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Jedna doza intravenskog paracetamola ili intravenskog propacetamola za ublažavanje boli nakon operacije

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Referencias

Abdulla 2012a {published data only}

Abdulla S, Eckhardt R, Netter U, Abdulla W. Efficacy of three IV non‐opioid‐analgesics on opioid consumption for postoperative pain relief after total thyroidectomy: a randomised, double‐blind trial. Middle East Journal of Anesthesiology 2012;21:543‐52. CENTRAL

Abdulla 2012b {published data only}

Abdulla S, Eckhardt R, Netter U, Abdulla W. A randomized, double‐blind, controlled trial on non‐opioid analgesics and opioid consumption for postoperative pain relief after laparoscopic cholecystectomy. Acta Anaesthesiologica Belgica 2012;63:43‐50. CENTRAL

Akarsu 2010 {published data only}

Akarsu S, Sahin S, Kara C, Akdemir N, Degerli S. A comparison between parenteral paracetamol and diclofenac for acute postoperative pain treatment in patients after caeserean section. Journal of Turkish Society of Obstetrics and Gynecology 2010;7:262‐6. CENTRAL

Akil 2014 {published data only}

Akil A, Api O, Bektas Y, Yilmaz AO, Yalti S, Unal O. Paracetamol vs dexketoprofen for perineal pain relief after episiotomy or perineal tear. Journal of Obstetrics & Gynaecology 2014;34:25‐8. CENTRAL

Arici 2009 {published data only}

Arici S, Gurbet A, Turker G, Yavascaoglu B, Sahin S. Preemptive analgesic effects of intravenous paracetamol in total abdominal hysterectomy. Agri Dergisi 2009;21:54‐61. CENTRAL

Arslan 2011 {published data only}

Arslan M, Cicek R, Celep B, lmaz Y, Ustun Kalender H. Comparison of the analgesic effects of intravenous paracetamol and lornoxicam in postoperative pain following thyroidectomies. Agri Dergisi 2011;23:160‐6. CENTRAL

Arslan 2013 {published data only}

Arslan M, Celep B, Cicek R, Kalender HU, Yilmaz H. Comparing the efficacy of preemptive intravenous paracetamol on the reducing effect of opioid usage in cholecystectomy. Journal of Research in Medical Sciences 2013;18:172‐7. CENTRAL

Atef 2008 {published data only}

Atef A, Fawaz AA. Intravenous paracetamol is highly effective in pain treatment after tonsillectomy in adults. European Archives of Oto‐Rhino‐Laryngology 2008;265:351‐5. [17891409]CENTRAL

Aubrun 2003 {published data only}

Aubrun F, Kalfon F, Mottet P, Bellanger A, Langeron O, Coriat P, et al. Adjunctive analgesia with intravenous propacetamol does not reduce morphine‐related adverse effects. British Journal of Anaesthesia 2003;90:314‐9. [PUBMED: 12594143]CENTRAL

Beaussier 2005 {published data only}

Beaussier M, Weickmans H, Paugam C, Lavazais S, Baechle JP, Goater P, et al. A randomized, double‐blind comparison between parecoxib sodium and propacetamol for parenteral postoperative analgesia after inguinal hernia repair in adult patients. Anesthesia & Analgesia 2005;100:1309‐15. [PUBMED: 15845675]CENTRAL

Brodner 2011 {published data only}

Brodner G, Gogarten W, Aken H, Hahnenkamp K, Wempe C, Freise H, et al. Efficacy of intravenous paracetamol compared to dipyrone and parecoxib for postoperative pain management after minor‐to‐intermediate surgery: a randomised, double‐blind trial. European Journal of Anaesthesiology 2011;28:125‐32. CENTRAL

Cakan 2008 {published data only}

Cakan T, Inan N, Culhaoglu S, Bakkal K, Basar H. Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements. Journal of Neurosurgical Anesthesiology 2008;20:169‐73. CENTRAL

Chen 2011 {published data only}

Chen ZF, Jiang H, Li YY. Role of propacetamol in multimodal analgesia after lumbar spine surgery. Journal of Shanghai Jiaotong University (Medical Science) 2011;31:1205‐11. CENTRAL

