This post “under pressure” isn’t about the classic collaboration between David Bowie and Queen at Live Aid, rather it is about how to wean CPAP. Should we trial preterm babies off for a period every day, or either progressively reduce the distending pressure or just stop it? If we do any of those things, the details of how to do it might make a difference. Is weaning to high-flow cannulae better than just stopping the CPAP and using low flow, if O2 is still required?

A few recent studies are relevant to these questions. The best outcome for such studies would probably be something like clinical pulmonary disease at 2 years of age, and, as an important secondary, some metric of respiratory support use, such as in hospital costs, or total duration of CPAP use. It is unlikely we will ever have adequately powered studies to show that stopping CPAP by weaning pressures, compared to progressively weaning off-CPAP time (as an example of a study that could be done) will change the number of infants who are re-admitted for respiratory decompensation during the first year of life.

I guess you could do a study with enough power to show whether one way of weaning, compared to another, led to fewer infants being on oxygen at 36 weeks (i.e. classical “BPD”) but I am increasingly sceptical about this as a measure of pulmonary injury. Acutely reducing lung inflammation with steroids (for example) might decrease the numbers of babies with “BPD” without actually improving the long-term pulmonary health of any of them. Similarly maintaining good lung volume might do a similar thing, whereas overdistension might do the opposite, but the consequences for long term pulmonary health might still be unclear. Despite the limitations of this definition, however, it is still usually collected as the primary variable reflecting lung injury in the preterm.

The Cochrane review of CPAP weaning methods hasn’t been updated since 2011, so the studies below are not included in that review.

Here is a selection of recent publications, starting with the most recent:

Jensen CF, et al. Sudden vs Pressure Wean From Nasal Continuous Positive Airway Pressure in Infants Born Before 32 Weeks of Gestation: A Randomized Clinical Trial. JAMA Pediatr. 2018;172(9):824-31. This Danish group enrolled 372 babies, less than 32 weeks gestation, at least 29 weeks Post-Menstrual Age (PMA), on CPAP for at least 24 hours, <8 cmH2O and <30% O2. They were randomized to either suddenly stopping the CPAP, or decreasing by 1 cmH2O every 24 hours until they reached 4, then stopping. The primary outcome was weight gain, which wasn’t different, and all of the secondary outcomes, including those related to lung function and respiratory support duration, were similar between groups. According to the way the manuscript is written a baby on CPAP of 4 would have been eligible for the study, in which case the intervention in the 2 groups would have been identical. A baby on a CPAP of 5 would have frequently only had 1 day difference in duration of CPAP support, unless the reduction to 4 was not tolerated. The median CPAP at randomization was actually 6 in each group. Overall there were no differences in any outcome when the whole group was analyzed. In a subgroup analysis of babies <28 weeks gestation (n=58), more babies were weaned at the first attempt with the gradual pressure wean than the sudden wean, but they had just as long on oxygen, just as many on oxygen at 36 weeks etc.

Yang CY, et al. A randomized pilot study comparing the role of PEEP, O2 flow, and high-flow air for weaning of ventilatory support in very low birth weight infants. Pediatr Neonatol. 2018;59(2):198-204. In a study from Taiwan, babies < 1500g and <30 wk GA on CPAP 5 to 7 cmH2O, were randomized when they weighed at least 750g and on no more than 25% O2. There were about 180 babies in 3 groups: 5 days of CPAP 4-6 cmH2O; progressively increasing time on 0.2 L/Min O2; progressively increasing time on 1.5 L/min of air. They showed a shorter duration of CPAP in the 2nd group, but no other relevant differences, and the 2nd group may well have been unnecessarily hyperoxic, and had more RoP and BPD than the other groups.

Eze N, et al. Comparison of sprinting vs non-sprinting to wean nasal continuous positive airway pressure off in very preterm infants. J Perinatol. 2017;38:164. In Los Angeles/ Orange county, 80 babies of 23 to 30 weeks GA, who had reached at least 26 weeks PMA, and were on CPAP for at least 24 hours, at 5 to 6 cmH2O were randomized to progressively increasing times off CPAP versus reducing CPAP to 5 cmH2O for at least 96h, then stopping the CPAP. In either group they could have nasal cannulae up to 2 L/min if needed and up to 30% O2. The primary outcome was succesful weaning on 1st attempt, and there were no differences in any outcome between groups.

