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

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 microgram/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.

Figure 1

Mean (± 95% confidence interval) time to offset of the pharmacodynamic effects of remifentanil at 8, 24, 48 and 72 hour scheduled down-titrations (SDTs), analyzed using the Cox proportional hazards model. (a) Group with normal/mild renal impairment. Numbers included at each assessment were as follows: 10 at the 8 hour SDT, 10 at the 24 hour SDT, eight at the 48 hour SDT, and six at the 72 hour SDT. (b)Group with moderate/severe renal impairment. Numbers included at each assessment were as follows: 28 at the 8 hour SDT, 25 at the 24 hour SDT, 15 at the 48 hour SDT, and 15 at the 72 hour SDT. P values are as follows (all versus group with normal/mildly impaired renal function): 0.616 at the 8 hour SDT, 0.031 at the 24 hour SDT, 0.998 at the 48 hour SDT, and 0.042 at the 72 hour SDT.

Figure 2

Scatter plot of time to the offset of pharmacodynamic (PD) effects versus remifentanil acid concentrations at the start of down-titration.