A Randomized Placebo Controlled Study of Preoperative Pregabalin on Postcholecystectomy Pain Relief

Abstract

There are studies that have demonstrated the role of pregabalin as a pre-emptic analgesic in the multimodal therapy for acute postoperative pain management. However, its use in more painful operative procedures like open cholecystectomy are limited and hence the present study was undertaken to evaluate the effectiveness of a single dose of preoperative oral pregabalin in attenuating the postoperative pain. In this randomized, controlled, prospective and double blind study, 80 patients (ASA I & II, aged 18-55 years and of both sexes) undergoing open cholecystectomy under GA were divided into two equal groups (n=40 each) to receive either oral pregabalin 150mg or placebo 1 hour before the surgery. Intraoperative hemodynamic variables, postoperative VAS scores, sedation scores, analgesic free time intervals, total dose of rescue analgesic, side effects etc. were recorded and compared for the first 24 hours postoperatively. VAS score distribution in the first 24 hours were significantly lower in the pregabalin group than the control group (P<0.05). The analgesia free time interval was longer and the number of rescue analgesic(inj. tramadol 50mg) was lesser in the pregabalin 150mg (P<.05). Preoperative pregabalin 150 mg administered 1 hour prior to surgery attenuates the postoperative pain thereby reducing opioid consumption. KEYWORDS:Pregabalin, open cholecystectomy, pre-emptic analgesia and postoperative pain. INTRODUCTION:Post-operative pain is the most common clinical problem in hospitals among surgical patients and is the main reason for overnight hospital stay in17-41% of surgical day care patients. 1 It has been managed with varieties of drugs and techniques such as combination of opioids, non-steroidal anti-inflammatory drugs (NSAIDS) or paracetamol, small dose ketamine, peri-operative administration of local anesthetics, interventional techniques like epidural and nerve blocks etc. which are associated with potential risks of serious complications. Thus, with the emerging concepts of pre-emptive analgesia, a drug that has analgesic properties, opioid sparing effects, possibly reduces opioid tolerance, relieves anxiety and is not associated with adverse effects typical for the traditional analgesic would be an attractive adjuvant for post-operative pain management. 2 Pregabalin and its developmental predecessor gabalin were originally developed as spasmolytic agents and adjuncts for the management of generalized or partial epileptic seizures resistant to conventional therapies. Pregabalin, like gabapentin is an amino-acid derivative of gamma amino butyric acid. It binds to the α2-δ (type I) receptor in the central nervous system. Binding of pregabalin to the α2-δ (type I) subunit of voltage gated calcium channels alter the kinetic and voltage dependence of calcium current. By reducing calcium influx at the nerve terminal pregabalin reduces the release of several neurotransmitters including glutamate, substance-P, noradrenaline and calcitonin gene related peptide. This accounts for the analgesic activity of pre...

Evaluation of Preoperative Anxiolytic and Postoperative Analgesic Effects of Pregabalin Premedication

“…33 Many studies assessing preoperative 150 mg pregabalin efficacy on postoperative pain after operations performed with different anesthesia and surgical methods have also shown fewer side effects due to reduced opioid consumption. 17,24 As a result of all this information; we reached the conclusion that the preoperative use of Pregabalin 150 mg 12 hours and 1 hour prior to surgery reduced preoperative anxiety, provided postoperative analgesia, reduced analgesic consumption and associated side effects, thus proving to be superior to placebo. However, in order for pregabalin to be used as routine premedication, larger sample groups and studies with different doses are required.…”

“…In response to these studies on the suppressive effect of preoperative pregabalin on hemodynamic parameters, Upendra et al concluded that hemodynamic parameters did not change after preoperative pregabalin 150 mg in their study including 80 patients who underwent cholecystectom. 24 Again, as a result of a prospective, placebo-controlled study including 60 patients with axillary block, Pürcü et al reached the conclusion that pregabalin did not affect hemodynamic parameters after a single dose of preoperative pregabalin 150 mg. 25 In their placebo-controlled studies on the effects of pregabalin 75 mg and 150 mg premedication on hemodynamic responses, Rastogi et al have concluded that the premedication did not result in a clinically significant respiratory depression and reduction in oxygen saturation. 26 In our study, no changes in favor of desaturation in intraoperative peripheral oxygen saturation values were observed in both groups.…”

“…15 In several studies evaluating postoperative pain and analgesic consumption by administering pregabalin 150 mg premedication in different types of surgery under general anesthesia, different researchers have observed that reported that pregabalin reduced postoperative pain and analgesic consumption. 24 In addition to general anesthesia, effects of pregabalin premedication on postoperative pain and opioid consumption has been studied in regional anesthesia applications and it was concluded that pregabalin reduced postoperative pain and analgesic consumption. 25 In their study including 40 patients who underwent prospective placebo-controlled elective thoracotomy, Tunç et al assessed pain scores and epidural opioid use by administering thoracic epidural patient-controlled analgesia to all patients after the use of preoperative 150 mg pregabalin and reached the conclusion that pain scores and epidural opioid consumption decreased.…”