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Efficacy of pregabalin in acute postoperative pain: a meta-analysis

2011; Elsevier BV; Volume: 106; Issue: 4 Linguagem: Inglês

10.1093/bja/aer027

1471-6771

Jie Zhang, Kok‐Yuen Ho, Ying Wang,

Anesthesia and Sedative Agents

Multimodal treatment of postoperative pain using adjuncts such as gabapentin is becoming more common. Pregabalin has anti-hyperalgesic properties similar to gabapentin. In this systematic review, we evaluated randomized, controlled trials (RCTs) for the analgesic efficacy and opioid-sparing effect of pregabalin in acute postoperative pain. A systematic search of Medline (1966–2010), the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar was performed. We identified 11 valid RCTs that used pregabalin for acute postoperative pain. Postoperative pain intensity was not reduced by pregabalin. Cumulative opioid consumption at 24 h was significantly decreased with pregabalin. At pregabalin doses of <300 mg, there was a reduction of 8.8 mg [weighted mean difference (WMD)]. At pregabalin doses ≥300 mg, cumulative opioid consumption was even lower (WMD, −13.4 mg). Pregabalin reduced opioid-related adverse effects such as vomiting [risk ratio (RR) 0.73; 95% confidence interval (CI) 0.56–0.95]. However, the risk of visual disturbance was greater (RR 3.29; 95% CI 1.95–5.57). Perioperative pregabalin administration reduced opioid consumption and opioid-related adverse effects after surgery. Multimodal treatment of postoperative pain using adjuncts such as gabapentin is becoming more common. Pregabalin has anti-hyperalgesic properties similar to gabapentin. In this systematic review, we evaluated randomized, controlled trials (RCTs) for the analgesic efficacy and opioid-sparing effect of pregabalin in acute postoperative pain. A systematic search of Medline (1966–2010), the Cochrane Central Register of Controlled Trials (CENTRAL), and Google Scholar was performed. We identified 11 valid RCTs that used pregabalin for acute postoperative pain. Postoperative pain intensity was not reduced by pregabalin. Cumulative opioid consumption at 24 h was significantly decreased with pregabalin. At pregabalin doses of <300 mg, there was a reduction of 8.8 mg [weighted mean difference (WMD)]. At pregabalin doses ≥300 mg, cumulative opioid consumption was even lower (WMD, −13.4 mg). Pregabalin reduced opioid-related adverse effects such as vomiting [risk ratio (RR) 0.73; 95% confidence interval (CI) 0.56–0.95]. However, the risk of visual disturbance was greater (RR 3.29; 95% CI 1.95–5.57). Perioperative pregabalin administration reduced opioid consumption and opioid-related adverse effects after surgery. Editor’s key points•Meta-analysis of perioperative pregabalin and postoperative analgesia identified 11 studies.•Pregabalin produced a dose-related reduction in postoperative opioid use.•Pregabalin reduced postoperative nausea and vomiting, but the incidence of visual disturbance was increased.•The diverse nature of the surgery and anaesthetic techniques included suggest that large randomized, controlled trials are still needed. •Meta-analysis of perioperative pregabalin and postoperative analgesia identified 11 studies.•Pregabalin produced a dose-related reduction in postoperative opioid use.•Pregabalin reduced postoperative nausea and vomiting, but the incidence of visual disturbance was increased.•The diverse nature of the surgery and anaesthetic techniques included suggest that large randomized, controlled trials are still needed. Pregabalin is a structural analogue of the inhibitory neurotransmitter γ-aminobutyric acid, but it is not functionally related to it.1Ben-Menachem E Pregabalin pharmacology and its relevance to clinical practice.Epilepsia. 2004; 45: 13-18doi:10.1111/j.0013-9580.2004.455003.xCrossref PubMed Scopus (418) Google Scholar Like its predecessor, gabapentin, it binds to the α-2-δ subunit of voltage-gated calcium channels, reducing the release of several excitatory neurotransmitters and blocking the development of hyperalgesia and central sensitization.2Shneker BF McAuley JW Pregabalin: a new neuromodulator with broad therapeutic indications.Ann Pharmacother. 