Ellen de Kort

179 Summary 10 could not be established. In both groups, a propofol dose of 2.0 mg/kg was found to achieve effective sedation, but caused hypotension in more than half of the patients. Further in-depth analysis of the three most used propofol starting doses showed that starting doses of 1.0 and 1.5 mg/kg almost never led to effective sedation. Only a starting dose of 2.0 mg/kg caused effective sedation in the majority of patients. In all three dosing groups, however, more than half of all patients developed hypotension. In the total study population, mean blood pressure after propofol administration decreased with a median of 34% compared to the mean blood pressure at baseline. The lowest mean blood pressure occurred at a median of 21 minutes after the start of propofol administration. Logistic regression analysis showed that gestational age and postnatal age, as well as other patient characteristics, did not influence the sedative effect of propofol and the occurrence of hypotension. Based on these results it can be concluded that effective sedation without the occurrence of side effects is difficult to achieve with a single propofol bolus. Effects as well as side effects of propofol in the neonatal population are variable and unpredictable. Therefore, propofol in the neonatal population should only be used after careful consideration and should be titrated based on sedative effect with strict monitoring of blood pressure. A post-hoc analysis of the propofol dose-finding trial, aiming to provide guidelines for the use of propofol in clinical practice, studied the effects of different propofol starting doses on blood pressure ( chapter 8 ). In both the 1.0 mg/kg, 1.5 mg/kg and 2.0 mg/kg starting doses blood pressure declined after the start of propofol compared to baseline blood pressure before propofol. This decline was dose-dependent, being the largest in the 2.0 mg/kg dosing group. In all three dosing groups, blood pressure was not restored one hour after the start of propofol. The decline in blood pressure was mainly dependent on the starting dose of propofol that was used and not on the cumulative propofol dose that was eventually administered to provide sufficient sedation and accomplish successful intubation. The incidence of hypotension, the treatment of hypotension with volume resuscitation and the maximum decrease in blood pressure as percentage from baseline were all not statistically different between the 1.0 mg/kg, 1.5 mg/kg and 2.0 mg/kg dosing groups. The maximum decrease in blood pressure, however, was significantly earlier in the 1.0 mg/kg dosing group compared to the 2.0 mg/kg dosing group. In conclusion, propofol causes a profound and prolonged decrease in blood pressure that is mainly dependent on the propofol starting dose that is used. These results again stress the need for careful consideration of propofol as premedication in the newborn population. When propofol is used, starting with a low dose and titrating until sufficient sedation is reached, seems to cause the least decline in blood pressure and therefore, seems the safest or least unsafe strategy.