- Bartlett, R. H., Roloff, D. W., Cornell, R. G., Andrews, A. F., Dillon, P. W., & Zwischenberger, J. B. (1985). Extracorporeal-Circulation in Neonatal Respiratory-Failure – a Prospective Randomized Study. Pediatrics, 76(4), 479-487. http://pediatrics.aappublications.org/content/76/4/479.full.pdf+html
This study is interesting because Dr Bartlett, who was THE pioneer of neonatal ECMO, was criticized for not doing a trial; he then did a trial according to some pre-existing suggestions to minimize deaths in potentially life-saving trials. He was then criticized for doing the trial! This randomized trial had an adaptive randomization scheme which increased the likelihood of being put in the treatment arm where you were more likely to survive. So the trial ended with 1 control patient (who died) and 11 ECMO patients who all survived.
- U. K. Collaborative ECMO Trial Group,. (1996). UK collaborative randomised trial of neonatal extracorporeal membrane oxygenation. Lancet, 348(9020), 75-82. http://www.sciencedirect.com/science/article/pii/S0140673696041001
10 years later we Brits finally got around to doing a trial in a country with a historic resistance to invasive treatments. 185 infants from around the country were randomized to either stay were they were and continue receiving conventional treatment, or be transported to an ECMO center for ECMO. The main entry criterion was an OI greater than 40, but 40% had an OI greater than 60. Even though this pragmatic design tilts the chances against ECMO and toward control, mortality was much higher among controls, indeed the study was stopped early. Several long term follow up publications have shown that the ECMO treated kids are doing as well or better than the controls, most survivors have cognitive scores in the normal range, and there are higher respiratory morbidity and increased risk of behavioral problems among controls. Progressive sensorineural hearing loss occurs in both groups.
- The Neonatal Inhaled Nitric Oxide Study Group. (1997). Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure. New Engl J Med, 336(9), 597-604. http://www.nejm.org/doi/full/10.1056/NEJM199702273360901
The largest and best of the full term inhaled NO trials. Significant reduction in the combined outcome of ‘death or ECMO’ among 235 term and near-term infants who were randomized to iNO or placebo if they reached an OI of at least 25.
- (NINOS), The Neonatal inhaled Nitric Oxide Study Group (1997). Inhaled nitric oxide and respiratory failure in infants with congenital diaphragmatic hernia. Pediatr, 99, 838-845. http://pediatrics.aappublications.org/content/99/6/838.abstract
A sub-study of the NINOS group which enrolled infants with diaphragmatic Hernia until the main study was finished. 53 infants were enrolled. There was no benefit of inhaled NO compared to control for the outcomes of survival or needing ECMO.
And then of course there are the Cochrane systematic reviews of nitric oxide in the term and near-term infant, confirming the efficacy in this group of patients with hypoxic respiratory failure. (Both are in revision and new links will be posted when available).
The systematic review of inhaled NO use in the preterm, showing that there was no subgroup of trials that clearly show a benefit in the preterm infant.