title: The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis.
abstract: Whether preemptive analgesic interventions are more effective than conventional regimens in managing acute postoperative pain remains controversial. We systematically searched for randomized controlled trials that specifically compared preoperative analgesic interventions with similar postoperative analgesic interventions via the same route. The retrieved reports were stratified according to five types of analgesic interventions: epidural analgesia, local anesthetic wound infiltration, systemic N-methyl-d-aspartic acid (NMDA) receptor antagonists, systemic nonsteroidal antiinflammatory drugs (NSAIDs), and systemic opioids. The primary outcome measures analyzed were the pain intensity scores, supplemental analgesic consumption, and time to first analgesic consumption. Sixty-six studies with data from 3261 patients were analyzed. Data were combined by using a fixed-effect model, and the effect size index (ES) used was the standardized mean difference. When the data from all three outcome measures were combined, the ES was most pronounced for preemptive administration of epidural analgesia (ES, 0.38; 95% confidence interval [CI], 0.28-0.47), local anesthetic wound infiltration (ES, 0.29; 95% CI, 0.17-0.40), and NSAID administration (ES, 0.39; 95% CI, 0.27-0.48). Whereas preemptive epidural analgesia resulted in consistent improvements in all three outcome variables, preemptive local anesthetic wound infiltration and NSAID administration improved analgesic consumption and time to first rescue analgesic request, but not postoperative pain scores. The least proof of efficacy was found in the case of systemic NMDA antagonist (ES, 0.09; 95% CI, -0.03 to 0.22) and opioid (ES, -0.10; 95% CI, -0.26 to 0.07) administration, and the results remain equivocal.
authors.affiliation: *Department of Oral & Maxillofacial Surgery, Faculty of Dentistry, National University of Singapore; †Department of Anesthesiology & Critical Care Medicine, Faculty of Medicine, Medical University of Innsbruck, Innsbruck, Austria; ‡Department of Restorative Dentistry, Faculty of Dentistry, University of Newcastle upon Tyne, Newcastle upon Tyne, United Kingdom; and §Department of Anaesthetics and Intensive Care Medicine, College of Medicine, University of Wales, United Kingdom.
authors.forename: Cliff K-S
authors.initials: CK
authors.lastname: Ong
authors.forename: Philipp
authors.initials: P
authors.lastname: Lirk
authors.forename: Robin A
authors.initials: RA
authors.lastname: Seymour
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Jenkins
mesh_terms: D000208:Acute Disease; D015360:Analgesia, Epidural; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D006801:Humans; D010147:Pain Measurement; D010149:Postoperative Pain / Q000188:drug therapy*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016194:Receptors, N-Methyl-D-Aspartate
references.citation: Woolf CJ, Wall PD. Morphine-sensitive and morphine-insensitive actions of C-fiber input on the rat spinal cord. Neurosci Lett 1986;64:221–5.
references.citation: Kissin I. Preemptive analgesia. Anesthesiology 2000;93:1138–43.
references.citation: Wilder-Smith OH. Pre-emptive analgesia and surgical pain. Prog Brain Res 2000;129:505–24.
references.citation: Kelly DJ, Ahmad M, Brull SJ. Preemptive analgesia. II. Recent advances and current trends. Can J Anaesth 2001;48:1091–101.
references.citation: McQuay HJ. Do pre-emptive treatments provide better pain control? In: Gebhart GF, Hammond DL, Jesen TS, eds. Proceedings of the 7th World Congress on Pain: progress in pain research and management. Vol 2. Seattle: IASP Press, 1994:709–23.
references.citation: Niv D, Lang E, Devor M. The effect of preemptive analgesia on acute postoperative pain. Minerva Anestesiol 1999;65:127–40.
references.citation: Moiniche S, Kehlet H, Dahl JB. A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief. Anesthesiology 2002;96:725–41.
references.citation: Kissin I. Preemptive analgesia: why its effect is not always obvious. Anesthesiology 1996;84:1015–9.
