Effects of Pregabalin on Intravenous Sedation Using Propofol Target-controlled Infusions

1.Statement of the problem: In recent dental/oral surgery including dental implant treatment, intravenous (IV) sedation is the effective method for pain and anxiety control. The perioperative stability of the cardiovascular system and the respiratory system is also an important element of IV sedation. Propofol and benzodiazepines are often used as the sedative drugs in IV sedation; however, they sometimes cause blood pressure reduction and respiratory depression. Furthermore, these agents have no satisfactory analgesic actions. Pregabalin (gabapentinoid) is often used as the drug of first alternative in the treatment of neuropathic pain. It has been reported that premedication of oral pregabalin reduces the postoperative pain¹⁾ and increases the perioperative sedation level²⁾. However, there is not enough evidence to characterize the influence of pregabalin on the interaction with the IV anesthetics. In this study, we investigated the sedative and analgesic effects of pregabalin administered orally on IV sedation using propofol target-controlled infusions.

 2. Materials and methods: After the approval of the research ethics committee and written informed consent had been obtained, 6 healthy ASA Physical Status 1 volunteers (2 male and 4 female, 23–32 years old) were studied in a cross-over design. Each subject underwent 1 hour of IV sedation using propofol three times on the separate days: first placebo, second pregabalin 100 mg and third pregabalin 200 mg. Each dose of pregabalin was administered orally 1 hour before the IV sedation. The blood concentration of propofol was increased gradually with target-controlled-infusion until the BIS-value reached 60. Under the deep sedation, we applied an injection of normal saline 1.8 ml into the maxillary oral vestibule as a pain stimulus. The primary endpoint was the blood concentration of propofol at the BIS-value of 60 and the secondary endpoints were Ramsay’s sedation score at each blood concentration of propofol, circulatory and respiratory dynamics, the body movement and arousal at the pain stimulus, vascular pain caused by propofol infusion and side effects. Vascular pain score was evaluated by Visual-Analogue-Scale.

3. Methods of data analysis: Data are presented as mean ± standard deviation (SD). Results were tested with analysis of variance (ANOVA), which was followed with Dunnett’s test. The occurrence rates of side effects were analyzed with Fisher’s exact Test. Differences were considered significant when P<0.05.

4. Results: Oral pregabalin (100 mg and 200 mg) reduced the blood concentration of propofol at the BIS-value of 60 in comparison with control. Ramsay’s sedation scores at the propofol blood concentration of 0.5 µg/ml and 1.2 µg/ml were significantly higher in the pregabalin 200 mg group compared with control. Circulatory and respiratory dynamics had no significant differences between the groups. Pregabalin failed to affect the hemodynamic response and the arousal level caused by the pain stimulus. However, body movement at the pain stimulus tended to be decreased with pregabalin. Vascular pain caused by propofol injection tended to be reduced by oral administration of pregabalin. In the pregabalin groups, postanesthetic nausea, dizziness and drowsiness were significantly higher than control.

5. Conclusions: In the IV sedation using propofol, premedication of oral pregabalin may be effective to reduce the amount of propofol needed to obtain the adequate sedation level. On the other hand, it is necessary to take measures to prevent the postanesthetic side effects of pregabalin such as nausea, dizziness and drowsiness.

6. References: 1) O. Mathiesen et al. Pregabalin and dexamethasone improves post-operative pain treatment after tonsillectomy. Acta Anaesthesiol Scand. 2011; 55: 297–305. 2) Paul F. White et al. The effect of pregabalin on preoperative anxiety and sedation levels: A dose ranging study. Anesth Analg. 2009; 108: 1140–1145.