An investigation of the offset of pharmacodynamic effects of remifentanil following prolonged infusion in ICU patients with varying degrees of renal dysfunction: preliminary results

Introduction

Remifentanil HCl (R) is a mu-opioid agonist with a rapid onset (∝ 1 min) and offset of action (t1/2 < 10 min) due to its organ-independent metabolism by non-specific tissue and blood esterases. These properties make it readily titratable and even after prolonged infusion the effects of R do not accumulate. Its major metabolite, remifentanil acid (RA) is eliminated by the kidneys and its elimination is prolonged as a result of increasing renal dysfunction. However RA has been reported to have 1/4600 mu-opioid potency of the parent compound. This study assessed the offset of pharmacodynamic (PD) effects of R in ICU patients with varying degrees of renal dysfunction receiving R for provision of sedation and analgesia.

Methods

R (starting rate 6–9 μg/kg/h) was administered as a continuous infusion for up to 72 hours in 40 ICU patients (10 normal/mild renal impairment, creatinine clearance ≥ 50 ml/min: 30 moderate/severe renal impairment, creatinine clearance <50 ml/min) who required sedation and analgesia. At scheduled times (8, 24, 48 and 72 hours) R was down titrated until the offset of PD effects (eg changes in sedation, pain intensity, respiratory function or haemodynamic variables) were seen. On confirmation of the offset of PD effects, R was continued at the original rate.

Results

See Table.

Table

Conclusions

The offset of the PD effects of R were consistent and independent of the duration of infusion even in patients with a significant degree of renal dysfunction. R was well tolerated in these patients. R may therefore be an ideal agent for provision of sedation and analgesia to patients with varying degrees of renal dysfunction in the ICU.

This study (USA30212) was supported by a grant from Glaxo Wellcome.