Dejonckheere 2001 {published data only}

Dejonckheere M, Desjeux L, Deneu S, Ewalenko P. Intravenous tramadol compared to propacetamol for postoperative analgesia following thyroidectomy. Acta Anesthesiologica Belgica 2001;52:29‐33. [PUBMED: 11307656]CENTRAL

Delbos 1995 {published data only}

Delbos A, Boccard E. The morphine‐sparing effect of propacetamol in orthopedic postoperative pain. Journal of Pain & Symptom Management 1995;10:279‐86. [PUBMED: 7541435]CENTRAL

Eremenko 2008 {published data only}

Eremenko AA, Kuslieva EV. Analgesic and opioid‐sparing effects of intravenous paracetamol in the early period after aortocoronary bypass surgery. Anesteziologiia i Reanimatologiia 2008;5:11‐4. CENTRAL

Faiz 2014 {published data only}

Faiz HR, Rahimzadeh P, Visnjevac O, Behzadi B, Ghodraty MR, Nader ND. Intravenous acetaminophen is superior to ketamine for postoperative pain after abdominal hysterectomy: Results of a prospective, randomized, double‐blind, multicenter clinical trial. Journal of Pain Research 2014;7:65‐70. CENTRAL

Farkas 1992 {published data only}

Farkas JC, Larroututou P, Morin JP, Laurian C, Huchet J, Cormier JM, et al. Analgesic efficacy of an injectable acetaminophen versus a dipyrone plus pitofenone plus fenpiverinium association after abdominal aortic repair. Current Therapeutic Research 1992;51:19‐27. CENTRAL

Fletcher 1997 {published data only}

Fletcher D, Negre I, Barbin C, Francois A, Carreres C, Falgueirettes C, et al. Postoperative analgesia with I.V. propacetamol and ketoprofen combination after disc surgery. Canadian Journal of Anaesthesia 1997;44:479‐85. [PUBMED: 9161740]CENTRAL

Hahn 2003 {published data only}

Hahn TW, Mogensen T, Lund C, Jacobsen LS, Hjortsoe NC, Rasmussen SN, et al. Analgesic effect of i.v. paracetamol: possible ceiling effect of paracetamol in postoperative pain. Acta Anaesthesiologica Scandinavica 2003;47:138‐45. [PUBMED: 12631041]CENTRAL

Hans 1993 {published data only}

Hans P, Brichant JF, Bonhomme V, Triffaux M. Analgesic efficiency of propacetamol hydrochloride after lumbar disc surgery. Acta Anesthesiologica Belgica 1993;44:129‐33. [PUBMED: 8116325]CENTRAL

Hiller 2004 {published data only}

Hiller A, Silvanto M, Savolainen S, Tarkkila P. Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy. Acta Anaesthesiologica Scandinavica 2004;48:1185‐9. [PUBMED: 15352967]CENTRAL

Hiller 2012 {published data only}

Hiller A, Helenius I, Nurmi E, Neuvonen PJ, Kaukonen M, Hartikainen T, et al. Acetaminophen improves analgesia but does not reduce opioid requirement after major spine surgery in children and adolescents. Spine 2012;37:E1225‐31. CENTRAL

Hynes 2006 {published data only}

Hynes D, McCarroll M, Hiesse‐Provost O. Analgesic efficacy of parenteral paracetamol (propacetamol) and diclofenac in post‐operative orthopaedic pain. Acta Anaesthesiologica Scandinavica 2006;50:374‐81. [PUBMED: 1648474]CENTRAL

Inal 2006 {published data only}

Inal MT, Celik NS, Tuncay FS. IV paracetamol infusion is better than IV meperidine infusion for postoperative analgesia after Caesarean section. The Internet Journal of Anesthesiology 2006;15. CENTRAL

Jahr 2012 Study 2, 65‐ {published data only}

Jahr JS, Breitmeyer JB, Pan C, Royal MA, Ang RY. Safety and efficacy of intravenous acetaminophen in the elderly after major orthopedic surgery: subset data analysis from 3, randomized, placebo‐controlled trials. American Journal of Therapeutics 2012;19:66‐75. CENTRAL