references.citation: Katz J, McCartney CJL. Current status of preemptive analgesia. Curr Opin Anaesthesiol 2002;15:435–41.
references.citation: Dahl JB, Kehlet H. The value of pre-emptive analgesia in the treatment of postoperative pain. Br J Anaesth 1993;70:434–9.
references.citation: Woolf CJ, Chong MS. Pre-emptive analgesia: treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993;77:362–79.
references.citation: Penning JP. Pre-emptive analgesia: what does it mean to the clinical anaesthetist? Can J Anaesth 1996;43:97–101.
references.citation: Ong KS, Seymour RA. An evidence-based medicine approach to pre-emptive analgesia. Am J Pain Manage 2003;13:150–64.
references.citation: Wall PD. The prevention of postoperative pain. Pain 1988;33:289–90.
references.citation: Mulrow CD, Oxman A, eds. How to conduct a Conchrane systematic review. The Cochrane Library (Issue 2). The Cochrane Collaboration Handbook (version 3.0.2). San Antonio Cochrane Collaboration, 1997.
references.citation: Jadad A, Moore A, Carrol D, et al. Assessing the quality of randomized trials: is blinding necessary? Control Clin Trials 1996;17:1–12.
references.citation: L’Abbe KA, Detsky AS, O’Rourke K. Meta-analysis in clinical research. Ann Intern Med 1987;107:224–33.
references.citation: Hedges LV, Olkin I. Vote-counting methods in research synthesis. Psychol Bull 1980;88:359–69.
references.citation: Lewis S, Clarke M. Forrest plots: trying to see the wood and trees. BMJ 2001;322:1479–80.
references.citation: Sterne JA, Gavaghan D, Egger M. Publication and related bias in meta-analysis: power of statistical tests and prevalence in the literature. J Clin Epidemiol 2000;53:1119–29.
references.citation: Beilin B, Bessler H, Mayburd E, et al. Effects of preemptive analgesia on pain and cytokine production in the postoperative period. Anesthesiology 2003;98:151–5.
references.citation: Burmeister MA, Gottschalk A, Freitag M, et al. Pre- and intra-operative epidural ropivacaine has no early preemptive analgesic effect in major gynecologic surgery. Can J Anaesth 2003;50:568–73.
references.citation: Neustein SM, Kreitzer JM, Krellenstein D. Preemptive epidural analgesia for thoracic surgery. Mt Sinai J Med 2002;69:101–4.
references.citation: Flisberg P, Tornebrandt K, Walther B, Lundberg J. A comparison of the effects on postoperative pain relief of epidural analgesia started before or after surgery. Eur J Anaesthesiol 2000;17:627–33.
references.citation: Kirdemir P, Ozkocak I, Demir T, Gogus N. Comparison of postoperative analgesic effects of preemptively used epidural ketamine and neostigmine. J Clin Anesth 2000;12:543–8.
references.citation: Vaida SJ, David BB, Somri M, et al. The influence of preemptive spinal anesthesia on postoperative pain. Clin Anesth 2000;12:374–7.
references.citation: Wu CT, Yeh CC, Yu JC, et al. Pre-incisional epidural ketamine, morphine and bupivacaine combined with epidural and general anaesthesia provides pre-emptive analgesia for upper abdominal surgery. Acta Anaesthesiol Scand 2000;44:63–8.
references.citation: Gottschalk A, Smith DS, Jobes DR, et al. Preemptive epidural analgesia and recovery from radical prostatectomy. JAMA 1998;279:1076–82.
references.citation: Kucuk N, Kizilkaya M, Tokdemir M, et al. Preoperative epidural ketamine does not have a postoperative opioid sparing effect. Anesth Analg 1998;87:103–6.
references.citation: Rockemann MG, Seeling W, Pressler S, et al. Reduced postoperative analgesic demand after inhaled anesthesia in comparison to combined epidural-inhaled anesthesia in patients undergoing abdominal surgery. Anesth Analg 1997;84:600–5.
