Rapip Study: Clinical Trial on Remifentanyl for Analgesia and Sedation of Ventilated Neonates and Infants

"Newborns (≥ 36 weeks of gestation) and young infants (≤ 60 days) with need of mechanical ventilation receive next to midazolam either remifentanyl or fentanyl for analgesia and sedation. The study medication will be started not later than 12 hours after intubation and the maximum application time is 96 hours. The opioid infusion rate is started with either 9µg/kg/h remifentanyl or 3µg/kg/h fentanyl and will be adapted according to a clinical sedation score (Hartwig- and Comfort score). The maximum infusion rate is 30µg/kg/h remifentanyl or 10µg/kg/h fentanyl.

To judge the efficacy of both opioids, we will evaluate the sedation scores every 6 hours and measure the skin conductance during a painful procedure (tracheal suctioning). Next to the adverse events we document different vital parameters like heart rate, blood pressure or oxygen saturation every 6 hours to estimate the safety of both opioids.

The midazolam plasma level will be determined immediately before termination of the opioid and midazolam infusion when the child is clinically judged to be ready for extubation. The child will be extubated as soon as it reaches a certain level in the sedation score and exhibits stable spontaneous breathing.

After extubation we will look in both treatment groups for the possible development of hyperalgesia by investigating the cutaneous flexor reflex with von Frey hairs. The trial ends for each patient 48 hours after extubation.

Inclusion criteria

• Ventilated term newborns and infants ≤ 60 days
• Expected time of artificial ventilation between 12 and 96 hours

Exclusion criteria

• Neuromuscular diseases
• Drug abuse of the mother (exclusion criteria for newborns)
• Known hypersensitivity to Ultiva® or Fentanyl-Janssen®
• Missing informed consent of the parents
• Participation in another clinical trial during the last 4 weeks before start of this trial