Ellen de Kort

34 Chapter 2 Further concerns about propofol in pretermneonates include the relatively high incidence of side effects, especially profound hypotension. The pilot study of Welzing et al. was stopped prematurely because of significant hypotension in five patients. 17 The relatively long-lasting sedation and high incidence of hypotension point at excessive propofol doses. Evidence on the hypotensive side effect of propofol is not consistent: some studies report relatively high frequencies of hypotension, 40,44-46 but this is not confirmed by others. 12,31,47 Vanderhaegen et al. studied the cerebral and systemic hemodynamic effects of propofol in neonates and found a short lasting decrease in cerebral oxygenation of several minutes and a decrease in mean arterial blood pressure up to 1 hour after propofol administration. 40 Possible age-related propofol dose response of neonates needs further exploration. The adequate propofol doses that provide good sedation, no hypotension or decreased cerebral perfusion, and fast restoration of sufficient breathing have yet to be found. Also, more research into the adequate doses of propofol for different gestational age groups during the INSURE procedure is needed. Once known, propofol should be compared with remifentanil in a randomized controlled manner, to evaluate which drug would be best with the fewest side effects. Of all other 10 publications describing the INSURE procedure, only the one by Cherif et al. on morphine reported a time to extubation, that is 6.3 ± 1.7 minutes (range 5–12 minutes). 20 Based on the PK/PD profile of morphine in newborns this seems to be quite short and morphine might not even have reached maximum concentration, also in view of the fact that INSURE failed in 32% of patients. This may have been due to recurrent apnea due to opioid induced respiratory depression. All other nine studies did not mention time to awakening and extubation but some of the studies mentioned INSURE failure because of intractable apneas. 19,21,23,24,26 Opioid induced respiratory depression probably was the cause of these apneas. Morphine has several limitations, notably delayed onset and prolonged duration of action, on account ofwhich it is unsuitable to be used as a sedative in neonatal intubation. 6,11,36 This is confirmed by several studies. Lemyre et al. performed a randomized placebo controlled trial of morphine and found no differences between morphine and placebo in duration of distortion of vital parameters, duration of the intubation procedure, and number of attempts. 48 Several other studies comparedmorphinewith other premedication regimens and unanimously found that morphine was less effective, providing worse intubation conditions and necessitating a greater number of attempts. 12,36,49 The prolonged duration of action of morphine could be antagonized with naloxone. However, naloxone also antagonizes endorphins and results in a direct very distressful condition and has the potential to cause cardiac arrest, as reported in an extremely preterm infant and two adult patients. 50 Also, the duration of action of naloxone is much shorter than that of morphine.