Intensive Care Medicine

, Volume 38, Issue 6, pp 1017–1024 | Cite as

Remifentanil/midazolam versus fentanyl/midazolam for analgesia and sedation of mechanically ventilated neonates and young infants: a randomized controlled trial

  • Lars WelzingEmail author
  • Andre Oberthuer
  • Shino Junghaenel
  • Urs Harnischmacher
  • Hartmut Stützer
  • Bernhard Roth
Pediatric Original



Common opioids for analgesia and sedation of mechanically ventilated infants may tend to accumulate and cause prolonged sedation with an unpredictable extubation time. Remifentanil is a promising option due to its unique pharmacokinetic properties, which seem to be valid in adults as well as in infants.


In this double-blind, randomized, controlled trial mechanically ventilated neonates and young infants (<60 days) received either a remifentanil or fentanyl-based analgesia and sedation regimen with low dose midazolam. The primary endpoint of the trial was the extubation time following discontinuation of the opioid infusion. Secondary endpoints included efficacy and safety aspects.


Between November 2006 and March 2010, we screened 431 mechanically ventilated infants for eligibility. The intention to treat group included 23 infants who were assigned to receive either remifentanil (n = 11) or fentanyl (n = 12). Although this was designed as a pilot study, median extubation time was significantly shorter in the remifentanil group (80.0 min, IQR = 15.0–165.0) compared to the fentanyl group (782.5 min, IQR = 250.8–1,875.0) (p = 0.005). Remifentanil and fentanyl provided comparable efficacy with more than two-thirds of the measurements indicating optimal analgesia and sedation (66.4 and 70.2 %, respectively; p = 0.743). Overall, both groups had good hemodynamic stability and a comparably low incidence of adverse events.


As neonates and young infants have a decreased metabolism of common opioids like fentanyl and are more prone to respiratory depression, remifentanil could be the ideal opioid for analgesia and sedation of mechanically ventilated infants.


Mechanically ventilated infants Analgesia and sedation Remifentanil Efficacy Safety Extubation time 



This study was supported by a grant from GlaxoSmithKline (Munich, Germany) and by departmental sources. GlaxoSmithKline had no influence on study design, data analysis, or writing of the manuscript. The sponsor of the clinical trial, in accordance with Good Clinical Practice, was the University of Cologne.


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Copyright information

© Copyright jointly held by Springer and ESICM 2012

Authors and Affiliations

  • Lars Welzing
    • 1
    Email author
  • Andre Oberthuer
    • 1
  • Shino Junghaenel
    • 1
  • Urs Harnischmacher
    • 2
  • Hartmut Stützer
    • 3
  • Bernhard Roth
    • 1
  1. 1.Department of Neonatology and Paediatric Intensive Care, Childrens HospitalUniversity Hospital of CologneCologneGermany
  2. 2.Clinical Trials Center Cologne (ZKS Koeln, BMBF 01KN1106)University of CologneCologneGermany
  3. 3.Institute of Medical Statistics, Informatics and EpidemiologyUniversity Hospital of CologneCologneGermany

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