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.
Neonatal Research 
Hi Keith, Thanks for your blog. To answer your comment about “weird thing”, we actually submitted the manuscript to 2 different journals in 2013/2014 and it was rejected on both occasions – most likely due to small sample size. I was a bit disheartened, and then also became overwhelmed with work commitments, and co-authors had moved away. I came back to it in 2018 whilst on sabbatical with the encouragement of peers, and we finally found a home for it on our fourth attempt – despite the manuscript being essentially unchanged from initial submission 5 years ago! Pari did not influence publication. Regards, Jane
Thanks for the details Jane, it is comforting to know there was no influence of Pari, and that some extremely effective people like you can still take a few years to publish their data! I still have a few things in my drawers that should have been published, and probably never will be, unfortunately.
Hi Dr. Barrington:
I am a veterinary anesthesiologist working at the college of vet med at Cornell University. We have recently received some doses of an exogenous surfactant that we want to use in our premature foals that are many times born with respiratory distress syndrome. We have surfactnat from Ony Biotech and we are using their nebulizers. However, given the size of the neonatal foal compared with the neonatal human, we are struggling with duration of nebulization and are wondering if we should switch altogether to a rapid intubation and direct tracheal instillation instead. Do you have any suggestions as to what path to take?. My email is below but I am adding it here also: jda246@cornell.edu
Thank you very much in advance.
Unusual question for me! I don’t know how effective nebulization will be in the foal. If the little guy is around 50kg, and you use the same dose of Infasurf as used in the trial that will be about 10,000 mg of phospholipid or about 300 mL of the stuff. Might take a long time to nebulize. Also, that is double the dose usually given when intubated so it will cost double.
Also in the trial, quite a lot of babies needed intubating anyway to give them surfactant, so from my vast experience of mammalian newborn intensive care, I think that it would probably be better to either intubate them and give a bolus dose. You might also try a LISA like approach, if it is technically possible in a foal, that is to visualize the glottis and pass a thin catheter through the cords and then inject the surfactant through the catheter and immediately withdraw it.
Good luck!
I agree with Dr Barrington. Given the volume of surfactant required, the most effective delivery route for exogenous surfactant would be using the LISA method with the foal breathing spontaneously. However, surfactant is a very expensive treatment if you do not also combine it with CPAP – preferably using a dynamic CPAP to promote recruitment of the atelectatic lung. Best results are obtained when you recruit the lung before as well as after surfactant. Bubble CPAP offers advantages for the derecruited lung due to the stochastic recruitment of the lung promoted by the noisy pressure waveform – which also enhances CO2 clearance and airway patency. Australian veterinary colleagues used Bubble CPAP successfully in newborn foals with RDS (without need for then using expensive surfactant). Feel free to contact me at jane.pillow@uwa.edu.au for more details.
Thanks. Great to have a comment from a real expert in nebulized surfactant!