Jahr 2012 Study 2, 65+ {published data only}

Jahr JS, Breitmeyer JB, Pan C, Royal MA, Ang RY. Safety and efficacy of intravenous acetaminophen in the elderly after major orthopedic surgery: subset data analysis from 3, randomized, placebo‐controlled trials. American Journal of Therapeutics 2012;19:66‐75. CENTRAL

Jahr 2012 Study 3, 65‐ {published data only}

Jahr JS, Breitmeyer JB, Pan C, Royal MA, Ang RY. Safety and efficacy of intravenous acetaminophen in the elderly after major orthopedic surgery: subset data analysis from 3, randomized, placebo‐controlled trials. American Journal of Therapeutics 2012;19:66‐75. CENTRAL

Jahr 2012 Study 3, 65+ {published data only}

Jahr JS, Breitmeyer JB, Pan C, Royal MA, Ang RY. Safety and efficacy of intravenous acetaminophen in the elderly after major orthopedic surgery: subset data analysis from 3, randomized, placebo‐controlled trials. American Journal of Therapeutics 2012;19:66‐75. CENTRAL

Jarde 1997 {published data only}

Jarde O, Boccard E. Parenteral versus oral route increases paracetamol efficacy. Clinical Drug Investigation 1997;14:474‐81. CENTRAL

Juhl 2006 {published data only}

Juhl GI, Norholt SE, Tonnesen E, Hiesse‐Provost O, Jensen TS. Analgesic efficacy and safety of intravenous paracetamol (acetaminophen) administered as a 2 g starting dose following third molar surgery. European Journal of Pain 2006;10:371‐7. [PUBMED: 16085437]CENTRAL

Kamath 2014 {published data only}

Kamath V, Lasrado A. Efficacy of intravenous acetaminophen versus intravenous butorphanol as postoperative analgesic in obstetrics and gynaecology: a comparative study. BJOG: An International Journal of Obstetrics and Gynaecology 2014;121:194. CENTRAL

Kampe 2006 {published data only}

Kampe S, Warm M, Landwehr S, Dagtekin O, Haussmann S, Paul M, et al. Clinical equivalence of IV paracetamol compared to IV dipyrone for postoperative analgesia after surgery for breast cancer. Current Medical Research and Opinion 2006;22:1949‐54. [PUBMED: 17022854]CENTRAL

Kara 2010 {published data only}

Kara C, Resorlu B, Cicekbilek I, Unsal A. Analgesic efficacy and safety of nonsteroidal anti‐inflammatory drugs after transurethral resection of prostate. International Braz J Urol 2010;36(1):49‐54. CENTRAL

Karaman 2010 {published data only}

Karaman Y, Cukurova I, Demirhan E, Gonullu M, Altunbas S. Efficacy of dexketoprofen trometamol for acute postoperative pain relief after ENT surgery: a comparison with paracetamol and metamizole. Nobel Medicus 2010;6:47‐52. CENTRAL

Kemppainen 2006 {published data only}

Kemppainen T, Kokki H, Tuomilehto H, Seppä J, Nuutinen Jl. Acetaminophen is highly effective in pain treatment after endoscopic sinus surgery. Laryngoscope 2006;116:2125‐8. [PUBMED: 17146383]CENTRAL

Khajavi 2007 {published data only}

Khajavi MR, Najafi A, PanahKhahi M, Moharari RS. Propacetamol and morphine in postoperative pain therapy after renal transplantation. International Journal of Pharmacology 2007;3:183‐6. CENTRAL

Khalili 2013 {published data only}

Khalili G, Janghorbani M, Saryazdi H, Emaminejad A. Effect of preemptive and preventive acetaminophen on postoperative pain score: a randomized, double‐blind trial of patients undergoing lower extremity surgery. Journal of Clinical Anesthesia 2013;25:188‐92. CENTRAL

