One of the trials we have been waiting for has just been published Dargaville PA, et al. Effect of Minimally Invasive Surfactant Therapy vs Sham Treatment on Death or Bronchopulmonary Dysplasia in Preterm Infants With Respiratory Distress Syndrome: The OPTIMIST-A Randomized Clinical Trial. JAMA. 2021;326(24):2478-87. As you can see above, there was “no significant difference” in the primary outcome of death or BPD, as defined by needing more than 30% O2, or being on respiratory support, or having <30% oxygen and failing a room air challenge, all at 36 weeks. I have ranted often enough about this outcome that I won’t repeat it here. I will say that I think OPTIMIST is the second best trial name ever in neonatology (after ELVIS), but maybe it was too OPTIMISTIC to think that there would be a large reduction in BPD in the most immature infants who were stable enough to be eligible for this study. To be eligible the baby had to be breathing sponatneously on CPAP in the NICU, so many of the sickest babies, would already be intubated, and infants thought to be in need of immediate intubation were also excluded. Those are quite appropriate exclusions, but it means that the remaining babies were relatively lower risk infants.
I’m trying out a new format with a sort of home-made visual summary of the article that you can see above, but it’s quite a lot of extra work, so I don’t know if I’ll continue. Anyway, my bottom line is that MIST looks positive for the 27 and 28 week infants, but the unexpected increase in mortality at 25-26 weeks gives me pause. Apparently the causes of mortality were distributed among all the usual causes, which is a bit strange as all the usual adverse outcomes were slightly less common with MIST, late onset sepsis, NEC, spontaneous perforation and IVH.
As usual, I hate to say it, but I think we need another study. A trial with even earlier surfactant, perhaps prophylactic MIST or at 25 % oxygen, and concentrating on the more immature infants, perhaps combined with a higher dose of caffeine.
I think if such a trial could show the pulmonary benefits, in particular the reduction in home oxygen therapy, without a mortality effect, then MIST/LISA could become routine for the very immature, 25 to 26 week infant. Until then, I think that an overall benefit in those babies is not proven.