ViewpointLess invasive surfactant administration: a word of caution
Section snippets
Background
Surfactant is a cornerstone of neonatal critical care and has drastically improved the care of preterm babies with respiratory distress syndrome due to primary surfactant deficiency.1, 2 Surfactant is usually administered via an endotracheal tube followed by mechanical ventilation. Duration of mechanical ventilation has been shortened as much as possible, given its deleterious effect on the developing lung. Thus, the intubation, surfactant, and extubation (INSURE) technique has been diffused on
The importance of pathobiological and physiopathological background
The US Food and Drug Administration recommends that the development of a medical procedure or device should follow a pathway similar to that of pharmacological research. Therefore, although the process can vary among different countries, procedures and devices should be preliminarily tested in laboratory settings, animal models, or both, then assessed in clinical trials of increasing complexity, provided that there is a solid pathobiological background that leads the researcher to hypothesise a
Benefits of less invasive techniques
It is difficult to find solid pathobiological reasons justifying clinical benefits linked to these new surfactant administration techniques. Essentially, it is important to understand how the reduction in tube diameter may have clinical advantages, if it is uncoupled with other changes in the procedure itself, such as different sedation or ventilation policies. The following physiopathological hypotheses associated with LISA have been formulated and deserve to be discussed: improved CPAP
Detrimental effects of less invasive techniques
A 2017 European survey reported short-term adverse effects of LISA, which seem similar to those of INSURE, although whether these effects are worse with one technique than the other is unclear.75 Given the shared need for laryngoscopy and the similarities of the two techniques, most of these side-effects should be transient and evenly distributed between the two techniques.
However, some points should be highlighted. We have previously shown that the use of thin feeding catheters leads to
Critical appraisal of randomised controlled trials
Two meta-analyses have shown the benefits of LISA techniques.84, 85 Meanwhile, the number of published trials has risen to eight;6, 86, 87, 88, 89, 90, 91, 92 only two of them have a multicentre design.6, 86 Five of them have been done in low-income or middle-income countries,88, 89, 90, 91, 92 and the three larger studies in well established neonatal units.6, 86, 87 These trials have methodological biases, like any other, and only some of them are well described in the original manuscripts and
Future research and development
A practical guide about LISA was published during the revision of this manuscript, by colleagues with expertise in LISA techniques.94 The questions about the transmission of CPAP, the need for sedation, and the unlikely risk of INSURE-related lung injury remain unanswered. Conversely, the described flaws in the physiopathological background of LISA trials and their ambiguous message are echoed. In particular, reliable comparisons of LISA versus well performed INSURE are lacking and, in fact, a
Acknowledgments
We are grateful to Lucilla Pezza for her kind help to create the artwork.
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