Ellen de Kort

33 Sedation for the INSURE procedure 2 immediate extubation. To our opinion it therefore feels somewhat preliminary to state that remifentanil is an appropriate sedative to use as premedication for neonatal intubation during the INSURE procedure. Reduced clearance of remifentanil in the first postnatal days could probably explain the prolonged effect, and it would seem desirable to evaluate lower remifentanil doses that have not yet been studied. More research with remifentanil during the INSURE procedure in a larger group of preterm infants of variable gestational ages is needed. Propofol is a short acting anesthetic that is rapid in onset and short in duration and can preserve spontaneous respirations. 40 It is a highly lipophilic compound and exhibits rapid distribution from blood into subcutaneous fat and the central nervous system with subsequent redistribution. Propofol clearance mainly depends on hepatic blood flow with subsequent metabolism. Although multiple hepatic and extrahepatic human cytochrome p450 isoforms are involved in propofol metabolism, glucuronidation is the major metabolic pathway. 41 A study of Ghanta et al. found that, with the use of propofol 2.5 mg/kg, successful intubation was reached twice as fast as with the combination of morphine, atropine and suxamethonium, fewer attempts were needed, and patients regained spontaneous movements twice as fast. 12 Nevertheless, several studies have shown reduced propofol clearance notably in preterm neonates and neonates in the first 10 days of life, leading to accumulation of the drug during continuous infusion and bolus administration. Preterm neonates and neonates in the first 10 days of life are even more prone to display reduced clearance. After correcting for postmenstrual age and postnatal age, there is still extensive unexplained interindividual variability in propofol clearance in neonates, making prediction in neonates more difficult. 40-43 Welzing et al. evaluated the effect of propofol in a dose of 1 mg/kg in 13 patients undergoing INSURE. Propofol seemed to be very suitable and provided excellent or good intubation conditions in most patients and a very short period of respiratory depression. 17 We feel, however, that the 25 minutes’ time to extubation is too long. Also, one patient needed reintubation because of insufficient breathing. Again, the rather long time to extubation may be explained perhaps by reduced clearance of propofol in preterm infants in the first 10 days of life which leads to longer duration of the sedative effect. Dose-finding studies in preterm infants of different gestational and postnatal ages should be performed to determine the appropriate dose of propofol for different gestational and postnatal ages.