references.citation: Williams-Russo P, Sharrock NE, Haas SB, et al. Randomized trial of epidural versus general anesthesia: outcomes after primary total knee replacement. Clin Orthop 1996;331:199–208.
references.citation: Moiniche S, Hjortso NC, Hansen BL, et al. The effect of balanced analgesia on early convalescence after major orthopaedic surgery. Acta Anaesthesiol Scand 1994;38:328–35.
references.citation: Cerfolio RJ, Brant AS, Bass CS, Martolucci AA. A prospective double-blinded randomized trial evaluating the use of preemptive analgesia of the skin before thoracotomy. Ann Thorac Surg 2003;76:1055–8.
references.citation: Maestroni U, Sortini D, Devito C, et al. A new method of preemptive analgesia in laparoscopic cholecystectomy. Surg Endosc 2002;16:1336–40.
references.citation: Gatt CJ, Parker RD, Tetzlaff JE, et al. Preemptive analgesia: its role and efficacy in anterior cruciate ligament reconstruction. Am J Sports Med 1998;26:524–9.
references.citation: Campbell WI, Kendrick RW, Fee JPH. Balanced pre-emptive analgesia: does it work? A double-blind, controlled study in bilaterally symmetrical oral surgery. Br J Anaesth 1998;81:727–30.
references.citation: Hoard MA, Bill TJ, Campbell RL. Reduction in morbidity after iliac crest bone harvesting: the concept of preemptive analgesia. J Craniofac Surg 1998;9:448–51.
references.citation: Ke RW, Portera SG, Lincoln SR. A randomized blinded trial of preemptive local anesthesia in laparoscopy. Prim Care Update Ob Gyns 1998;5:197–8.
references.citation: Ko CY, Thompson JE, Alcantara A, Hiyama D. Preemptive analgesia in patients undergoing appendectomy. Arch Surg 1997;132:874–7.
references.citation: Campbell WI, Kendrick RW. Pre-emptive analgesia using local anaesthesia: a study in bilaterally symmetrical oral surgery. Br J Anaesth 1997;79:657–9.
references.citation: Pedersen JL, Crawford ME, Dahl JB, et al. Effect of preemptive nerve block on inflammation and hyperalgesia after human thermal injury. Anesthesiology 1996;84:1020–6.
references.citation: Elhakim M, Abdel HH. Comparison of preoperative with postoperative topical lidocaine spray on pain after tonsillectomy. Acta Anaesthesiol Scand 1995;39:1032–5.
references.citation: Wu CT, Yu JC, Liu ST, et al. Preincisional dextromethorphan treatment for postoperative pain management after upper abdominal surgery. World J Surg 2000;24:512–7.
references.citation: Fu ES, Miguel R, Scharf JE, et al. Preemptive ketamine decreases postoperative narcotic requirements in patients undergoing abdominal surgery. Anesth Analg 1997;34:1086–90.
references.citation: Tverskoy M, Oz Y, Isakson A, et al. Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesth Analg 1994;78:205–9.
references.citation: Oztekin S, Hepaguslar H, Kar AA, et al. Preemptive diclofenac reduces morphine use after remifentanil-based anaesthesia for tonsillectomy. Paediatr Anaesth 2002;12:694–9.
references.citation: Hanlon DM, Thambipillai T, Colbert ST, et al. Regional anesthesia and pain: timing of pre-emptive tenoxicam is important for postoperative analgesia. Can J Anaesth 2001;48:162–6.
references.citation: Mixter CG, Hacket TR. Preemptive analgesia in the laparoscopic patient. Surg Endosc 1997;11:351–3.
references.citation: Espinet A, Henderson DJ, Faccenda KA, et al. Does pre-incisional thoracic extradural block combined with diclofenac reduce postoperative pain after abdominal hysterectomy? Br J Anaesth 1996;76:209–13.
