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

Breen Des, Wilmer Alexander, Bodenham Andrew, Bach Vagn, Bonde Jan, Kessler Paul, Albrecht Sven, Shaikh, Shaikh Soraya

Description

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.

Sujets

• Critical care
• Pharmacodynamics
• Rémifentanil
• Renal function
• SAFETY

Informations

• Publié par: biomed
• Publié le: 01 janvier 2003
• Nombre de lectures: 169
• Langue: English

Extrait

Available onlinehttp://ccforum.com/content/8/1/R21

Open Access Research Offset of pharmacodynamic effects and safety of remifentanil in intensive care unit patients with various degrees of renal impairment 1 23 45 6 Des Breen, Alexander Wilmer, Andrew Bodenham, Vagn Bach, Jan Bonde, Paul Kessler, 7 8 Sven Albrechtand Soraya Shaikh

1 Consultant in Anaesthesia and Intensive Care, ICU, Royal Hallamshire Hospital, Sheffield, UK 2 Associate Professor of Medicine, MICU, UZ Gasthuisberg, Leuven, Belgium 3 Consultant in Anaesthesia and Intensive Care, ICU, Leeds General Infirmary, Leeds, UK 4 Director of Intensive Care, Hillerod Syngehus, Hillerod, Denmark 5 Consultant in Intensive Care, Amtssygehuset i Herlev, Herlev, Denmark 6 Assistant Professor of Anaesthesiology, ICU, JW Goethe Universitat, Klinik fuer Anaesthesiologie, Frankfurt, Germany 7 Professor and Vice Chairman, ICU, Universitat ErlangenNurnberg, Klinik fur Anaesthesiologie, Erlangen, Germany 8 Global Study Manager, GlaxoSmithKline R&D, Greenford, UK

Correspondence: Des Breen, [e-mail]

Received: 2 October 2003

Accepted: 16 October 2003

Published: 21 November 2003

Critical Care2004,8:R21R30 (DOI 10.1186/cc2399) This article is online at http://ccforum.com/content/8/1/R21 © 2004 Breenet al., licensee BioMed Central Ltd (Print ISSN 13648535; Online ISSN 1466609X). This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

Abstract IntroductionThis 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. MethodsA 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 72hours (initial rate 6–9µg/kg per hour), with propofol administered if required, to achieve a target Sedation–Agitation Scale score of 2–4, with no or mild pain. ResultsThere 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 24hours and 72hours. 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. ConclusionRemifentanil 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.

Keywordsanalgesia based sedation, critical care, offset times, pharmacodynamics, remifentanil, renal function, safety

CL =creatinine clearance; HR = heart rate; ICU = intensive care unit; MAP = mean arterial pressure; PI = Pain Intensity (scale); RR = respiratory cr rate; SAE = serious adverse event; SAPS = Simplified Acute Physiology Score; SAS = Sedation–Agitation Scale; SDT = scheduled downtitration. R21