After the PAS meeting I blogged about a presented abstract of nebulized lucinactant, which showed a possible reduction in needing intubation among babies on CPAP who received the surfactant, compared to controls.
A new publication from Perth (Minocchieri S, et al. Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial. Archives of disease in childhood Fetal and neonatal edition. 2018) reports a similar study, but using poractant and a different type of nebulizer. The authors randomized 64 babies, between 29 and 33 weeks gestation with HMD, to CPAP or to CPAP with the nebulizer placed between the bubble CPAP circuit and the face mask. Infants were eligible if less than 4 hours old, on CPAP of 5 to 8 cmH2O and needed some oxygen, but less than 30%. Treated infants received 200 mg/kg via nebulization, and 100mg/kg if they needed re-treating.
Despite the difficulties, this was done as a masked trial with the surfactant team behind a screen during the administration of surfactant (or equivalent period for the controls).
Failure of assigned treatment was determined by an increase in FiO2 to more than 35% for over 30 minutes, or over 40%, or a respiratory acidosis (CO2>65 and pH<7.2) or multiple apneas or if the physician got fed up (intubation “deemed necessary” but without the other criteria).
The need for intubation within 72 hours was reduced from 22/32 controls to 11/32 surfactant nebulizer babies. This was a short term pilot study, but seems again to show the potential benefit of this intervention, at least for the larger babies; among the babies in this trial, a subgroup analysis suggested benefit only in the more mature babies, but the study was underpowered for such analyses.
The only weird thing about the study is that is was performed between 2010 and 2012, it isn’t clear why it took 6 years to publish it after the end of the trial. I don’t know if that could be related to the fact that the first author has a patent with PARI pharma for the nebulizer.
Many of the intubations, especially of the smaller babies, were because of physician preference. With many of us now being more comfortable having babies on CPAP despite moderate respiratory distress (especially the 29 to 30 week gestation babies) physician preference might well be different if a similar study was redone.
None of the babies developed BPD or IVH or NEC, which makes one wonder, what is the benefit to the infants of avoiding intubation? If our outcomes for such babies are already excellent, is reducing the number or duration of intubation a significant advantage? I would say that in the short term there are advantages, to the baby and the family; intubation is associated with serious physiologic disturbance (and major pain unless you use good analgesia), multiple attempts are often required with increased risks, not likely to show up in a small pilot trial. Seeing a baby intubated rather than on CPAP is probably more stressful for the parents.
Also if we can prove efficacy in the larger early preterm babies, testing the intervention in the more immature babies, and intervening very early, would really be worth doing and may produce further benefits.