references.citation: Romej M, Vopel-Lewis T, Merkel SI, Reyneolds PI. Effect of preemptive acetaminophen on postoperative pain scores and oral fluid intake in pediatric tonsillectomy patients. AANA J 1996;64:535–40.
references.citation: Sandin R, Sternlo JE, Stam H, et al. Diclofenac for pain relief after arthroscopy: a comparison of early and delayed treatment. Acta Anaesthesiol Scand 1993;37:747–50.
references.citation: Vogel RI, Desjardins PJ, Major KVO. Comparison of presurgical and immediate postsurgical ibuprofen on postoperative periodontal pain. J Periodontol 1992;63:914–8.
references.citation: Flath RK, Hicks ML, Dionne RA, et al. Pain suppression after pulpectomy with preoperative flurbiprofen. J Endod 1987;13:339–46.
references.citation: Chiaretti A, Viola L, Pietrini D, et al. Preemptive analgesia with tramadol and fentanyl in pediatric neurosurgery. Childs Nerv Syst 2000;16:93–9.
references.citation: Motamed C, Mazoit X, Ghanouchi K, et al. Preemptive intravenous morphine-6-glucuronide is ineffective for postoperative pain relief. Anesthesiology 2000;92:355–60.
references.citation: Collis R, Brandner B, Bromley LM, et al. Is there any clinical advantage of increasing the pre-emptive dose of morphine or combining pre-incisional with postoperative morphine administration? Br J Anaesth 1995;74:396–9.
references.citation: Katz J, Cohen L, Schmid R, et al. Postoperative morphine use and hyperalgesia are reduced by preoperative but not postoperative epidural analgesia: implications for preemptive analgesia and the prevention of central sensitization. Anesthesiology 2003;98:1449–60.
references.citation: Esmaoglu A, Cuha Y, Boyaci A. Preemptive efficacy of epidural fentanyl in elective abdominal surgery. Eur J Anaesthesiol 2001;18:59–63.
references.citation: Aida S, Fujihara H, Taga K, et al. Involvement of presurgical pain in preemptive analgesia for orthopedic surgery. Pain 2000;84:169–73.
references.citation: Subramaniam B, Pawar DK, Kashyap L. Preemptive analgesia with epidural morphine or morphine with bupivacaine. Anaesth Intensive Care 2000;28:392–8.
references.citation: Aida S, Baba H, Yamakura T, et al. The effectiveness of preemptive analgesia varies according to the type of surgery. Anesth Analg 1999;89:771–6.
references.citation: Obata H, Saito S, Fujita N, et al. Epidural block with mepivacaine before surgery reduces long-term post-thoracotomy pain. Can J Anaesth 1999;46:1127–32.
references.citation: Kundra P, Deepalakshmi K, Ravishankar M. Preemptive caudal bupivacaine and morphine for postoperative analgesia in children. Anesth Analg 1998;87:52–6.
references.citation: Richards JT, Read JRM, Chambers WA. Epidural anaesthesia as a method of preemptive analgesia for abdominal hysterectomy. Anaesthesia 1998;53:296–307.
references.citation: Wong CS, Lu CC, Cheng CH, Ho ST. Preemptive analgesia with ketamine, morphine and epidural lidocaine prior to total knee replacement. Can J Anaesth 1997;44:31–7.
references.citation: Choe H, Choi YS, Kim YH, Ko SH. Epidural morphine plus ketamine for upper abdominal surgery: improved analgesia from preincisional versus postincisional administration. Anesth Analg 1997;84:560–3.
references.citation: Kundra P, Gurnani A, Bhattacharya A. Preemptive epidural morphine for postoperative pain relief after lumbar laminectomy. Anesth Analg 1997;85:135–8.
references.citation: Aguilar J, Domingo V, Espachs P, et al. Absence of an early preemptive effect after thoracic extradural bupivacaine in thoracic surgery. Br J Anaesth 1996;76:72–6.
