Preoperative Pregabalin and the Cp50 for Skin Incision During Target-Controlled Propofol Infusion: A Randomized, Placebo-Controlled, Double-Blind Clinical Trial.

Abstract

The potency of propofol is measured by its Cp50 value, which is the plasma concentration required to suppress a motor response in 50% of patients during surgical incisions. This Cp50 value can be affected by the concurrent use of other drugs, including opioids, benzodiazepines, or lidocaine. Pregabalin, a medication commonly administered as preoperative premedication, provides mild sedative and anxiolytic effects. Although pregabalin has the potential to reduce the minimum alveolar concentration (MAC) of sevoflurane, its effects on propofol-based anesthesia have not been conclusively studied. Thus, we designed a placebo-controlled, double-blind clinical trial to evaluate the impact of pregabalin on the Cp50 of propofol. Eighty female patients who underwent breast surgery participated in this study. They received either a placebo or 300 mg of pregabalin 2 hours before anesthesia induction. Propofol was administered as the sole anesthetic agent, delivered continuously via a target-controlled infusion (TCI) pump using the Schnider model, without the addition of opioids or other analgesics. Patients in both groups were administered different target effect-site propofol concentrations, and their motor responses to standardized skin incisions were determined. The Cp50 value of propofol was estimated using a logistic regression model, and the results were re-evaluated using bootstrap methods. A significant difference in propofol Cp50 values was found between the placebo and pregabalin groups. Using the delta method, the Cp50 value of propofol was estimated to be 16.9 μg/mL (95% confidence interval [CI], 15.1-18.8) in the placebo group and 9.4 μg/mL (95% CI, 4.46-14.3) in the pregabalin group. Secondary outcome measures revealed significantly decreased opioid consumption and pain levels in the recovery area in the pregabalin group compared to the placebo group. This study demonstrated that pretreatment with 300 mg pregabalin significantly reduced the Cp50 value of propofol by 44%, as calculated using the delta method. When 300 mg of pregabalin is administered before anesthesia and propofol is used for maintenance via TCI, a lower target effect-site concentration might be sufficient. Additionally, pregabalin premedication has the potential to decrease postoperative pain and opioid consumption.