Ellen de Kort

155 General discussion 9 The majority of studies investigating the combination of a vagolytic, an analgesic and a muscle relaxant, used fentanyl as the analgesic. 34,44-46,50 The choice for fentanyl is based on its fast speed of onset and its cardiovascular stability. There are no clear guidelines as to the dose of fentanyl that should be used to provide sufficient analgesia for this purpose, and the fentanyl dose that was used differed across studies. 34,44,46,50 Data on the pharmacodynamic effects of fentanyl as premedication for endotracheal intubation are not available. It is, therefore, unclear how much fentanyl should be administered to eliminate the pain and discomfort that accompany the act of laryngoscopy. More research into the effects of fentanyl for this purpose is needed, but when administered as part of a premedication strategy also containing a muscle relaxant, this is difficult to examine because paralysis has a clear influence on the behavioral responses to pain. Chest wall rigidity is one of the most frequent and serious complications of fentanyl. In the neonatal population, the risk of chest wall rigidity after fentanyl administration has been estimated at 1.4 to 4%. 51,52 More recent studies did find comparable incidences. 34,45 Chest wall rigidity can be prevented by slow infusion, and can be treated with the use of a muscle relaxant or naloxone, 32 the latter obviously also abolishing the analgesic effect of fentanyl. Dempsey et al. used a strategy in which the muscle relaxant was administered prior to fentanyl to prevent chest wall rigidity, and indeed this side effect did not appear in their study population. 46 The use of a muscle relaxant prior to an analgesic, however, causes the patient to be conscious while being paralyzed and raises ethical questions. Over the past decade, interest arose into single drug premedication strategies with a short duration of action. Based on its rapid onset of action and very short half-life, remifentanil seemed a suitable candidate in this perspective. Four studies have used different doses of remifentanil as a single drug and found conflicting results both on sedative effect and on the occurrence of side effects. A remifentanil dose of 2 μg/kg was found to cause adequate sedation in all patients in one study, while two studies found doses of 1 μg/kg and 3 μg/kg to cause insufficient sedation in one third of study patients. 50,53,54 In our observational study we found that both with starting doses of 1 μg/kg and 2 μg/kg adequate sedation was very difficult to achieve. 55 Welzing et al. did not observe chest wall rigidity in their patient population and both Avino et al. and Choong et al. found low incidences of 6% and 13% respectively. 50,53,54 We found a much higher incidence of 43%. 55 The dramatic results in our study could be attributed to the fast infusion rate of 30 seconds, causing a shorter duration of effect and higher peak levels with more side effects as a consequence. But even with a more appropriate infusion rate of 60 seconds, the results of several of the abovementioned studies raise concerns about effectivity as well as safety of remifentanil as premedication in the neonatal population. Dose-finding studies are clearly needed to address these issues.