references.citation: Dhal JB, Daugaard JJ, Rasmussen B. Immediate and prolonged effects of pre- versus postoperative epidural analgesia with bupivacaine and morphine on pain at rest and during mobilization after total knee arthroplasty. Acta Anaesthesiol Scand 1994;38:557–61.
references.citation: Holthusen H, Eichwede F, Stevens M, et al. Preemptive analgesia: comparison of preoperative with postoperative block on postoperative pain in children. Br J Anaesth 1994;73:440–2.
references.citation: Rockemann MG, Seeling W, Bischof C, et al. Prophylactic use of epidural mepivacaine. Anesthesiology 1996;84:1027–34.
references.citation: Katz J, Clairoux M, Kavanagh BP, et al. Preemptive lumbar epidural anaesthesia reduces postoperative pain and patient-controlled morphine consumption after lower abdominal surgery. Pain 1994;59:395–403.
references.citation: Pryle BJ, Vanner RG, Enriquez N, Renolds F. Can preemptive lumbar epidural blockade reduce postoperative pain following lower abdominal surgery? Anaesthesia 1993;48:120–3.
references.citation: Dahl JB, Hansen BL, Hjortso NC, et al. Influence of timing on the effect of continuous extradural analgesia with bupivacaine and morphine after major abdominal surgery. Br J Anaesth 1992;69:4–8.
references.citation: Rice LJ, Pudimat MA, Hannallah RS. Timing of caudal block placement in relation to surgery does not affect duration of postoperative analgesia in pediatric ambulatory patients. Can J Anaesth 1990;37:429–31.
references.citation: Mahfouz AK, Nabawi KS. Preemptive analgesia in rhegmatogenous retina detachment surgery: is it effective? Retina 2002;22:602–6.
references.citation: Reuben SS, Sklar J, El-Mansouri M. The preemptive analgesic effect of intraarticular bupivacaine and morphine after ambulatory arthroscopic knee surgery. Anesth Analg 2001;92:923–6.
references.citation: Kristin N, Schonfeld CL, Bechmann M, et al. Vitreoretinal surgery: preemptive analgesia. Br J Ophthalmol 2001;85:1328–31.
references.citation: Gill P, Kiani S, Victoria BA, et al. Preemptive analgesia with local anesthetic for herniorrhaphy. Anaesthesia 2001;56:414–7.
references.citation: Altintas F, Bozkurt P, Ipek N, Kaya G. The efficacy of pre- versus postsurgical axillary block on postoperative pain in paediatric patients. Paediatr Anaesth 2000;10:23–8.
references.citation: Hanlon DM, Colbert ST, Keane PW, et al. Preemptive bupivacaine offers no advantages to postoperative wound infiltration in analgesia for outpatient breast biopsy. Am J Surg 2000;180:29–32.
references.citation: Fischer S, Troidl H, Maclean AA, et al. Prospective double-blind randomized study of a new regime of preemptive analgesia for inguinal hernia repair. Eur J Surg 2000;166:545–51.
references.citation: Ke RW, Porte SG, Bagous W, Lincoln SR. A randomized blinded trial of preemptive analgesia in laparoscopy. Obstet Gynecol 1998;92:972–5.
references.citation: Molliex S, Haond P, Baylot D. Effect of pre- versus postoperative tonsillar infiltration with local anesthetics on postoperative pain after tonsillectomy. Acta Anaesthesiol Scand 1996;40:1210–5.
references.citation: Pasqualucci A, Angelis VD, Contardo R, et al. Preemptive analgesia: intraperitoneal local anesthetic in laparoscopic cholecystectomy. Anesthesiology 1996;85:11–20.
references.citation: Dahl V, Raeder JC, Erno PE, et al. Preemptive effect of preincisional versus postincisional infiltration of local anaesthetic on children undergoing hernioplasty. Acta Anaesthesiol Scand 1996;40:847–51.
