title: Perioperative use of pregabalin for acute pain-a systematic review and meta-analysis.
abstract: Evidence supporting postoperative pain management using pregabalin as an adjunct intervention across various surgical pain models is lacking. The objective of this systematic review was to evaluate "model-specific" comparative effectiveness and harms of pregabalin following a previously published systematic review protocol. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched from inception through August 2013. Data were screened and single extraction with independent verification and dual risk of bias assessment was performed. Quality of evidence (QoE) was rated using the GRADE approach. Primary outcomes were pain relief at rest and on movement and reduction in postoperative analgesic consumption. A total of 1423 records were screened, and 43 studies were included. Perioperative pregabalin resulted in: 16% (95% confidence interval [CI], 9%-21%) reduction in analgesic consumption (moderate QoE, 24 trials) and a small reduction in the magnitude of pain in surgeries associated with pronociceptive pain. Per 1000 patients, 10 more will experience blurred vision (95% CI, 5-20 more; moderate QoE, 17 trials) and 41 more sedation (95% CI, 13-77 more, 17 trials). To prevent 1 case of perioperative nausea and vomiting, the number needed to treat is 11 (95% CI: 7-28, 25 trials). Inadequate evidence addressed outcomes of enhanced recovery and serious harms. Pregabalin analgesic effectiveness is largely restricted to surgical procedures associated with pronociceptive mechanisms. The clinical significance of observed pregabalin benefits must be weighed against the uncertainties about serious harms and enhanced recovery to inform the careful selection of surgical patients. Recommendations for future research are proposed.
authors.affiliation: Department of Anesthesiology, The Ottawa Hospital, Ottawa, ON, Canada Knowledge Synthesis Group, Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Naveen
authors.initials: N
authors.lastname: Eipe
authors.forename: John
authors.initials: J
authors.lastname: Penning
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Yazdi
authors.forename: Ranjeeta
authors.initials: R
authors.lastname: Mallick
authors.forename: Lucy
authors.initials: L
authors.lastname: Turner
authors.forename: Nadera
authors.initials: N
authors.lastname: Ahmadzai
authors.forename: Mohammed Toseef
authors.initials: MT
authors.lastname: Ansari
mesh_terms: D059787:Acute Pain / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D000700:Analgesics / Q000008:administration & dosage*; D006801:Humans; D059408:Pain Management / Q000379:methods; D010149:Postoperative Pain / Q000175:diagnosis / Q000453:epidemiology / Q000517:prevention & control*; D000069583:Pregabalin / Q000008:administration & dosage*; D011300:Preoperative Care / Q000379:methods*; D016032:Randomized Controlled Trials as Topic / Q000379:methods
chemical_list: D000700:Analgesics; D000069583:Pregabalin
references.citation: Agarwal 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;101:700–4.
references.citation: Balaban F, Yagar S, Ozgok A, Koc M, Gullapoglu H. A randomized, placebo-controlled study of pregabalin for postoperative pain intensity after laparoscopic cholecystectomy. J Clin Anesth 2012;24:175–8.
references.citation: Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, Vist GE, Falck-Ytter Y, Meerpohl J, Norris S, Guyatt GH. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol 2011;64:401–6.
references.citation: Bornemann-Cimenti H, Lederer AJ, Wejbora M, Michaeli K, Kern-Pirsch C, Archan S, Rumpold-Seitlinger G, Zigeuner R, Sandner-Kiesling A. Preoperative pregabalin administration significantly reduces postoperative opioid consumption and mechanical hyperalgesia after transperitoneal nephrectomy. Br J Anaesth 2012;108:845–9.
references.citation: Burke SM, Shorten GD. Perioperative pregabalin improves pain and functional outcomes 3 months after lumbar discectomy. Anesth Analg 2010;110:1180–5.
references.citation: Buvanendran 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;110:199–207.
references.citation: Buvanendran A, Kroin JS, Della Valle CJ, Moric M, Tuman KJ. Cerebrospinal fluid neurotransmitter changes during the perioperative period in patients undergoing total knee replacement: a randomized trial. Anesth Analg 2012;114:434–41.
references.citation: Cabrera 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;20:1678–81.
references.citation: Carmichael NM, Katz J, Clarke H, Kennedy D, Kreder HJ, Gollish J, McCartney CJ. An intensive perioperative regimen of pregabalin and celecoxib reduces pain and improves physical function scores six weeks after total hip arthroplasty: a prospective randomized controlled trial. Pain Res Manag 2013;18:127–32.
references.citation: Chang 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;109:1284–6.
references.citation: Chaparro LE, Clarke H, Valdes PA, Mira M, Duque L, Mitsakakis N. Adding pregabalin to a multimodal analgesic regimen does not reduce pain scores following cosmetic surgery: a randomized trial. J Anesth 2012;26:829–35.