2005; 39: 2029-2037doi:10.1345/aph.1G078Crossref PubMed Scopus (131) Google Scholar 3Chizh BA Gohring M Troster A Quartey GK Schmelz M Koppert W Effects of oral pregabalin and aprepitant on pain and central sensitization in the electrical hyperalgesia model in human volunteers.Br J Anaesth. 2007; 98: 246-254doi:10.1093/bja/ael344Abstract Full Text Full Text PDF PubMed Scopus (105) Google Scholar Pregabalin has anticonvulsant, anti-hyperalgesic, and anxiolytic properties similar to gabapentin, but it has a more favourable pharmacokinetic profile, including dose-independent absorption.4Guay DR Pregabalin in neuropathic pain: a more ‘pharmaceutically elegant’ gabapentin?.Am J Geriatr Pharmacother. 2005; 3: 274-287doi:10.1016/S1543-5946(05)00084-XAbstract Full Text PDF PubMed Scopus (143) Google Scholar 5Frampton JE Foster RH Pregabalin: in the treatment of postherpetic neuralgia.Drugs. 2005; 65 (discussion 9–20): 111-118doi:10.2165/00003495-200565010-00011Crossref PubMed Scopus (138) Google Scholar It is also several times more potent than gabapentin while producing fewer adverse effects.1Ben-Menachem E Pregabalin pharmacology and its relevance to clinical practice.Epilepsia. 2004; 45: 13-18doi:10.1111/j.0013-9580.2004.455003.xCrossref PubMed Scopus (418) Google Scholar In recent years, pregabalin has been introduced as an adjunct in the multimodal management of postoperative analgesia.6Gilron I Gabapentin and pregabalin for chronic neuropathic and early postsurgical pain: current evidence and future directions.Curr Opin Anaesthesiol. 2007; 20: 456-472doi:10.1097/ACO.0b013e3282effaa7Crossref PubMed Scopus (184) Google Scholar Numerous studies have evaluated the efficacy and adverse effects of pregabalin in reducing acute postoperative pain. However, these studies have yielded conflicting results possibly due to differences in dosage, dosing regimen, and nature of surgery. The aim of this systematic review was to evaluate the available literature on the efficacy of perioperative pregabalin in the management of acute postoperative pain. This review was performed according to the QUOROM guidelines for reporting meta-analyses.7Moher D Cook DJ Eastwood S Olkin I Rennie D Stroup DF Improving the quality of reports of meta-analyses of randomised controlled trials: the QUOROM statement. Quality of Reporting of Meta-analyses.Lancet. 1999; 354: 1896-1900doi:10.1016/S0140-6736(99)04149-5Abstract Full Text Full Text PDF PubMed Scopus (3934) Google Scholar We conducted a literature search of Medline (1966–2010), the Cochrane Central Register of Controlled Trials (CENTRAL 2010), and Google Scholar databases using the following words: ‘pregabalin’, ‘Lyrica’, ‘gabapentinoids’, ‘adjuvants’, ‘postoperative pain’, or ‘surgical-related pain’. Searches were limited to clinical trials and randomized, controlled trials (RCTs) in humans, without language restriction. The last electronic search was performed in April 2010. We also searched the archives of relevant journals by hand to identify additional studies that could meet our inclusion criteria. Additional studies from the bibliographies of reviews or reports were also identified. Authors of original reports were contacted for original data if needed. All randomized, placebo- or active-controlled clinical trials in humans who reported on relevant pain outcomes with intervention or treatment with perioperative pregabalin were included. Abstracts and unpublished observations were not considered. All studies included had a minimum of 10 patients in each study group as recommended by L’Abbe and colleagues.8L’Abbe KA Detsky AS O’Rourke K Meta-analysis in clinical research.Ann Intern Med. 1987; 107: 224-233Crossref PubMed Scopus (1004) Google Scholar Validity of the studies was evaluated using the Modified Oxford Scale (Table 1).9Elia N Tramer MR Ketamine and postoperative pain—a quantitative systematic review of randomised trials.Pain. 2005; 