Khan 2007 {published data only}

Khan ZU, Iqbal J, Saleh H, El Deek AM. Intravenous paracetamol is as effective as morphine in knee arthroscopic day surgery procedures. Pakistani Journal of Medical Sciences 2007;26:851‐3. CENTRAL

Kilicaslan 2010 {published data only}

Kilicaslan A, Tuncer S, Yuceaktas A, Uyar M, Reisli R. The effects of intravenous paracetamol on postoperative analgesia and tramadol consumption in cesarean operations. Agri Dergisi 2010;22:7‐12. CENTRAL

Koppert 2006 {published data only}

Koppert W, Frotsch K, Huzurudin H, Boswald W, Griessinger N, Weisbach V, et al. The effects of paracetamol and parecoxib on kidney function in elderly patients undergoing orthopedic surgery. Anesthesia and Analgesia 2006;103:1170‐6. CENTRAL

Korkmaz 2010 {published data only}

Korkmaz Dilmen O, Tunali Y, Cakmakkaya OS, Yentur E, Tutuncu AC, Tureci E, et al. Efficacy of intravenous paracetamol, metamizol and lornoxicam on postoperative pain and morphine consumption after lumbar disc surgery. European Journal of Anaesthesiology 2010;27:428‐32. CENTRAL

Lahtinen 2002 {published data only}

Lahtinen P, Kokki H, Hendolin H, Hakala T, Hynynen M. Propacetamol as adjunctive treatment for postoperative pain after cardiac surgery. Anesthesia & Analgesia 2002;95:813‐9. [12351250]CENTRAL

Landwehr 2005 {published data only}

Landwehr S, Kiencke P, Giesecke T, Eggert D, Thumann G, Kampe S. A comparison between IV paracetamol and IV metamizol for postoperative analgesia after retinal surgery. Current Medical Research and Opinion 2005;21:1569‐75. [PUBMED: 16238896]CENTRAL

Lee 2010 {published data only}

Lee SY, Lee WH, Lee EH, Han KC, Ko YK. The effects of paracetamol, ketorolac, and paracetamol plus morphine on pain control after thyroidectomy. Korean Journal of Pain 2010;23:124‐30. CENTRAL

Leykin 2008 {published data only}

Leykin Y, Casati A, Rapotec A, Dalsasso M, Barzan L, Fanelli G, et al. Comparison of parecoxib and proparacetamol in endoscopic nasal surgery patients. Yonsei Medical Journal 2008;49:383‐8. CENTRAL

Ma 2003 {published data only}

Ma EL, Wang XR, Jiang ZM, Cui Y, Wang R, Liu J. A randomized, double blind, and controlled clinical trial of the non‐addictive propacetamol in postoperative analgesia. Zhongguo Yi Xue Ke Xue Yuan Xue Bao [Acta Acadamiae Medicinae Sinicae] 2003;25:329‐32. [PUBMED: 12905750 ]CENTRAL

Maghsoudi 2014 {published data only}

Maghsoudi R, Etemadian M, Lotfi SMT, Movasagi G, Amjadi M. Opioid sparing effects of intravenous paracetamol after PCNL: a randomized double blinded clinical trial. Journal of Endourology 2012;26:A354. CENTRAL
Maghsoudi R, Tabatabai M, Radfar MH, Movasagi G, Etemadian M, Shati M, et al. Opioid‐sparing effect of intravenous paracetamol after percutaneous nephrolithotomy: a double‐blind randomized controlled trial. Journal of Endourology 2014;28:23‐7. CENTRAL

Marty 2005 {published data only}

Marty J, Benhamou D, Chassard D, Empairaire N, Roche A, Mayaud A, et al. Effects of single‐dose injectable paracetamol versus propacetamol in pain management after minor gynecologic surgery: a multicenter, randomized, double‐blind, active‐controlled, two‐parallel‐group study. Current Therapeutic Research 2005;66:294‐306. CENTRAL

Mimoz 2001 {published data only}

Mimoz O, Incagnoli P, Gillon MC, Kuhlman L, Mirand A, Soilleux H, et al. Analgesic efficacy and safety of nefopam vs. propacetamol following hepatic resection. Anaesthesia 2001;51:520‐5. CENTRAL