references.citation: Choi YS, Shim JK, Song JW, Kim JC, Yoo YC, Kwak YL. Combination of pregabalin and dexamethasone for postoperative pain and functional outcome in patients undergoing lumbar spinal surgery: a randomized placebo-controlled trial. Clin J Pain 2013;29:9–14.
references.citation: Clendenen S, Rajendran S, Kopacz D, Greengrass R, Robards C, Weinstein D. Pregabalin as an adjunct to a multimodal analgesic regimen to achieve opioid sparing in arthroscopic rotator cuff repair. Rom J Anaesth Intens Care 2010;17:5–10.
references.citation: Dauri 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;10:716–33.
references.citation: DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–88.
references.citation: Eipe N, Penning J. Postoperative respiratory depression with pregabalin: a case series and a preoperative decision algorithm. Pain Res Manag 2011;16:353–6.
references.citation: Eipe N, Penning J, Ansari M, Yazdi F, Ahmadzai N. A protocol for a systematic review for perioperative pregabalin use. Syst Rev 2012;1:40.
references.citation: Engelman E, Cateloy F. Efficacy and safety of perioperative pregabalin for post-operative pain: a meta-analysis of randomized-controlled trials. Acta Anaesthesiol Scand 2011;55:927–43.
references.citation: Fassoulaki A, Melemeni A, Tsaroucha A, Paraskeva A. Perioperative pregabalin for acute and chronic pain after abdominal hysterectomy or myomectomy: a randomised controlled trial. Eur J Anaesthesiol 2012;29:531–6.
references.citation: Freedman BM, O'Hara E. Pregabalin has opioid-sparing effects following augmentation mammaplasty. Aesthet Surg J 2008;28:421–4.
references.citation: Friedrich JO, Adhikari NK, Beyene J. The ratio of means method as an alternative to mean differences for analyzing continuous outcome variables in meta-analysis: a simulation study. BMC Med Res Methodol 2008;8:32.
references.citation: Friedrich JO, Adhikari NK, Beyene J. Ratio of means for analyzing continuous outcomes in meta-analysis performed as well as mean difference methods. J Clin Epidemiol 2011;64:556–64.
references.citation: Gajraj NM. Pregabalin: its pharmacology and use in pain management. Anesth Analg 2007;105:1805–15.
references.citation: Ghai A, Gupta M, Hooda S, Singla D, Wadhera R. A randomized controlled trial to compare pregabalin with gabapentin for postoperative pain in abdominal hysterectomy. Saudi J Anaesth 2011;5:252–7.
references.citation: Gianesello L, Pavoni V, Barboni E, Galeotti I, Nella A. Perioperative pregabalin for postoperative pain control and quality of life after major spinal surgery. J Neurosurg Anesthesiol 2012;24:121–6.
references.citation: Hegarty DA, Shorten GD. A Randomised, placebo-controlled trial of the effects of preoperative pregabalin on pain intensity and opioid consumption following lumbar discectomy. Korean J Pain 2011;24:22–30.
references.citation: Hill CM, Balkenohl M, Thomas DW, Walker R, Mathe H, Murray G. Pregabalin in patients with postoperative dental pain. Eur J Pain 2001;5:119–24.
references.citation: Ittichaikulthol 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;92:1318–23.
references.citation: Jain P, Jolly A, Bholla V, Adatia S, Sood J. Evaluation of efficacy of oral pregabalin in reducing postoperative pain in patients undergoing total knee arthroplasty. Indian J Orthop 2012;46:646–52.
references.citation: Jokela 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;134:106–12.
references.citation: Jokela 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;100:834–40.
references.citation: Joshi SS, Jagadeesh AM. Efficacy of perioperative pregabalin in acute and chronic post-operative pain after off-pump coronary artery bypass surgery: a randomized, double-blind placebo controlled trial. Ann Card Anaesth 2013;16:180–5.
references.citation: Kim JC, Choi YS, Kim KN, Shim JK, Lee JY, Kwak YL. Effective dose of peri-operative oral pregabalin as an adjunct to multimodal analgesic regimen in lumbar spinal fusion surgery. Spine (Phila Pa 1976) 2011;36:428–33.
references.citation: Kim 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;24:2776–81.
references.citation: Kim SY, Song JW, Park B, Park S, An YJ, Shim YH. Pregabalin reduces post-operative pain after mastectomy: a double-blind, randomized, placebo-controlled study. Acta Anaesthesiol Scand 2011;55:290–6.
references.citation: Kohli M, Murali T, Gupta R, Khan P, Bogra J. Optimization of subarachanoid block by oral pregabalin for hysterectomy. J Anaesthesiol Clin Pharmacol 2011;27:101–5.
references.citation: Kumar KP, Kulkarni DK, Gurajala I, Gopinath R. Pregabalin versus tramadol for postoperative pain management in patients undergoing lumbar laminectomy: a randomized, double-blinded, placebo-controlled study. J Pain Res 2013;6:471–8.