113: 61-70doi:10.1016/j.pain.2004.09.036Abstract Full Text Full Text PDF PubMed Scopus (443) Google Scholar 10Ho KY Gan TJ Habib AS Gabapentin and postoperative pain—a systematic review of randomized controlled trials.Pain. 2006; 126: 91-101doi:10.1016/j.pain.2006.06.018Abstract Full Text Full Text PDF PubMed Scopus (334) Google Scholar Two reviewers scored the studies independently. In the case of discrepancy, a third reviewer was consulted and consensus was reached by discussion. Each study could receive a maximum score of 7. Studies with scores of <3 were considered poor quality and would be excluded from the analysis. Studies with scores of 3–5 were considered fair quality and those with scores of 6 or 7 were considered good-quality studies.Table 1Modified Oxford ScaleScore012RandomizationNoneMentionedDescribed and adequateConcealment of allocationNoneYesDouble blindingNoneMentionedDescribed and adequateFlow of patientsNoneDescribed but incompleteDescribed and adequate Open table in a new tab The following data were collected on the data extraction form: (i) publication details; (ii) quality score of studies; (iii) number of patients; (iv) pregabalin dosage and regimen; (v) study design and duration; (vi) analgesic outcome measures; (vii) adverse effects; and (viii) type of surgery and anaesthesia. The three main outcome measures investigated in this review were pain intensity, total analgesic consumption in the first 24 h after surgery, and adverse effects. Quantitative analysis was performed for 24 h analgesic consumption and pain intensity reported on a visual analogue scale (VAS). Pain intensity was reported at different time points in different studies. However, most studies provided pain scores at 2 and 24 h after operation. To facilitate pooling of data, pain scores at these two time points were analysed as early and late postoperative period. All pain scores on a VAS or Numeric Rating Scale (NRS) were converted to a scale from 0 to 100. Morphine consumption was used as the standard for postoperative opioid consumption. All other opioids used in the studies were converted to equi-analgesic morphine equivalent doses based on the following conversion scale: 100:1 for fentanyl, 1:10 for tramadol, and 1:1.5 for oxycodone. When data were presented graphically, the originals were obtained from the authors or extracted from the graphs if no response was obtained from the authors. Adverse effects including nausea, vomiting, sedation, visual disturbances, dizziness, and headache were noted for analyses. In studies where the study duration was at least 24 h, pain scores and 24 h opioid consumption were quantitatively analysed as weighted mean differences (WMDs) with 95% confidence intervals (CIs). Dichotomous data on adverse effects were summarized using risk ratio (RR) with 95% CI. The random effects model was chosen because of a high clinical heterogeneity among the studies. The significance level was set at 0.05. All analyses were performed using Review Manager Software [Review Manager (RevMan) (Computer program). Version 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008]. Number-needed-to-treat (NNT) or number-needed-to-harm (NNH) was calculated using pooled raw data to estimate the clinical impact of the beneficial or harmful effect of the intervention. The search identified 45 papers on perioperative pregabalin and postoperative pain between 2000 and 2010, but only 17 were relevant (Fig. 1). All reports were published in English. Three were reviews:11Dahl JB Mathiesen O Moiniche S ‘Protective premedication’: an option with gabapentin and related drugs? A review of gabapentin and pregabalin in the treatment of post-operative pain.Acta Anaesthesiol Scand. 2004; 48: 1130-1136doi:10.1111/j.1399-6576.2004.00484.xCrossref PubMed Scopus (233) Google Scholar, 12Dauri M Faria S Gatti A Celidonio L Carpenedo R Sabato AF Gabapentin and pregabalin for the acute post-operative pain management. A systematic-narrative review of the recent clinical evidences.Curr Drug Targets. 