Ellen de Kort

112 Chapter 7 Secondary outcome measures Secondary outcomes were the optimal propofol starting dose in the entire study population (regardless of age group), the need for additional doses of propofol and side effects in the entire study population and sedative effect and side effects in the most frequently used propofol starting doses. Finally, a logistic regression analysis was performed to find potential variables predicting the sedative effect and side effects after propofol. Statistical analysis The predefined sample size depended on which propofol dose was found to be adequate in five consecutive patients per group. Data were analyzed using SPSS (IBM SPSS Statistics for Windows, version 22.0. Armonk, NY, USA), and R 3.5 (R Core Team, Vienna, Austria). Patients were analyzed according to the intention-to-treat principle. Baseline characteristics were described by percentages for qualitative variables and median (interquartile range [IQR]) for quantitative variables. Comparison between dosing groups was performed with the Mann-Whitney U test for continuous variables and the Pearson’s Chi square test or the Fisher’s exact test, as appropriate, for categorical variables. Logistic regression analysis was performed to identify factors influencing the sedative effect and side effects of propofol with primary outcome, effective sedation, and hypotension as outcome variables. We analyzed the effects of gestational age (weeks), birth weight <10 th percentile, male gender, postnatal age (hours), and propofol starting dose (mg/kg) on primary outcome and effective sedation. Total amount of propofol (mg/kg) was added as a confounder in the logistic regression analysis with hypotension as outcome variable. We used the Firth’s method to reduce the bias in logistic regression that arises as a consequence of the relatively small sample size. 24,25 RESULTS Study population The study population consisted of 91 patients (see Table 1). Three patients were included despite their PNA exceeding 28 days (two patients in group 2 [39 and 32 days] and one patient in group 4 [29 days]). Study termination An interim analysis after inclusion of 91 patients demonstrated a low inclusion rate in several groups and a 59% incidence of hypotension. In two age groups a propofol dose that provided effective sedation was found but caused hypotension in the majority of