In 1958, respiratory distress was successfully treated for the first time with mechanical ventilation (MV) on four term neonates in Sweden.1 A few years later, MV significantly decreased neonatal mortality from 80% to around 50% in infants born with gestational age (GA) between 32-36 weeks.2,3 Since then, respiratory care has progressed tremendously with the widespread and successful use of new ventilators, medications, interventions, and different modes of non-invasive respiratory support.4 Importantly, survival of the most extreme preterm population also increased substantially, with MV playing a paramount role.5 Indeed, data from large cohort studies and randomized trials have shown that for infants born with GA between and 25 weeks, 85% to 89% require MV during the first days of age and almost all hospitalization in the neonatal intensive care unit (NICU).6, 7, 8

Although MV offers essential support while the respiratory system matures or recovers from acute failure, it is associated with many short and long-term complications, including long-term neurodevelopmental impairment.9 For that reason, the focus has been on expediting weaning from MV and extubation as fast as possible. However, extubation success rates are lowest in the most immature infants and failure has been associated with significant clinical instability in the form of multiple episodes of hypoxemia and hypercapnia.10 Evidently, both premature extubation and unnecessarily prolonged MV are detrimental. Unfortunately, there is a notable paucity of strong data to guide clinicians on the ideal ways to wean MV or determine extubation readiness11, especially in the micro-preemies (22-24 weeks). In this article, the available literature is reviewed and sensible evidence-based recommendations for efficient MV weaning and extubation are outlined.