ECMO or no ECMO: Do no harm.

Extracorporeal membrane oxygenation (ECMO) has been used in the management of neonates with life-threatening cardiorespiratory diseases since 19821. Several studies have demonstrated that ECMO promotes normal survival in neonates with respiratory failure2-4. After decades of discussion, ECMO is now well accepted as a standard of treatment for neonatal respiratory failure refractory to conventional techniques of pulmonary support. The randomized controlled study done by the UK collaborative ECMO trial group4 has definitely proven the efficacy of ECMO at a time when nowhere in North America this study could have been undertaken. Over the past several years, other therapies such as surfactant replacement, high-frequency oscillatory ventilation (HFOV), and inhaled nitric oxide (iNO) have been introduced and used increasingly in the management of these critically ill infants5. Among premature infants with respiratory distress syndrome, surfactant-replacement therapy was shown to reduce mortality6. Following an analysis of patients reported to the Extracorporeal Life Support Organization (ELSO) registry5, it was found that the use of surfactant has been now extended to term or near-term neonates with meconium aspiration syndrome, pneumonia and congenital diaphragmatic hernia. In 1988, no patients had received surfactant prior to ECMO institution. However, in 1997, surfactant administration was reported in 36% of patients. This followed the report by Findlay et al7 showing that surfactant in term infants with meconium aspiration syndrome decreased air leak, requirement for ECMO, days on oxygen, days on the ventilator and days in hospital. Lotze et al8 also examined the effect of surfactant in babies with persistent pulmonary hypertension of the newborn (PPHN), meconium aspiration syndrome and sepsis, and found a significant reduction in the need for ECMO. In a prospective randomized trial, HFOV was successful in 48% of neonatal ECMO candidates whereas continued intermittent positive pressure ventilation (IPPV) only in 26%9. Only about 50% of neonates meeting criteria for ECMO required ECMO after a trial of HFOV in another prospective cohort studies10,11. These results have been largely supported by clinical experience. Although it is currently not possible to predict which infants will respond to HFOV, it appears appropriate to most clinicians to try HFOV in infants with PPHN who fail conventional ventilation. NO is produced in vascular endothelial cells and plays an important role in the increase in pulmonary blood flow after birth12-18. Exogenously administered, NO causes selective pulmonary vasodilation in newborn lambs (12). In human neonates, iNO was shown to improve oxygenation in 50% of cases19,20 and furthermore, decreases the need for ECMO19-21. However, iNO is ineffective in congenital diaphragmatic hernia22. Of interest, when iNO is combined to HFOV, a better response is obtained than when each of the therapy is used alone23. Considering that these therapies decrease the need for ECMO9-11,19,24-26, they will necessarily impact on the type of patients treated with ECMO and may potentially change the general outcome of patients treated with ECMO. In a study done for ELSO, Roy et al5 showed that the proportion of neonates with congenital diaphragmatic hernia increased from 18% to 26% between the late 80’s and the late 90’s. This may signify for a particular ECMO center that a greater proportion of the ECMO patients will be more challenging. In this same study, the overall mortality increased from 18% to 22%, but diagnoses-specific mortality rate was unchanged. However, it remains of a particular concern that such therapies may potentially delay the institution of ECMO, the lungs of these neonates may undergo additional barotrauma and neonates may even be excluded from subsequent ECMO if the ventilation period is prolonged. In fact, in a prospective study of 34 neonates of at least 34-week gestation that met ECMO criteria i.e. oxygenation index (OI) greater than 40, 2 patients were denied ECMO because they had undergone already