2009; 10: 716-733doi:10.2174/138945009788982513Crossref PubMed Scopus (132) Google Scholar, 13Tiippana EM Hamunen K Kontinen VK Kalso E Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety.Anesth Analg. 2007; 104 (table of contents): 1545-1556doi:10.1213/01.ane.0000261517.27532.80Crossref PubMed Scopus (387) Google Scholar one was an animal study related to gabapentinoids,14Field MJ Holloman EF McCleary S Hughes J Singh L Evaluation of gabapentin and S-(+)-3-isobutylgaba in a rat model of postoperative pain.J Pharmacol Exp Ther. 1997; 282: 1242-1246PubMed Google Scholar one was not placebo-controlled,15Freedman BM O’Hara E Pregabalin has opioid-sparing effects following augmentation mammaplasty.Aesthet Surg J. 2008; 28: 421-424Crossref PubMed Scopus (47) Google Scholar and one reported on postoperative chronic pain.16Buvanendran A Kroin JS Della Valle CJ Kari M Moric M Tuman KJ Perioperative oral pregabalin reduces chronic pain after total knee arthroplasty: a prospective, randomized, controlled trial.Anesth Analg. 2010; 110: 199-207doi:10.1213/ANE.0b013e3181c4273aCrossref PubMed Scopus (340) Google Scholar None of the eligible studies was excluded due to poor quality. Therefore, 11 valid randomized, controlled clinical trials with 16 treatment arms were considered for review. The quality of seven of the studies was rated fair17Chang SH Lee HW Kim HK Kim SH Kim DK An evaluation of perioperative pregabalin for prevention and attenuation of postoperative shoulder pain after laparoscopic cholecystectomy.Anesth Analg. 2009; 109: 1284-1286doi:10.1213/ane.0b013e3181b4874dCrossref PubMed Scopus (77) Google Scholar, 18Hill CM Balkenohl M Thomas DW Walker R Mathe H Murray G Pregabalin in patients with postoperative dental pain.Eur J Pain. 2001; 5: 119-124doi:10.1053/eujp.2001.0235Crossref PubMed Scopus (2) Google Scholar, 19Paech MJ Goy R Chua S Scott K Christmas T Doherty DA A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery.Anesth Analg. 2007; 105 (table of contents): 1449-1453doi:10.1213/01.ane.0000286227.13306.d7Crossref PubMed Scopus (108) Google Scholar, 20Jokela R Ahonen J Tallgren M Haanpaa M Korttila K Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery.Br J Anaesth. 2008; 100: 834-840doi:10.1093/bja/aen098Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar, 21Ittichaikulthol W Virankabutra T Kunopart M Khamhom W Putarawuthichai P Rungphet S Effects of pregabalin on post operative morphine consumption and pain after abdominal hysterectomy with/without salphingo-oophorectomy: a randomized, double-blind trial.J Med Assoc Thai. 2009; 92: 1318-1323PubMed Google Scholar, 22Kim SY Jeong JJ Chung WY Kim HJ Nam KH Shim YH Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: a randomized clinical trial.Surg Endosc. 2010; 24: 2776-2781Crossref PubMed Scopus (70) Google Scholar and of five was rated good23Cabrera Schulmeyer MC de la Maza J Ovalle C Farias C Vives I Analgesic effects of a single preoperative dose of pregabalin after laparoscopic sleeve gastrectomy.Obes Surg. 2010; 20: 1678-1681Crossref PubMed Scopus (66) Google Scholar, 24Mathiesen O Jacobsen LS Holm HE et al.Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty.Br J Anaesth. 2008; 101: 535-541doi:10.1093/bja/aen215Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar, 25Mathiesen O Rasmussen ML Dierking G et al.Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial.Acta Anaesthesiol Scand. 2009; 53: 227-235doi:10.1111/j.1399-6576.2008.01821.xCrossref PubMed Scopus (101) Google Scholar, 26Jokela R Ahonen J Tallgren M Haanpaa M Korttila K A randomized controlled trial of perioperative administration of pregabalin for pain after laparoscopic hysterectomy.Pain. 2008; 134: 106-112doi:10.1016/j.pain.2007.04.002Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar, 27Agarwal A Gautam S Gupta D Agarwal S Singh PK Singh U Evaluation of a single preoperative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy.Br J Anaesth. 2008; 101: 700-704doi:10.1093/bja/aen244Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar (Table 2). As two treatment arms in two separate studies had used dexamethasone combined with pregabalin,24Mathiesen O Jacobsen LS Holm HE et al.Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty.Br J Anaesth. 2008; 101: 535-541doi:10.1093/bja/aen215Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar 25Mathiesen O Rasmussen ML Dierking G et al.Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial.Acta Anaesthesiol Scand. 2009; 53: 227-235doi:10.1111/j.1399-6576.2008.01821.xCrossref PubMed Scopus (101) Google Scholar the data from these two arms were not included. Therefore, 14 treatment arms were included in the final analysis. A total of 899 patients were studied, of whom 521 patients received pregabalin.Table 2Randomized, placebo-controlled trials of perioperative pregabalin for acute postoperative pain management. P, pregabalin group; C, control group; NS, no significant difference between groups; preop, before operation; postop, after operation; PCA, patient controlled analgesia; PONV, postoperative nausea and vomiting; GA, general anaesthesia; RA, regional anaesthesia; LA, local anaesthesia; MOS, Modified Oxford ScaleClinical trialMOS scoreNumber of patients (P/C)Dose of pregabalin (mg)Time of pregabalin administrationPain intensity at restPostoperative analgesiaTotal analgesic consumptionTime to first analgesicsAdverse effectsType of surgery and anaesthesiaHill and colleagues18Hill CM Balkenohl M Thomas DW Walker R Mathe H Murray G Pregabalin in patients with postoperative dental pain.Eur J Pain. 2001; 5: 119-124doi:10.1053/eujp.2001.0235Crossref PubMed Scopus (2) Google Scholar399 (two P treatment arms)/5050 and 300PostopP<0.05 in 300 mg groupStudy discontinued if rescue analgesics given——More side-effects in 300 mg P groupMolar extraction, LAPaech and colleagues19Paech MJ Goy R Chua S Scott K Christmas T Doherty DA A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery.Anesth Analg. 2007; 105 (table of contents): 1449-1453doi:10.1213/01.ane.0000286227.13306.d7Crossref PubMed Scopus (108) Google Scholar541/451001 h preopNSI.V. fentanylNS—More light headedness, visual disturbance, and walking difficulty in P groupMinor gynaecological surgery, GAAgarwal and colleagues27Agarwal A Gautam S Gupta D Agarwal S Singh PK Singh U Evaluation of a single preoperative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy.Br J Anaesth. 2008; 101: 700-704doi:10.1093/bja/aen244Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar627/291501 h preopP<0.05I.V. PCA fentanylP<0.05—NSLaparoscopic cholecystectomy, GAJokela and colleagues20Jokela R Ahonen J Tallgren M Haanpaa M Korttila K Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery.Br J Anaesth. 2008; 100: 834-840doi:10.1093/bja/aen098Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar656 (two P treatment arms)/29300 and 6001 h preop and 12 h after first doseNSI.V. PCA oxycodoneP<0.05NSMore blurred vision in both P groups; more dizziness in 600 mg P groupLaparoscopic hysterectomy, GAJokela and colleagues26Jokela R Ahonen J Tallgren M Haanpaa M Korttila K A randomized controlled trial of perioperative administration of pregabalin for pain after laparoscopic hysterectomy.Pain. 2008; 134: 106-112doi:10.1016/j.pain.2007.04.002Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar556 (two P treatment arms)/2875 and 1501 h preopP<0.05 in 150 mg groupI.V. fentanylNSNSNSDay-case gynaecological laparoscopic surgery, GAMathiesen and colleagues24Mathiesen O Jacobsen LS Holm HE et al.Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty.Br J Anaesth. 2008; 101: 535-541doi:10.1093/bja/aen215Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar782 (one of the treatment arm using dexamethasone)/383001 h preopNSI.V. PCA morphineP<0.05—More sedation in P groupTotal hip arthroplasty, RAMathiesen and colleagues25Mathiesen O Rasmussen ML Dierking G et al.Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial.Acta Anaesthesiol Scand. 