references.citation: Lee C, Lee HW, Kim JN. Effect of oral pregabalin on opioid-induced hyperalgesia in patients undergoing laparo-endoscopic single-site urologic surgery. Korean J Anesthesiol 2013;64:19–24.
references.citation: Mathiesen O, Jacobsen LS, Holm HE, Randall S, Adamiec-Malmstroem L, Graungaard BK, Holst PE, Hilsted KL, Dahl JB. Pregabalin and dexamethasone for postoperative pain control: a randomized controlled study in hip arthroplasty. Br J Anaesth 2008;101:535–41.
references.citation: Mathiesen O, Jorgensen DG, Hilsted KL, Trolle W, Stjernholm P, Christiansen H, Hjortso NC, Dahl JB. Pregabalin and dexamethasone improves post-operative pain treatment after tonsillectomy. Acta Anaesthesiol Scand 2011;55:297–305.
references.citation: Mathiesen O, Rasmussen ML, Dierking G, Lech K, Hilsted KL, Fomsgaard JS, Lose G, Dahl JB. Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial. Acta Anaesthesiol Scand 2009;53:227–35.
references.citation: Nimmaanrat S, Tangtrakulwanish B, Klabklay P, Boonriong T. Perioperative administration of pregabalin in patients undergoing arthroscopic anterior cruciate ligament reconstruction: does it help to relieve postoperative pain? J Med Assoc Thai 2012;95:1297–301.
references.citation: Ozgencil E, Yalcin S, Tuna H, Yorukoglu D, Kecik Y. Perioperative administration of gabapentin 1,200 mg day-1 and pregabalin 300 mg day-1 for pain following lumbar laminectomy and discectomy: a randomised, double-blinded, placebo-controlled study. Singapore Med J 2011;52:883–9.
references.citation: Paech 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;105:1449–53.
references.citation: Pakravan M, Roshani M, Yazdani S, Faramazi A, Yaseri M. Pregabalin and gabapentin for post-photorefractive keratectomy pain: a randomized controlled trial. Eur J Ophthalmol 2012;22(suppl 7):S106–13.
references.citation: Peng PW, Li C, Farcas E, Haley A, Wong W, Bender J, Chung F. Use of low-dose pregabalin in patients undergoing laparoscopic cholecystectomy. Br J Anaesth 2010;105:155–61.
references.citation: Pesonen A, Suojaranta-Ylinen R, Hammaren E, Kontinen VK, Raivio P, Tarkkila P, Rosenberg PH. Pregabalin has an opioid-sparing effect in elderly patients after cardiac surgery: a randomized placebo-controlled trial. Br J Anaesth 2011;106:873–81.
references.citation: Przesmycki K, Wiater-Koziol E, Kotarski J, Czuczwar M, Jaskowiak R, Zabek M, Kolacz A, Fijalkowska M, Kotus M. Effect of pre-emptive pregabalin on pain intensity and morphine requirement after hysterectomy [in Polish]. Anestezjol Intens Ter 2011;43:14–17.
references.citation: Sarakatsianou C, Theodorou E, Georgopoulou S, Stamatiou G, Tzovaras G. Effect of pre-emptive pregabalin on pain intensity and postoperative morphine consumption after laparoscopic cholecystectomy. Surg Endosc 2013;27:2504–11.
references.citation: Spreng UJ, Dahl V, Raeder J. Effect of a single dose of pregabalin on post-operative pain and pre-operative anxiety in patients undergoing discectomy. Acta Anaesthesiol Scand 2011;55:571–6.
references.citation: Toth C. Pregabalin: latest safety evidence and clinical implications for the management of neuropathic pain. Ther Adv Drug Saf 2014;5:38–56.
references.citation: Wang H, Gargano C, Lukac S, Jackson A, Beals C, Smiley P, Drexel M, Ruddy M, Herman G, Johnson-Levonas AO, Medve R, Webster L, Reicin A. An enhanced bunionectomy model as a potential tool for early decision-making in the development of new analgesics. Adv Ther 2010;27:963–80.
references.citation: Wensel TM, Powe KW, Cates ME. Pregabalin for the treatment of generalized anxiety disorder. Ann Pharmacother 2012;46:424–9.
references.citation: Yadeau JT, Paroli L, Kahn RL, Jules-Elysee KM, Lasala VR, Liu SS, Lin E, Powell K, Buschiazzo VL, Wukovits B, Roberts MM, Levine DS. Addition of pregabalin to multimodal analgesic therapy following ankle surgery: a randomized double-blind, placebo-controlled trial. Reg Anesth Pain Med 2012;37:302–7.
references.citation: Yu L, Ran B, Li M, Shi Z. Gabapentin and pregabalin in the management of postoperative pain after lumbar spinal surgery: a systematic review and meta-analysis. Spine (Phila Pa 1976) 2013;38:1947–52.
references.citation: Zhang J, Ho KY, Wang Y. Efficacy of pregabalin in acute postoperative pain: a meta-analysis. Br J Anaesth 2011;106:454–62.