Ellen de Kort

130 Chapter 8 judged by the attending physician. If the attending physician judged the patient to be hemodynamically stable enough to receive propofol, the patient could be included in the trial. The studywas registered at ClinicalTrials.gov (NCT02040909; EudraCT number 2013- 005572-17) and approved by the local medical ethics committee (NL47607.078.14, MEC- 2014-0.68). For further details concerning patient stratification, dose-finding approach and the assessment of effective sedation we refer to the initial publication. 14 In summary, dose-finding was performed by using a step-up-step-down approach, starting with a propofol dose of 1.0 mg/kg in five consecutive patients and adjusting the dose with steps of 0.5 mg/kg for the next five patients based on sedative effect and side effects of the previous dose. For this analysis, all patients from the NEOPROP-2 trial who received a propofol starting dose of 1.0, 1.5 and 2.0 mg/kg were included. Patients who received a different starting dose were excluded. Blood pressure assessment Blood pressure was measured invasively if an indwelling arterial catheter was present. Data were collected every minute from 5 minutes before until 30 minutes after the start of propofol administration, every 5 minutes from 30 to 60 minutes and every hour thereafter up to 24 hours. When no arterial catheter was present, blood pressure was measured noninvasively by an appropriately sized cuff every 5 minutes from 5 minutes before until 60 minutes after propofol administration and every hour thereafter until 24 hours. Propofol-induced hypotension was defined as a mean blood pressure (MBP) below postmentrual age (PMA) detected in the first hour after propofol administration. Treatment of hypotension was left to the discretion of the treating physician. Primary outcome measure The primary outcome measure was the course of blood pressure over time in the first hour after start of propofol infusion relative to baseline blood pressure in three different initial propofol starting doses (1.0, 1.5 and 2.0 mg/kg). Blood pressure measured within 5 minutes before start of the propofol infusion was considered as baseline. Blood pressure data were obtained every 5 minutes from 5 minutes before to 60 minutes after the start of propofol infusion. Secondary outcome measures Since the hemodynamic status of the patient could influence the patients’ tolerability for propofol, we evaluated the incidence of hypotension and the change in MBP after start of propofol relative to the baseline MBP in relation to the hemodynamic status of the patient. For this purpose we included all patients in whom sufficient information regarding baseline MBP and MBP in the first hour after propofol was available, and divided these patients into three groups: group 1, hemodynamically stable patients (no