references.citation: Huffnagle HJ, Norris MC, Barbara LL, et al. Ilioinguinal iliohypogastric nerve blocks—before or after cesarean delivery under spinal anesthesia? Anesth Analg 1996;82:8–12.
references.citation: Orntoft S, Longreen A, Moiniche S, et al. A comparison of pre- and postoperative infiltration with bupivacaine on pain after tonsillectomy. Anaesthesia 1994;94:151–4.
references.citation: Turner GA, Chalkiadis G. Comparison of preoperative with postoperative lignocaine infiltration on postoperative analgesic requirements. Br J Anaesth 1994;72:541–3.
references.citation: Ejlersen E, Andersen HB, Eliasen K, et al. A comparison between preincisional and postincisional lidocaine infiltration and postoperative pain. Anesth Analg 1992;74:495–8.
references.citation: Helmy AK, Ayham B. The effect of the preemptive use of NMDA receptor antagonist dextromethorphan on postoperative analgesic requirements. Anesth Analg 2001;92:739–44.
references.citation: Dahl V, Ernoe PE, Steen T, et al. Does ketamine have preemptive effects in women undergoing abdominal hysterectomy procedures? Anesth Analg 2000;90:1419–22.
references.citation: Menigaux C, Fletcher D, Dupont X, et al. The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair. Anesth Analg 2000;90:129–35.
references.citation: Adam F, Libier M, Oszustowicz T, et al. Preoperative small-dose ketamine has no preemptive analgesic effect in patients undergoing total mastectomy. Anesth Analg 1999;89:444–7.
references.citation: Chia YY, Liu K, Chow LH, Lee TY. Preoperative administration of intravenous dextromethorphan reduces postoperative morphine consumption. Anesth Analg 1999;89:748–52.
references.citation: Wu CT, Yu JC, Yeh CC, et al. Preincisional dextromethorphan treatment decreases postoperative pain and opioid requirement after laparoscopic cholecystectomy. Anesth Analg 1999;88:1331–4.
references.citation: Mathisen LC, Aasbo V, Raeder J. Lack of preemptive analgesic effect of ketamine in laparoscopic cholecystectomy. Acta Anaesthesiol Scand 1999;43:220–4.
references.citation: Reuben SS, Bhopatkar S, Maciolek H, et al. The preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery. Anesth Analg 2002;94:55–9.
references.citation: Priya V, Divatia JV, Sareen R, Upadhye S. Efficacy of intravenous ketoprofen for preemptive analgesia. J Postgrad Med 2002;48:109–12.
references.citation: Norman PH, Daley MD, Lindsey RW. Preemptive analgesic effects of ketorolac in ankle surgery. Anesthesiology 2001;94:599–603.
references.citation: Rosaeg OP, Krepski B, Cicutti N, et al. Effect of preemptive multimodal analgesia for arthroscopic knee ligament repair. Reg Anesth Pain Med 2001;26:125–30.
references.citation: Nagatsuka C, Ichinohe T, Kaneko Y. Preemptive effects of a combination of preoperative diclofenac, butorphanol and lidocaine on postoperative pain management following orthognathic surgery. Anesth Prog 2000;47:119–24.
references.citation: Colbert ST, Hanlon DM, McDonnell C. Analgesia in day case breast biopsy—the value of pre-emptive tenoxicam. Can J Anaesth 1998;45:217–22.
references.citation: Romsing J, Ostergaard D, Larsen SW, Valentin N. Analgesic efficacy and safety of preoperative versus postoperative ketorolac in paediatric tonsillectomy. Acta Anaesthesiol Scand 1998;42:770–5.
references.citation: Hanlon JJ, Muldoon T, Lowry D, at al. Improved postoperative analgesia with preoperative piroxicam. Can J Anaesth 1996;43:102–5.
references.citation: Vanlersberghe C, Lauwers MH, Camu F. Preoperative ketorolac administration has no preemptive analgesic effect for minor oral surgery. Acta Anaesthesiol Scand 1996;40:948–52.
