Ellen de Kort

175 Summary 10 PREMEDICATION DURING INSURE AND LISA Respiratory Distress Syndrome (RDS) in preterm infants is often treated with surfactant. Historically, surfactant was administered during a period of mechanical ventilation. To prevent ventilator-induced lung injury, lesser invasive ways to administer surfactant were developed: the INSURE (INtubation-SURfactant-Extubation) procedure and the LISA (Less Invasive Surfactant Application) procedure. During the INSURE procedure, an endotracheal tube is placed in the trachea and surfactant is administered, followed by immediate extubation. To facilitate immediate extubation, the premedication that is used to provide sedation and comfort during placement of the endotracheal tube, should have a very short period of action, to allow for quick restoration of the respiratory drive. To determine which drug or combination of drugs would be most appropriate as premedication prior to the INSURE procedure, we performed a systematic review of the literature ( chapter 2 ). Our literature search only revealed two publications explicitly evaluating the effect of a certain premedication for the INSURE procedure: remifentanil (2 μg/kg) and propofol (1 mg/kg). Both strategies provided adequate sedation, but the study on propofol was prematurely ended because of serious side effects. In both studies, the time to start with continuous positive airway pressure (CPAP) and the time to extubation were rather long but reasons for this were not provided. The period of action of both remifentanil and propofol could have been too long to enable immediate extubation. An additional search and inclusion of 10 publications describing the use of premedication during INSURE, did not provide enough information about the period of action of different premedication strategies that were used. The results of this review concluded that, although propofol and remifentanil should in theory both be appropriate candidates, further research into the optimal dose, side effects and period of action of both drugs is needed. Based on its pharmacological profile and the results from our systematic review, we performed a pilot study aiming to evaluate the effect and side effects of remifentanil as premedication prior to INSURE, described in chapter 3 . Remifentanil was administered as a bolus followed by a saline flush with a total duration of 30 seconds. We started with a remifentanil dose of 1 µg/kg, to be repeated twice in the same dose in case of insufficient sedation. Because this strategy only provided sufficient sedation in one out of five patients, we changed the dosing regimen into a starting dose of 2 µg/kg, with additional doses increasing with 1 µg/kg relative to the previous dose up to a maximum dose of 5 µg/kg in case of insufficient sedation. This regimen led to sufficient sedation