Amatya S, et al. Sudden versus gradual pressure wean from Nasal CPAP in preterm infants: a randomized controlled trial. J Perinatol. 2017;37(6):662-7.   A group from New York studied 70 babies on a CPAP 5 and 21% O2, who either had CPAP reduced by 1 cm every 8h down to 3 cmH2O, or just stopped. The primary outcome was the success of the first attempt to wean, which was more frequent in the gradual pressure wean group, but no other outcomes were different including total duration of oxygen therapy, and duration of CPAP, or weight gain.

Nair V, et al. Effect of Nasal Continuous Positive Airway Pressure (NCPAP) Cycling and Continuous NCPAP on Successful Weaning: A Randomized Controlled Trial. Indian J Pediatr. 2015;82(9):787-93. A study from Calgary studied babies of 25 to 28 weeks GA who had been extubated and were on CPAP for at least 72 hours and were down to 4 cmH2O. They were either left on for another 72 hours then taken off, or they were placed on nasal cannulae at 1 L/min for progressively increasing periods. The primary outcome was succesful weaning at the first attempt, and it did not differ between groups. None of the secondary outcomes differed either.

Tang J, et al. Randomised controlled trial of weaning strategies for preterm infants on nasal continuous positive airway pressure. BMC pediatrics. 2015;15(1):147. In Sydney, 60 babies who were on CPAP of 5 or less, were studied in a 2X2 factorial design, HFNC vs no HFNC after wean, and sudden wean versus gradually increasing time off CPAP (starting at 6h on and 1 h off). Primary outcomes were 1) BPD (O2 at 36 wk); 2) days pf respiratory support; 3) days of hospital stay; and 4) days to achieve full suck feeds. None of the primary outcomes differed between comparisons, (high flow vs no high flow, or abrupt wean compared to progressively prolonging time off. But the abrupt wean group  had fewer days CPAP (10.5 vs 16.5 d; p = 0.02), lower PMA when CPAP was stopped (33.1 vs 34.6 wks; p = 0.05), and fewer days pressure support (21.5 vs 27.5 d; p = 0.04).

Rastogi S, et al. Gradual Versus Sudden Weaning From Nasal CPAP in Preterm Infants: A Pilot Randomized Controlled Trial. Respiratory Care. 2013;58(3):511-6. This study, from the same group in New York, studied a progressive increase in time off compared to sudden stopping of the CPAP in 56 babies of 32 weeks GA or less who had been on CPAP at least 48 hours. The primary outcome was success of the first weaning attempt, which was not different between groups, none of the secondary outcomes was significant either.

Todd DA, et al. Methods of weaning preterm babies <30 weeks gestation off CPAP: a multicentre randomised controlled trial. Archives of disease in childhood Fetal and neonatal edition. 2012;97(4):F236-40. This is the CICADA trial, in which 177 babies on 4 to 6 CPAP and <25% O2 were randomized to one of 3 methods, sudden wean, progressively increasing time off CPAP, and progressively increasing time off combined with moderate flow nasal cannulae (0.5 litres/min, variable FiO2). Babies in the sudden wean group had shorter time on CPAP, came off CPAP at an earlier post-menstrual age, were less likely to be on oxygen at 36 weeks and went home earlier.

What to make of all that? Well it seems that there is no advantage of weaning by progressively increasing time off in any of the studies, and it may well lead to more failures and a longer duration of O2 therapy. It may be that a progressive weaning of pressure to 3 or 4 cmH2O leads to fewer failures in the short term, but there doesn’t seem to be a big advantage, compared to just stopping from 5 cmH2O when the baby satisfies readiness criteria, which were different among studies, but generally required a low stable FiO2 and little respiratory distress, without significant tachypnea.