Mitra 2012 {published data only}

Mitra S, Khandelwal P, Sehgal A. Diclofenac‐tramadol vs. diclofenac‐acetaminophen combinations for pain relief after caesarean section. Acta Anaesthesiologica Scandinavica 2012;56:706‐11. CENTRAL

Moller 2005a {published data only}

Moller PL, Juhl GI, Payen‐Champenois C, Skoglund LA. Intravenous acetaminophen (paracetamol): comparable analgesic efficacy, but better local safety than its prodrug, propacetamol, for postoperative pain after third molar surgery. Anesthesia & Analgesia 2005;101:90‐6. CENTRAL

Moller 2005b {published data only}

Moller PL, Sindet‐Pedersen S, Petersen CT, Juhl GI, Dillenschneider A, Skoglund LA. Onset of acetaminophen analgesia: comparison of oral and intravenous routes after third molar surgery. British Journal of Anaesthesia 2005;94:642‐8. CENTRAL

Mowafi 2012 {published data only}

Mowafi HA, Elmakarim EA, Ismail S, Al‐Mahdy M, El‐Saflan AE, Elsaid AS. Intravenous lornoxicam is more effective than paracetamol as a supplemental analgesic after lower abdominal surgery: a randomized controlled trial. World Journal of Surgery 2012;36:2039‐44. CENTRAL

Ohnesorge 2009 {published data only}

Ohnesorge H, Bein B, Hanss R, Francksen H, Mayer L, Scholz J, et al. Paracetamol versus metamizol in the treatment of postoperative pain after breast surgery: a randomized, controlled trial. European Journal of Anaesthesiology 2009;26:648‐53. CENTRAL

Omar 2011 {published data only}

Omar AAA, Al Issa KA. Intravenous paracetamol (Perfalgan) for analgesia after cesarean section: a double‐blind randomized controlled study. Rawal Medical Journal 2011;36:1‐12. CENTRAL

Oncul 2011 {published data only}

Oncul AM, Cimen E, Kucukyavuz Z, Cambazoglu M. Postoperative analgesia in orthognathic surgery patients: diclofenac sodium or paracetamol?. British Journal of Oral & Maxillofacial Surgery 2011;49:138‐41. CENTRAL

Oreskovic 2014 {published data only}

Oreskovic Z, Bicanic G, Hrabac P, Tripkovic B, Delimar D. Treatment of postoperative pain after total hip arthroplasty: comparison between metamizol and paracetamol as adjunctive to opioid analgesics ‐ Prospective, double‐blind, randomised study. Archives of Orthopaedic & Trauma Surgery 2014;134:631‐6. CENTRAL

Paech 2014 {published data only}

Paech MJ, McDonnell NJ, Sinha A, Baber C, Nathan EA. A randomised controlled trial of parecoxib, celecoxib and paracetamol as adjuncts to patient‐controlled epidural analgesia after caesarean delivery. Anaesthesia & Intensive Care 2014;42:15‐22. CENTRAL

Peduto 1998 {published data only}

Peduto VA, Ballabio M, Stefanini S. Efficacy of propacetamol in the treatment of postoperative pain. Morphine‐sparing effect in orthopedic surgery. Italian Collaborative Group on Propacetamol. Acta Anaesthesiologica Scandinavica 1998;42:293‐8. [PUBMED: 9542555]CENTRAL

Salonen 2009 {published data only}

Salonen A, Silvola J, Kokki H. Does 1 or 2 g paracetamol added to ketoprofen enhance analgesia in adult tonsillectomy patients?. Acta Anaesthesiologica Scandinavica 2009;53:1200‐6. CENTRAL

Sanyal 2014 {published data only}

Sanyal P, Pal A, Biswas J, Mukhopadhyay P, Dasgupta S, Das SH. Choice of non‐opioid analgesics for postoperative analgesia in patients undergoing lower abdominal gynecological surgeries. BJOG: An International Journal of Obstetrics and Gynaecology 2014;121:189. CENTRAL

