Effects of remifentanil on cognitive and psychomotor functioning and mood

Abstract

Editor'In this double-blind, placebo-controlled, cross-over study, we examined the effects of remifentanil on cognitive and psychomotor function, mood, and subjective feelings, including the exploration of gender differences during a steady-state target-controlled infusion (TCI) of low-dose remifentanil, which has not been reported before. As a potent, ultra-short-acting µ-opioid receptor agonist remifentanil has a unique pharmacokinetic profile which makes it an attractive drug for the study of opioid effects. Our hypothesis was that remifentanil impairs cognitive and psychomotor function and affects subjective feelings and that there might be gender differences in these effects. Twenty healthy volunteers (10 men and 10 women) aged 18–40 yr were included. On two test days, participants received remifentanil or placebo (saline) in a randomized cross-over design. Remifentanil was administered at an effect-site concentration of 1 ng ml−1 using a TCI pump. The dose was chosen from previous fMRI studies which showed an analgesic effect of this dose without excessive sedation or blood oxygen desaturation.1Wise RG Williams P Tracey I Using fMRI to quantify the time dependence of remifentanil analgesia in the human brain.Neuropsychopharmacology. 2004; 29: 626-635Crossref PubMed Scopus (100) Google Scholar Drug effects were measured using a Digit Symbol Substitution Task (DSST), choice reaction time (RT), visual analogue scales (VAS), a Symptom List, and the Profile of Mood States (POMS) questionnaire (Fig. 1). Data were analysed using repeated-measures analysis of variance. Differences with P<0.05 were considered as statistically significant. Remifentanil slowed down psychomotor function as seen in a significantly increased RT (401 vs 373 ms), but did not affect cognitive performance on the DSST. During remifentanil infusion, participants felt more sleepy, confused, dizzy, and had more itchy skin. Women felt sleepier and tended to feel more sad and nauseous than men. On the POMS questionnaire, remifentanil increased vigour, fatigue, and feeling confused in both genders, but had no dysphoric effects on participants. Since cognitive and psychomotor functioning (e.g. memory, attention, visuo-motor coordination) are essential during recovery from sedation and anaesthesia, knowledge of these effects for individual drugs is useful for a clinician, for example, to evaluate the home-readiness of patients. In addition, remifentanil caused sedation, fatigue, and confusion in participants, but at the same time, they felt more vigour. Women felt stronger sedated and had more side-effects than men. Approximately 30 min after remifentanil infusion as the TCI reached an effect-site concentration of 0.0 ng ml−1, participants still felt dizzy [VAS score 2.95 (1.0) mm, P=0.007], but all other subjective feelings had returned to baseline. None declared.