Ellen de Kort

157 General discussion 9 intubation, because of the slow onset of action and slow clearance. 49 The superior effect of propofol compared to the combination of morphine and suxamethonium used by Ghanta et al., therefore, could possibly be influenced by insufficient analgesia and/or sedation by the time intubation was performed. Results could have been different if short-acting opioids had been used. Several studies provided conflicting results on the sedative effect of different propofol doses. 38,56-58 In all studies equal propofol doses in the entire population of neonates were used, despite the fact that gestational age and postnatal age have been proven to be important determinants of propofol pharmacokinetics. 59 Smits et al. were the first to show that different doses of propofol were needed to provide adequate sedation in groups of neonates with different gestational and postnatal ages. 60 In our NEOPROP-2 trial, a multicenter dose-finding study, we aimed to find the single propofol starting dose that provides effective sedation without side effects in eight groups of patients with different gestational and postnatal ages. Unfortunately, wewere not able to establish this propofol dose in any of the eight age groups. We did find that, regardless of gestational age or postnatal age, single propofol starting doses of 1.0 and 1.5 mg/kg almost never led to effective sedation. Only a single dose of 2.0mg/kg led to effective sedation in the majority of patients. Logistic regression analysis showed that the sedative effect of propofol was not influenced by gestational or postnatal age. 61 From these findings it can be concluded that the sedative effect of propofol is dose-dependent in general, but unpredictable in the individual patient. Ameta-analysis of the available studies might provide final conclusions about the appropriate propofol doses. The existing evidence on the effect of propofol on blood pressure is also conflicting. While in some studies hypotension did not appear 38,62 or did only appear in a small proportion of patients, 56,63 other authors reported a 38 to 65% incidence of hypotension. 57,58,60 The high incidence of hypotension was confirmed in our NEOPROP-2 trial. We found an overall incidence of 59% and incidences of 63%, 52% and 62% in 1.0 mg/kg, 1.5 mg/ kg and 2.0 mg/kg starting doses. 61 In a post-hoc analysis of the NEOPROP-2 data we showed that there was a significant decline in blood pressure in all three dosing groups, which was not restored after one hour. This decline in blood pressure was dependent on the starting dose and not on the cumulative propofol dose. 64 In a multiple regression analysis with gestational age, postnatal age, growth restriction (defined as a birth weight below 10 th percentile) and male gender as patient variables, we were not able to define factors that could influence the occurrence of propofol-induced hypotension. 61 Other possible influencing factors such as underlying illness and disease severity need further investigation.