages

– Compared to NCPAP, NIPPV likely reduces the risk of respiratory failure after extubation and reintubation.

– Compared to NCPAP, NIPPV may reduce leaks of air from the air spaces in the lungs.

Review question

Does nasal intermittent positive pressure ventilation (NIPPV) have short-term and long-term benefits without causing harm to premature infants when coming off a ventilator? How does it compare with nasal continuous positive airway pressure (NCPAP)?

What are NIPPV and NCPAP and why are they needed?

Babies born before their due date (preterm) may have difficulty with spontaneous, unassisted breathing and need respiratory support. Evidence suggests that support using NIPPV increases the effectiveness of NCPAP in preterm babies who no longer need an endotracheal tube (breathing tube in the windpipe). Preterm babies with breathing problems often require help from a machine (ventilator) that provides regular breaths through an endotracheal tube. The process of removal (extubation) of this tube does not always go smoothly, and the tube may need to be reinserted if the baby cannot manage without assistance. NCPAP and NIPPV are ways of supporting babies' breathing in a minimally invasive way as the tubes are short and reach only to the back of the nose, thus causing minimal damage to the lungs. NCPAP and NIPPV may be used after extubation to reduce the number of babies who need reinsertion of the endotracheal tube. NCPAP provides steady pressure to the back of the nose that is transmitted to the lungs, helping the baby breathe more comfortably. NIPPV provides the same support along with breaths delivered at a higher pressure via the ventilator.

What did we want to find out?

We wanted to find out if NIPPV has short-term and long-term benefits without causing harm to premature infants when coming off a ventilator and how it compares with NCPAP.

What did we do?

We searched scientific databases for studies comparing NCPAP versus NIPPV in preterm infants (born before 37 completed weeks of pregnancy) who no longer needed an endotracheal tube. We looked at breathing problems, the need for the endotracheal tube to be reinserted and side effects.

What did we find?

We found 19 trials comparing NCPAP versus NIPPV. When compiling the results of the trials, we found that NIPPV likely reduces the need for reinsertion of the endotracheal tube for very preterm infants (time since first day of the woman's last menstrual cycle to 28 weeks and above). NIPPV may also lead to a reduced number of air leaks from the air spaces of the lungs. There was little to no difference in other outcomes measured in this review.

What are the limitations of the evidence?

In clinical trials, clinicians and investigators were aware of the treatment received by each infant (NIPPV or NCPAP). Therefore, we have moderate confidence in the evidence for breathing problems and need for reinsertion of the endotracheal tube.

How up to date is this evidence?

Evidence is current to January 2023.

Authors' conclusions: 

NIPPV likely reduces the incidence of extubation failure and the need for reintubation within 48 hours to one-week postextubation more effectively than NCPAP in very preterm infants (GA 28 weeks and above). There is a paucity of data for infants less than 28 weeks' gestation. Pulmonary air leaks were also potentially reduced in the NIPPV group. However, it has no effect on other clinically relevant outcomes such as gastrointestinal perforation, NEC, chronic lung disease or mortality. Ventilator-generated NIPPV appears superior to bilevel devices in reducing the incidence of respiratory failure postextubation failure and need for reintubation. Synchronisation used to deliver NIPPV may be important; however, data are insufficient to support strong conclusions.

Future trials should enrol a sufficient number of infants, particularly those less than 28 weeks' GA, to detect differences in death or chronic lung disease and should compare different categories of devices, establish the impact of synchronisation of NIPPV on safety and efficacy of the technique as well as the best combination of settings for NIPPV (rate, peak pressure and positive end-expiratory). Trials should strive to match the mean airway pressure between the intervention groups to allow a better comparison. Neurally adjusted ventilatory assist needs further assessment with properly powered randomised trials.

Read the full abstract...

Nasal continuous positive airway pressure (NCPAP) is a useful method for providing respiratory support after extubation. Nasal intermittent positive pressure ventilation (NIPPV) can augment NCPAP by delivering ventilator breaths via nasal prongs.


Primary objective

To determine the effects of management with NIPPV versus NCPAP on the need for additional ventilatory support in preterm infants whose endotracheal tube was removed after a period of intermittent positive pressure ventilation.

Secondary objectives

To compare rates of abdominal distension, gastrointestinal perforation, necrotising enterocolitis, chronic lung disease, pulmonary air leak, mortality, duration of hospitalisation, rates of apnoea and neurodevelopmental status at 18 to 24 months for NIPPV and NCPAP.

To compare the effect of NIPPV versus NCPAP delivered via ventilators versus bilevel devices, and assess the effects of the synchronisation of ventilation, and the strength of interventions in different economic settings.

Search strategy: 

We used standard, extensive Cochrane search methods. The latest search date was January 2023.

Selection criteria: 

We included randomised and quasi-randomised trials of ventilated preterm infants (less than 37 weeks' gestational age (GA)) ready for extubation to non-invasive respiratory support. Interventions were NIPPV and NCPAP.

Data collection and analysis: 

We used standard Cochrane methods. Our primary outcome was 1. respiratory failure. Our secondary outcomes were 2. endotracheal reintubation, 3. abdominal distension, 4. gastrointestinal perforation, 5. necrotising enterocolitis (NEC), 6. chronic lung disease, 7. pulmonary air leak, 8. mortality, 9. hospitalisation, 10. apnoea and bradycardia, and 11. neurodevelopmental status.

We used GRADE to assess the certainty of evidence.

Main results: 

We included 19 trials (2738 infants). Compared to NCPAP, NIPPV likely reduces the risk of respiratory failure postextubation (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.67 to 0.84; number needed to treat for an additional beneficial outcome (NNTB) 11, 95% CI 8 to 17; 19 trials, 2738 infants; moderate-certainty evidence) and endotracheal reintubation (RR 0.78, 95% CI 0.70 to 0.87; NNTB 12, 95% CI 9 to 25; 17 trials, 2608 infants, moderate-certainty evidence), and may reduce pulmonary air leaks (RR 0.57, 95% CI 0.37 to 0.87; NNTB 50, 95% CI 33 to infinite; 13 trials, 2404 infants; low-certainty evidence). NIPPV likely results in little to no difference in gastrointestinal perforation (RR 0.89, 95% CI 0.58 to 1.38; 8 trials, 1478 infants, low-certainty evidence), NEC (RR 0.86, 95% CI 0.65 to 1.15; 10 trials, 2069 infants; moderate-certainty evidence), chronic lung disease defined as oxygen requirement at 36 weeks (RR 0.93, 95% CI 0.84 to 1.05; 9 trials, 2001 infants; moderate-certainty evidence) and mortality prior to discharge (RR 0.81, 95% CI 0.61 to 1.07; 11 trials, 2258 infants; low-certainty evidence).

When considering subgroup analysis, ventilator-generated NIPPV likely reduces respiratory failure postextubation (RR 0.49, 95% CI 0.40 to 0.62; 1057 infants; I2 = 47%; moderate-certainty evidence), while bilevel devices (RR 0.95, 95% CI 0.77 to 1.17; 716 infants) or a mix of both ventilator-generated and bilevel devices likely results in little to no difference (RR 0.87, 95% CI 0.73 to 1.02; 965 infants).