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The aim of this conceptual review is to provide the reader with a broad perspective on progress made in respiratory support of preterm infants over the past five decades. Landmark discoveries are described in their historical context and underlying theories of lung protection are discussed. The review finishes by integrating different approaches and perspectives into a state-of-the-art concept for lung-protective ventilation in this fragile patient population. Improvements in neonatal respiratory support in the 1970s and 1980s have contributed to dramatic improvements of mortality and morbidity rates among neonates with respiratory failure. Continuous positive airway pressure, antenatal corticosteroids and surfactant replacement therapy revolutionized the care of preterm infants. With the recognition that atelectrauma, volutrauma and oxygen toxicity are the main factors contributing to ventilator-induced lung injury, lung-protective strategies, including noninvasive respiratory support, tidal volume targeting during conventional mechanical ventilation and high frequency ventilation were developed in the 1990s. Given the fact that progress made in the last decade has only resulted in minor improvements in mortality and morbidity rates of neonates with respiratory failure, it seems unlikely that further refinements of current technologies will produce giant leaps forward in high-resource countries. It appears that entirely new approaches would be required. In contrast, knowledge and technology transfer of basic respiratory support strategies (e.g. use of oxygen, simple systems to provide continuous positive airway pressure), could have an enormous impact on the prognosis of neonates with respiratory failure in low-resource countries.

Background: Diagnosis of neonatal early-onset sepsis is difficult because clinical signs and laboratory tests are non-specific. Early antibiotic therapy is crucial for treatment success. Objective: To evaluate the effect of procalcitonin (PCT)-guided decision-making on duration of antibiotic therapy in suspected neonatal early-onset sepsis. Methods: This single-center, prospective, randomized intervention study was conducted in a tertiary neonatal and pediatric intensive care unit in the Children’s Hospital of Lucerne, Switzerland, between June 1, 2005 and December 31, 2006. All term and near-term infants (gestational age ≧34 weeks) with suspected early-onset sepsis were randomly assigned either to standard treatment based on conventional laboratory parameters (standard group) or to PCT-guided treatment (PCT group). Minimum duration of antibiotic therapy was 48–72 h in the standard group, whereas in the PCT group antibiotic therapy was discontinued when two consecutive PCT values were below predefined age-adjusted cut-off values. Results: 121 newborns were randomly assigned either to the standard group (n = 61) or the PCT group (n = 60). The two groups were similar for baseline demographics, risk factors for early-onset sepsis, likelihood of infection as assessed by the attending physician and early conventional laboratory findings. There was a significant difference in the proportion of newborns treated with antibiotics ≧72 h between the standard group (82%) and the PCT group (55%) (absolute risk reduction 27%; odds ratio 0.27 (95% CI 0.12–0.62), p = 0.002). On average, PCT-guided decision-making resulted in a shortening of 22.4 h of antibiotic therapy. Clinical outcome was similar and favorable in both groups but sample size was insufficient to exclude rare adverse events. Conclusion:Serial PCT determinations allow to shorten the duration of antibiotic therapy in term and near-term infants with suspected early-onset sepsis. Before this PCT-guided strategy can be recommended, its safety has to be confirmed in a larger cohort of neonates.