Ellen de Kort

111 Propofol for intubation in neonates 7 Dose-finding approach A sample size of five patients per dose per group was used, based on the large inter- individual variability in effects of propofol that was found previously. 17 The first five patients in every group received a starting dose of 1.0 mg/kg propofol. Based on these five patients, the dose was increased or decreased with 0.5 mg/kg in the next five patients up to a maximum starting dose of 3.5 mg/kg because of expected toxicity. If needed for further optimization, a change of 0.25 mg/kg was applicable in the final dose-finding stage. Once the optimal propofol dose had been found, it was confirmed in another five patients. Dose-finding was completed per group when the optimal propofol dose was found, or when the maximum starting dose of 3.5 mg/kg was reached. Primary outcome measures The primary outcome of the study was the optimal single propofol starting dose for intubation in neonates with different GAs and PNAs, defined as the single starting dose that provided effective sedation without significant side effects. Effective sedation was determinedwith two variables that both needed to be adequate: pre-intubation sedation level and quality of intubation. Pre-intubation sedation level was determined with the IRS, and adequate pre-intubation sedation level was defined as IRS 3 or 4. 22 Quality of intubation was determined with the Viby-Mogensen intubation score. 23 Good quality of intubation was defined as a score of ≤2 on each of the five items. Pre-defined side effects included hypotension, myoclonus, chest wall rigidity, persistent respiratory and/or circulatory failure, and bronchospasm. Blood pressure was measured invasively if an indwelling arterial catheter was present. Data were collected everyminute from 5 min before until 30 min after the start of propofol administration, every 5 min from 30 to 60 min and every hour thereafter up to 24 hours. When no arterial catheter was present, blood pressure was measured non-invasively by an appropriately sized cuff every 5 min from 5 min before until 60 min after propofol administration and every hour thereafter until 24 hours. Propofol-induced hypotension was defined as a mean blood pressure (MBP) below postmenstrual age (PMA) detected in the first hour after propofol administration. Treatment of hypotensionwas left to the discretion of the treating physician. For the primary outcome both effective sedation and absence of serious side effects needed to be positive. When either sedation was not effective or there were serious side effects, the primary outcome was not reached. Since both items needed to be positive, in case of one negative item and one missing item, the primary outcome was also not reached.