Ellen de Kort

159 General discussion 9 Rather than focusing on a single premedication strategy that is used within the entire neonatal population, the course should be changed towards a more personalized approach. In the choice for the most suitable premedication strategy, factors such as gestational age and postnatal age, underlying illness, reason for intubation, hemodynamic stability and expected duration of mechanical ventilation should all be considered. In a patient that is being intubated for the purpose of mechanical ventilation for at least several hours, the use of premedication with a very short period of action is probably less important. In these patients, a combination of fentanyl and a short-acting muscle relaxant seems the most appropriate strategy. Propofol should not be used in patients with hemodynamic instability, and probably also in patients who are being at risk for developing hemodynamic instability, such as patients with a sepsis or necrotizing enterocolitis. In these patients, fentanyl in combination with a short-acting muscle relaxant is probably a more appropriate choice. Although muscle relaxants can improve intubation conditions and first attempt success rates, and decrease the incidence of hypoxic events, the use of a muscle relaxant should be carefully considered in every individual patient. Muscle relaxants cause paralysis, also in the respiratory muscles, with subsequent cessation of spontaneous breathing. This is not desirable in every patient or even contraindicated in some categories of patients. This concerns patients with a known or anticipated difficult airway, in whom maintaining a spontaneous breathing pattern is of utmost importance in case of failed intubation and possible difficulty with bag and mask ventilation. Also, in patients with severe respiratory failure, diaphragmatic paralysis due to the use of a muscle relaxant can impair pulmonary function, thereby seriously worsening the course of the disease. In these patients, propofol could be used, provided that the hemodynamic condition is stable. In case of hemodynamic instability in a patient with a known or anticipated difficult airway, both fentanyl and remifentanil as single drug regimens could be considered. However, both should be used with caution with specific attention to the prevention of chest wall rigidity, because this often needs treatment with a muscle relaxant that hampers the respiratory drive. A significant proportion of drugs in the neonatal intensive care unit is used off label and there are only a limited number of clinical trials on efficacy, dosage and safety of drugs in the neonatal population. 78 This lack of knowledge results in different drug therapies in clinical practice. 79 This certainly applies to the different drugs that are used as premedication for endotracheal intubation in neonates. Information on dosing of these drugs is lacking and doses for the neonatal population are often extrapolated from data in older children and adults. Dose-finding studies in large populations of neonates with clear definitions of effect and side effects are urgently needed to resolve this issue. These studies are, however, difficult to perform. Our NEOPROP-2 trial demonstrates the difficulties that could be encountered when performing such dose-finding trials. Our study had to be