Review question
How does giving preterm infants low versus moderate-high levels of nasal continuous positive airway pressure (CPAP) impact important health outcomes?
Background
Preterm infants are born earlier than expected. Compared to term infants, preterm infants have immature lungs that are at risk of partial collapse. This collapse makes it difficult for the lungs to bring oxygen into the body and remove carbon dioxide from the body. In response, such infants are commonly treated with nasal CPAP, a therapy that maintains a positive pressure against the airways in an effort to keep the lungs open and to prevent respiratory failure. The pressure is applied through a mask or prongs attached to the nose. Nasal CPAP may be used upon admission to the neonatal intensive care unit as the initial respiratory support and also after a period of mechanical ventilation (use of a breathing machine) and extubation (removal of a breathing tube). Medical providers choose how much pressure to give. The amount of pressure is referred to as the CPAP level, which is measured in units of centimeters of water (cm H2O). Both not enough and too much pressure can be harmful, and it remains uncertain which CPAP pressure levels lead to the best outcomes. We performed a comprehensive search of the medical literature to summarize the impact of using low (≤ 5 cm H2O) versus moderate-high (> 5 cm H2O) initial CPAP pressure levels in preterm infants.
Study characteristics
The search is up-to-date through 6 November 2020. We included 11 studies in the review. Four studies reported health outcomes that we had pre-selected as being relevant to nasal CPAP levels and to the overall health of preterm infants, while the remaining studies reported short-term physiological outcomes such as oxygen levels, heart rate, and blood pressure.
Key results
Of the four studies reporting pre-selected health outcomes, we could only combine data from two studies comparing nasal CPAP levels for initial respiratory support and two studies comparing levels for support following extubation. Based on the data from these studies, we are uncertain as to whether low or moderate-high nasal CPAP levels improve these outcomes. Future studies are needed to answer our review question.
Certainty of evidence
The overall numbers of studies and participants were small, and some of the included studies had flaws potentially limiting the accuracy of their findings. We therefore judged our findings as of very low certainty.
There are insufficient data from randomized trials to guide nasal CPAP level selection in preterm infants, whether provided as initial respiratory support or following extubation from invasive mechanical ventilation. We are uncertain as to whether low or moderate-high nasal CPAP levels improve morbidity and mortality in preterm infants. Well-designed trials evaluating this important aspect of a commonly used neonatal therapy are needed.
Preterm infants are at risk of lung atelectasis due to various anatomical and physiological immaturities, placing them at high risk of respiratory failure and associated harms. Nasal continuous positive airway pressure (CPAP) is a positive pressure applied to the airways via the nares. It helps prevent atelectasis and supports adequate gas exchange in spontaneously breathing infants. Nasal CPAP is used in the care of preterm infants around the world. Despite its common use, the appropriate pressure levels to apply during nasal CPAP use remain uncertain.
To assess the effects of 'low' (≤ 5 cm H2O) versus 'moderate-high' (> 5 cm H2O) initial nasal CPAP pressure levels in preterm infants receiving CPAP either: 1) for initial respiratory support after birth and neonatal resuscitation or 2) following mechanical ventilation and endotracheal extubation.
We ran a comprehensive search on 6 November 2020 in the following databases: CENTRAL via CRS Web and MEDLINE via Ovid. We also searched clinical trials databases and the reference lists of retrieved articles for randomized controlled trials (RCTs) and quasi-randomized trials.
We included RCTs, quasi-RCTs, cluster-RCTs and cross-over RCTs randomizing preterm infants of gestational age < 37 weeks or birth weight < 2500 grams within the first 28 days of life to different nasal CPAP levels.
We used the standard methods of Cochrane Neonatal to collect and analyze data. We used the GRADE approach to assess the certainty of the evidence for the prespecified primary outcomes.
Eleven trials met inclusion criteria of the review. Four trials were parallel-group RCTs reporting our prespecified primary or secondary outcomes. Two trials randomized 316 infants to low versus moderate-high nasal CPAP for initial respiratory support, and two trials randomized 117 infants to low versus moderate-high nasal CPAP following endotracheal extubation. The remaining seven studies were cross-over trials reporting short-term physiological outcomes. The most common potential sources of bias were absent or unclear blinding of personnel and assessors and uncertain selective reporting.
Nasal CPAP for initial respiratory support after birth and neonatal resuscitation
None of the six primary outcomes prespecified for inclusion in the summary of findings was eligible for meta-analysis. No trials reported on moderate-severe neurodevelopmental impairment at 18 to 26 months. The remaining five outcomes were reported in a single trial. On the basis of this trial, we are uncertain whether low or moderate-high nasal CPAP levels improve the outcomes of: death or bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age (PMA) (risk ratio (RR) 1.02, 95% confidence interval (CI) 0.56 to 1.85; 1 trial, 271 participants); mortality by hospital discharge (RR 1.04, 95% CI 0.51 to 2.12; 1 trial, 271 participants); BPD at 28 days of age (RR 1.10, 95% CI 0.56 to 2.17; 1 trial, 271 participants); BPD at 36 weeks' PMA (RR 0.80, 95% CI 0.25 to 2.57; 1 trial, 271 participants), and treatment failure or need for mechanical ventilation (RR 1.00, 95% CI 0.63 to 1.57; 1 trial, 271 participants). We assessed the certainty of the evidence as very low for all five outcomes due to risk of bias, a lack of consistency across multiple studies, and imprecise effect estimates.
Nasal CPAP following mechanical ventilation and endotracheal extubation
One of the six primary outcomes prespecified for inclusion in the summary of findings was eligible for meta-analysis. On the basis of these data, we are uncertain whether low or moderate-high nasal CPAP levels improve the outcome of treatment failure or need for mechanical ventilation (RR 1.52, 95% CI 0.92 to 2.50; 2 trials, 117 participants; I2 = 17%; risk difference 0.15, 95% CI −0.02 to 0.32; number needed to treat for an additional beneficial outcome 7, 95% CI −50 to 3). We assessed the certainty of the evidence as very low due to risk of bias, inconsistency across the studies, and imprecise effect estimates. No trials reported on moderate-severe neurodevelopmental impairment at 18 to 26 months or BPD at 28 days of age. The remaining three outcomes were reported in a single trial. On the basis of this trial, we are uncertain whether low or moderate-high nasal CPAP levels improve the outcomes of: death or BPD at 36 weeks' PMA (RR 0.87, 95% CI 0.51 to 1.49; 1 trial, 93 participants); mortality by hospital discharge (RR 2.94, 95% CI 0.12 to 70.30; 1 trial, 93 participants), and BPD at 36 weeks' PMA (RR 0.87, 95% CI 0.51 to 1.49; 1 trial, 93 participants). We assessed the certainty of the evidence as very low for all three outcomes due to risk of bias, a lack of consistency across multiple studies, and imprecise effect estimates.