An investigation of the efficacy and safety of remifentanil for the provision of optimal sedation in adult ICU patients requiring short-term mechanical ventilation: preliminary results

Introduction

Remifentanil HCl is a μ-opioid agonist which has an onset of action of about 1 min and rapidly achieves steady-state. Metabolism by non-specific blood and tissue esterases results in a terminal half-life of < 10 min which is independent of the duration of infusion.

Methods

In this randomised trial, 152 ICU patients (post-cardiac surgical [60%], post-general surgical [34%], medical [6%]) without significant renal dysfunction received an initial infusion of either remifentanil (9 μg/kg/h) or fentanyl (1 μg/kg bolus + 1.5 μg/kg/h) in a double-blind manner. Optimal sedation, defined as a Sedation Agitation Scale (SAS) score of 4 (patient was calm, and easily arousable), with no or mild pain was achieved by initial titration of the opioid infusion (fentanyl patients also received bolus doses of 1 μg/kg) followed by administration of propofol (0.5 mg/kg/h), if required, according to a pre-defined dosing algorithm specifically designed to reflect the advantages that the study drug offered. Assessments of SAS, pain intensity, mean arterial pressure and heart rate were made every 20 min for the first 6 hours after starting the opioid infusion and then hourly.

Results

See Table.

Table 1

Conclusions

The dosing algorithm allowed effective provision of optimal sedation with remifentanil without the addition of propofol in the majority of patients. The similarity of the results for fentanyl probably reflects the stringent conditions of the dosing algorithm, which demanded frequent monitoring and adjustment of the level of sedation to ensure that a SAS score of 4 was maintained. The remifentanil regimen was well tolerated and the safety profile was similar to fentanyl. The titratability and predictable duration of action make remifentanil a very effective opioid for the provision of analgesia/sedation in ICU patients.

This study (USA30206) was supported by a grant from Glaxo Wellcome.