Remifentanil versus fentanyl for analgesia based sedation to provide patient comfort in the intensive care unit: a randomized, double-blind controlled trial [ISRCTN43755713]

Bernd Muellejans¹ , Angel López², Michael H Cross³, César Bonome⁴, Lachlan Morrison⁵ and Andrew JT Kirkham⁶

¹Director of Anaesthesiology & Intensive Care Medicine, Klinikum Karlsburg, Herz-und Diabeteszentrum Mecklenburg-Vorpommern Klinik für Anaesthesiologie und Intensivmedizin, Karlsburg, Germany

²Consultant Anaesthesiologist, Servicio de Medicina Intensiva, Hospital Universitario Infanta Cristina, Badajoz, Spain

³Consultant Anaesthetist, Department of Anaesthesia, Leeds General Infirmary, Leeds, UK

⁴Attending Staff, Department of Anaesthesiology, Hospital Juan Canalejo, Servicio de Anestesiologia y Reanimación, La Coruña, Spain

⁵Consultant in Anaesthetics and Intensive Care, Department of Anaesthesia, St. John's Hospital, Livingston, UK

⁶Global Study Manager, GlaxoSmithKline Research and Development, Greenford, UK

author email corresponding author email

Critical Care 2004, 8:R1-R11doi:10.1186/cc2398


Published:	20 November 2003

See related Commentary: http://ccforum.com/content/8/1/13

Abstract

Introduction

This double-blind, randomized, multicentre study was conducted to compare the efficacy and safety of remifentanil and fentanyl for intensive care unit (ICU) sedation and analgesia.

Methods

Intubated cardiac, general postsurgical or medical patients (aged ≥ 18 years), who were mechanically ventilated for 12–72 hours, received remifentanil (9 μg/kg per hour; n = 77) or fentanyl (1.5 μg/kg per hour; n = 75). Initial opioid titration was supplemented with propofol (0.5 mg/kg per hour), if required, to achieve optimal sedation (i.e. a Sedation–Agitation Scale score of 4).

Results

The mean percentages of time in optimal sedation were 88.3% for remifentanil and 89.3% for fentanyl (not significant). Patients with a Sedation–Agitation Scale score of 4 exhibited significantly less between-patient variability in optimal sedation on remifentanil (variance ratio of fentanyl to remifentanil 1.84; P = 0.009). Of patients who received fentanyl 40% required propofol, as compared with 35% of those who received remifentanil (median total doses 683 mg and 378 mg, respectively; P = 0.065). Recovery was rapid (median time to extubation: 1.1 hours for remifentanil and 1.3 hours for fentanyl; not significant). Remifentanil patients who experienced pain did so for significantly longer during extubation (6.5% of the time versus 1.4%; P = 0.013), postextubation (10.2% versus 3.6%; P = 0.001) and post-treatment (13.5% versus 5.1%; P = 0.001), but they exhibited similar haemodynamic stability with no significant differences in adverse event incidence.

Conclusion

Analgesia based sedation with remifentanil titrated to response provided effective sedation and rapid extubation without the need for propofol in most patients. Fentanyl was similar, probably because the dosing algorithm demanded frequent monitoring and adjustment, thereby preventing over-sedation. Rapid offset of analgesia with remifentanil resulted in a greater incidence of pain, highlighting the need for proactive pain management when transitioning to longer acting analgesics, which is difficult within a double-blind study but would be quite possible under normal circumstances.