references.citation: Fletcher D, Zetlaoui P, Monin S, at al. Influence of timing on the analgesic effect of intravenous ketorolac after orthopedic surgery. Pain 1995;61:291–7.
references.citation: Rogers JEG, Fleming BG, Macintosh KC, et al. Effect of timing of ketorolac administration on patient-controlled opioid use. Br J Anaesth 1995;75:15–8.
references.citation: Buggy DJ, Wall C, Carton EG. Preoperative or postoperative diclofenac for laparoscopic tubal ligation. Br J Anaesth 1994;73:767–70.
references.citation: Nelson WE, Henderson RC, Almekinders LC, et al. An evaluation of pre- and postoperative nonsteroidal antiinflammatory drugs in patients undergoing knee arthroscopy: a prospective, randomized, double-blinded study. Am J Sports Med 1993;21:510–6.
references.citation: Murphy DF, Medley C. Preoperative indomethacin for pain relief after thoracotomy: comparison with postoperative indomethacin. Br J Anaesth 1993;70:298–300.
references.citation: Sisk AL, Grover BJ. A comparison of preoperative and postoperative naproxen sodium for suppression of postoperative pain. J Oral Maxillofac Surg 1990;48:674–8.
references.citation: Sisk AL, Mosley RO, Martin RP. Comparison of preoperative and postoperative diflunisal for suppression of postoperative pain. J Oral Maxillofac Surg 1989;47:464–8.
references.citation: Doyle E, Bowler GMR. Preemptive effect of multimodal analgesia in thoracic surgery. Br J Anaesth 1998;80:147–51.
references.citation: Millar AY, Mansfield MD, Kinsella J. Influence of timing of morphine administration on postoperative pain and analgesic consumption. Br J Anaesth 1998;81:373–6.
references.citation: Griffin MJ, Hughes D, Knaggs A, et al. Late-onset preemptive analgesia associated with preincisional large-dose alfentanil. Anesth Analg 1997;85:1317–21.
references.citation: Sarantopoulos C, Fassoulaki A. Sufentanil does not preempt pain after abdominal hysterectomy. Pain 1996;65:273–6.
references.citation: Fassoulaki A, Sarantopoulos C, Zotou M, Papoulia D. Preemptive opioid analgesia does not influence pain after abdominal hysterectomy. Can J Anaesth 1995;42:109–13.
references.citation: Wilson RJT, Leith S, Jackson JB, et al. Preemptive analgesia from intravenous administration of opioids: no effect. Anaesthesia 1994;49:591–3.
references.citation: Mansfield M, Meikle R, Miller C. Influence of timing of preoperative alfentanil on postoperative pain and analgesic requirements. Anaesthesia 1994;49:1091–3.
references.citation: Richmond CE, Bromley LM, Woolf CJ. Preoperative morphine preempts postoperative pain. Lancet 1993;342:73–5.
references.citation: Moher D, Jadad AR, Nichol G, Penman M. Assessing the quality of randomized trials: an annotated bibliography of scales and checklists. Control Clin Trials 1995;16:62–73.
references.citation: McQuay HJ. Pre-emptive analgesia. Br J Anaesth 1992;69:1–3.
references.citation: Hogan QH. No preemptive analgesia—is that so bad? Anesthesiology 2002;96:526–7.
references.citation: Seymour RA, Meechan JG, Blair GS. An investigation into post-operative pain after third molar surgery under local analgesia. Br J Oral Maxillofac Surg 1985;23:410–8.
references.citation: Strom BL, Berlin JA, Kinman JL, et al. Parenteral ketorolac and risk of gastrointestinal and operative site bleeding: a postmarketing surveillance study. JAMA 1996;275:376–82.
references.citation: Moiniche S, Romsing J, Dahl JB, Tramer MR. NSAIDs and the risk of operative site bleeding after tonsillectomy: a quantitative systematic review. Anesth Analg 2003;96:68–77.