2009; 53: 227-235doi:10.1111/j.1399-6576.2008.01821.xCrossref PubMed Scopus (101) Google Scholar676 (one of the treatment arm using dexamethasone)/403001 h preopNSI.V. PCA morphineNS—Less vomit in P groupAbdominal hysterectomy, GAChang and colleagues17Chang SH Lee HW Kim HK Kim SH Kim DK An evaluation of perioperative pregabalin for prevention and attenuation of postoperative shoulder pain after laparoscopic cholecystectomy.Anesth Analg. 2009; 109: 1284-1286doi:10.1213/ane.0b013e3181b4874dCrossref PubMed Scopus (77) Google Scholar339/383001 h preop and 12 h after first doseNSI.V. ketorolacNS—More sedation in P groupLaparoscopic cholecystectomy, GACabrera Schulmeyer and colleagues23Cabrera Schulmeyer MC de la Maza J Ovalle C Farias C Vives I Analgesic effects of a single preoperative dose of pregabalin after laparoscopic sleeve gastrectomy.Obes Surg. 2010; 20: 1678-1681Crossref PubMed Scopus (66) Google Scholar639/411502 h preopP<0.05I.V. morphineP<0.05—Less PONV in P groupLaparoscopic sleeve gastrectomy, GAIttichaikulthol and colleagues21Ittichaikulthol W Virankabutra T Kunopart M Khamhom W Putarawuthichai P Rungphet S Effects of pregabalin on post operative morphine consumption and pain after abdominal hysterectomy with/without salphingo-oophorectomy: a randomized, double-blind trial.J Med Assoc Thai. 2009; 92: 1318-1323PubMed Google Scholar338/403001 h preopP<0.01I.V. PCA morphineP<0.01—NSAbdominal hysterectomy, GAKim and colleagues22Kim SY Jeong JJ Chung WY Kim HJ Nam KH Shim YH Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: a randomized clinical trial.Surg Endosc. 2010; 24: 2776-2781Crossref PubMed Scopus (70) Google Scholar547/473001 h preop and 12 h after first doseP<0.05I.V. ketorolac and p.o. ibuprofen——More sedation and dizziness in P groupEndoscopic thyroidectomy, GA Open table in a new tab The types of surgery were of great heterogeneity. Most patients in the studies received general anaesthesia, except in two studies where spinal anaesthesia and local anaesthesia were administered.18Hill CM Balkenohl M Thomas DW Walker R Mathe H Murray G Pregabalin in patients with postoperative dental pain.Eur J Pain. 2001; 5: 119-124doi:10.1053/eujp.2001.0235Crossref PubMed Scopus (2) Google Scholar 24Mathiesen O Jacobsen LS Holm HE et al.Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty.Br J Anaesth. 2008; 101: 535-541doi:10.1093/bja/aen215Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar Pregabalin was administered as a single preoperative dose in seven studies,19Paech MJ Goy R Chua S Scott K Christmas T Doherty DA A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery.Anesth Analg. 2007; 105 (table of contents): 1449-1453doi:10.1213/01.ane.0000286227.13306.d7Crossref PubMed Scopus (108) Google Scholar, 20Jokela R Ahonen J Tallgren M Haanpaa M Korttila K Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery.Br J Anaesth. 2008; 100: 834-840doi:10.1093/bja/aen098Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar, 21Ittichaikulthol W Virankabutra T Kunopart M Khamhom W Putarawuthichai P Rungphet S Effects of pregabalin on post operative morphine consumption and pain after abdominal hysterectomy with/without salphingo-oophorectomy: a randomized, double-blind trial.J Med Assoc Thai. 2009; 92: 1318-1323PubMed Google Scholar 23Cabrera Schulmeyer MC de la Maza J Ovalle C Farias C Vives I Analgesic effects of a single preoperative dose of pregabalin after laparoscopic sleeve gastrectomy.Obes Surg. 2010; 20: 1678-1681Crossref PubMed Scopus (66) Google Scholar, 24Mathiesen O Jacobsen LS Holm HE et al.Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty.Br J Anaesth. 2008; 101: 535-541doi:10.1093/bja/aen215Abstract Full Text Full Text PDF PubMed Scopus (164) Google Scholar, 25Mathiesen O Rasmussen ML Dierking G et al.Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial.Acta Anaesthesiol Scand. 2009; 53: 227-235doi:10.1111/j.1399-6576.2008.01821.xCrossref PubMed Scopus (101) Google Scholar 27Agarwal A Gautam S Gupta D Agarwal S Singh PK Singh U Evaluation of a single preoperative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy.Br J Anaesth. 