Remifentanil-induced pronociceptive effect and its prevention with pregabalin

BACKGROUND: Experimental and clinical studies have suggested that remifentanil probably causes acute tolerance or postinfusion hyperalgesia. This study was designed to confirm whether remifentanil given during propofol anesthesia induced postoperative pain sensitization, and we wanted to investigate whether pregabalin could prevent this pronociceptive effect. METHODS: Sixty patients who were scheduled for total abdominal hysterectomy were randomly allocated to receive (1) a placebo as premedication and an intraoperative saline infusion (control group), (2) a placebo as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (remifentanil group), or (3) pregabalin 150 mg as premedication and an intraoperative infusion of remifentanil at a rate of 3-4 ng/ml (pregabalin-remifentanil group). Postoperative pain was controlled by titration of fentanyl in the postanesthetic care unit (PACU), followed by patient-controlled analgesia (PCA) with fentanyl. The patients were evaluated using the visual analogue scale (VAS) for pain scores at rest and after cough, consumption of fentanyl, sedation score and any side effects that were noted over the 48 h postoperative period. RESULTS: The fentanyl titration dose given in the PACU was significantly larger in the remifentanil group as compared with those of the other two groups. At rest, the VAS pain score in the remifentanil group at 2 h after arrival in the PACU was significantly higher than those in the other two groups. CONCLUSIONS: The results of this study show that remifentanil added to propofol anesthesia causes pain sensitization in the immediate postoperative period. Pretreatment with pregabalin prevents this pronociceptive effect and so this may be useful for the management of acute postoperative pain when remifentanil and propofol are used as anesthetics.