Research

Offset of pharmacodynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment

Des Breen¹ , Alexander Wilmer², Andrew Bodenham³, Vagn Bach⁴, Jan Bonde⁵, Paul Kessler⁶, Sven Albrecht⁷ and Soraya Shaikh⁸

¹Consultant in Anaesthesia and Intensive Care, ICU, Royal Hallamshire Hospital, Sheffield, UK

²Associate Professor of Medicine, MICU, UZ Gasthuisberg, Leuven, Belgium

³Consultant in Anaesthesia and Intensive Care, ICU, Leeds General Infirmary, Leeds, UK

⁴Director of Intensive Care, Hillerod Syngehus, Hillerod, Denmark

⁵Consultant in Intensive Care, Amtssygehuset i Herlev, Herlev, Denmark

⁶Assistant Professor of Anaesthesiology, ICU, J-W Goethe Universitat, Klinik fuer Anaesthesiologie, Frankfurt, Germany

⁷Professor and Vice Chairman, ICU, Universitat Erlangen-Nurnberg, Klinik fur Anaesthesiologie, Erlangen, Germany

⁸Global Study Manager, GlaxoSmithKline R&D, Greenford, UK

author email corresponding author email

Critical Care 2004, 8:R21-R30doi:10.1186/cc2399

Published:	21 November 2003

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

Abstract

Introduction

This open label, multicentre study was conducted to assess the times to offset of the pharmacodynamic effects and the safety of remifentanil in patients with varying degrees of renal impairment requiring intensive care.

Methods

A total of 40 patients, who were aged 18 years or older and had normal/mildly impaired renal function (estimated creatinine clearance ≥ 50 ml/min; n = 10) or moderate/severe renal impairment (estimated creatinine clearance <50 ml/min; n = 30), were entered into the study. Remifentanil was infused for up to 72 hours (initial rate 6–9 μg/kg per hour), with propofol administered if required, to achieve a target Sedation–Agitation Scale score of 2–4, with no or mild pain.

Results

There was no evidence of increased offset time with increased duration of exposure to remifentanil in either group. The time to offset of the effects of remifentanil (at 8, 24, 48 and 72 hours during scheduled down-titrations of the infusion) were more variable and were statistically significantly longer in the moderate/severe group than in the normal/mild group at 24 hours and 72 hours. These observed differences were not clinically significant (the difference in mean offset at 72 hours was only 16.5 min). Propofol consumption was lower with the remifentanil based technique than with hypnotic based sedative techniques. There were no statistically significant differences between the renal function groups in the incidence of adverse events, and no deaths were attributable to remifentanil use.

Conclusion

Remifentanil was well tolerated, and the offset of pharmacodynamic effects was not prolonged either as a result of renal dysfunction or prolonged infusion up to 72 hours.