2008; 101: 700-704doi:10.1093/bja/aen244Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar as a single postoperative dose in one study,18Hill CM Balkenohl M Thomas DW Walker R Mathe H Murray G Pregabalin in patients with postoperative dental pain.Eur J Pain. 2001; 5: 119-124doi:10.1053/eujp.2001.0235Crossref PubMed Scopus (2) Google Scholar and as two separate preoperative and postoperative doses in three studies.17Chang SH Lee HW Kim HK Kim SH Kim DK An evaluation of perioperative pregabalin for prevention and attenuation of postoperative shoulder pain after laparoscopic cholecystectomy.Anesth Analg. 2009; 109: 1284-1286doi:10.1213/ane.0b013e3181b4874dCrossref PubMed Scopus (77) Google Scholar 22Kim SY Jeong JJ Chung WY Kim HJ Nam KH Shim YH Perioperative administration of pregabalin for pain after robot-assisted endoscopic thyroidectomy: a randomized clinical trial.Surg Endosc. 2010; 24: 2776-2781Crossref PubMed Scopus (70) Google Scholar 26Jokela R Ahonen J Tallgren M Haanpaa M Korttila K A randomized controlled trial of perioperative administration of pregabalin for pain after laparoscopic hysterectomy.Pain. 2008; 134: 106-112doi:10.1016/j.pain.2007.04.002Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar The dose of pregabalin ranged from 50 to 600 mg. To facilitate quantitative analysis, a dose of 300 mg day−1 was used as a cut-off to divide the treatment groups into two groups: (i) group receiving <300 mg of pregabalin per day and (ii) group receiving ≥300 mg of pregabalin per day. Pain intensity and 24 h postoperative analgesic consumption were analysed separately in each group (Fig. 2). Data on adverse effects were pooled and analysed together because of the small number of clinical trials in each subgroup. Five trials with six treatment arms used a perioperative pregabalin dose of <300 mg day−1. Pregabalin was administered before operation as one dose in four of these trials,19Paech MJ Goy R Chua S Scott K Christmas T Doherty DA A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery.Anesth Analg. 2007; 105 (table of contents): 1449-1453doi:10.1213/01.ane.0000286227.13306.d7Crossref PubMed Scopus (108) Google Scholar 20Jokela R Ahonen J Tallgren M Haanpaa M Korttila K Premedication with pregabalin 75 or 150 mg with ibuprofen to control pain after day-case gynaecological laparoscopic surgery.Br J Anaesth. 2008; 100: 834-840doi:10.1093/bja/aen098Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar 23Cabrera Schulmeyer MC de la Maza J Ovalle C Farias C Vives I Analgesic effects of a single preoperative dose of pregabalin after laparoscopic sleeve gastrectomy.Obes Surg. 2010; 20: 1678-1681Crossref PubMed Scopus (66) Google Scholar 27Agarwal A Gautam S Gupta D Agarwal S Singh PK Singh U Evaluation of a single preoperative dose of pregabalin for attenuation of postoperative pain after laparoscopic cholecystectomy.Br J Anaesth. 2008; 101: 700-704doi:10.1093/bja/aen244Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar whereas the remaining trial used pregabalin after operation.18Hill CM Balkenohl M Thomas DW Walker R Mathe H Murray G Pregabalin in patients with postoperative dental pain.Eur J Pain. 2001; 5: 119-124doi:10.1053/eujp.2001.0235Crossref PubMed Scopus (2) Google Scholar One study did not report pain intensity with VAS scores.18Hill CM Balkenohl M Thomas DW Walker R Mathe H Murray G Pregabalin in patients with postoperative dental pain.Eur J Pain. 2001; 5: 119-124doi:10.1053/eujp.2001.0235Crossref PubMed Scopus (2) Google Scholar Postoperative pain intensity was presented as median or median with inter-quartile ranges or percentile ranges in the other four studies and was not suitable for meta-analysis.19Paech MJ Goy R Chua S Scott K Christmas T Doherty DA A randomized, placebo-controlled trial of preoperative oral pregabalin for postoperative pain relief after minor gynecological surgery.Anesth Analg. 2007; 105 (table of contents): 1449-1453doi:10.1213/01.ane.0000286227.13306.d7Crossref PubMed Scopus (108) Google Scholar 20Jokela R Ahonen J Tallgren M Haanpaa M Korttila K Premedication with pregabalin 75 or 150 mg with ibuprofen to contr