Shimia 2014 {published data only}

Shimia M, Parish M, Abedini N. The effect of intravenous paracetamol on postoperative pain after lumbar discectomy. Asian Spine Journal 2014;8:400‐4. CENTRAL

Siddik 2001 {published data only}

Siddik SM, Aouad MT, Jalbout MI, Rizk LB, Kamar GH, Baraka AS. Diclofenac and/or propacetamol for postoperative pain management after cesarean delivery in patients receiving patient controlled analgesia morphine. Regional Anesthesia and Pain Medicine 2001;26:310‐5. CENTRAL

Sinatra 2005 {published data only}

Sinatra RS, Jahr JS, Reynolds L, Groudine SB, Royal MA, Breitmeyer JB, et al. Intravenous acetaminophen for pain after major orthopedic surgery: an expanded analysis. Pain Practice 2012;12:357‐65. CENTRAL
Sinatra RS, Jahr JS, Reynolds LW, Viscusi ER, Groudine SB, Payen‐Champenois C. Efficacy and safety of single and repeated administration of 1 gram intravenous acetaminophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology 2005;102:822‐31. [PUBMED: 15791113]CENTRAL

Tiippana 2008 {published data only}

Tiippana E, Bachmann M, Kalso E, Pere P. Effect of paracetamol and coxib with or without dexamethasone after laparoscopic cholecystectomy. Acta Anaesthesiologica Scandinavica 2008;52:673‐80. CENTRAL

Togrul 2011 {published data only}

Togrul T, Baysal Yildirim Z, Cengiz M, Cigdem A, San I, Kar M. Comparison of intravenous paracetamol and tramadol for postoperative analgesia in patients with septo‐rhinoplasty. Anestezi Dergisi 2011;19:213‐6. CENTRAL

Tunali 2013 {published data only}

Tunali Y, Akcil EF, Dilmen OK, Tutuncu AC, Koksal GM, Akbas S, et al. Efficacy of intravenous paracetamol and dexketoprofen on postoperative pain and morphine consumption after a lumbar disk surgery. Journal of Neurosurgical Anesthesiology 2013;25:143‐7. CENTRAL

Tuncel 2012 {published data only}

Tuncel A, Balci M, Postaci A, Aslan Y, Koseoglu E, Sacan O, et al. Comparison of intraoperative local levobupivacaine infiltraton anaesthesia, intravenous paracetamol and lornoxicam treatments for postoperative pain management in patients underwent transperitoneal laparoscopic renal and adrenal surgery. Journal of Endourology 2012;26:A287. CENTRAL

Unal 2013 {published data only}

Unal C, Cakan T, Baltaci B, Basar H. Comparison of analgesic efficacy of intravenous paracetamol and intravenous dexketoprofen trometamol in multimodal analgesia after hysterectomy. Journal of Research in Medical Sciences 2013;18:897‐903. CENTRAL

Van Aken 2004 {published data only}

Van Aken H, Thys L, Veekman L, Buerkle H. Assessing analgesia in single and repeated administrations of propacetamol for postoperative pain: comparison with morphine after dental surgery. Anesthesia & Analgesia 2004;98:159‐65. [PUBMED: 14693612]CENTRAL

Varrassi 1999 {published data only}

Varrassi G, Marinangeli F, Agro F, Aloe L, De Cillis P, De Nicola A, et al. A double‐blinded evaluation of propacetamol versus ketorolac in combination with patient‐controlled analgesia morphine: analgesic efficacy and tolerability after gynecologic surgery. Anesthesia & Analgesia 1999;88:611‐6. [PUBMED: 10072016]CENTRAL

Vuilleumier 1998 {published data only}

Vuilleumier PA, Buclin T, Biollaz J. Comparison of propacetamol and morphine in postoperative analgesia. Schweizerische Medizinische Wochenschrift 1998;14:259‐63. [9540151]CENTRAL

Wininger 2010 {published data only}

Wininger SJ, Miller H, Minkowitz HS, Royal MA, Ang RY, Breitmeyer JB, et al. A randomized, double‐blind, placebo‐controlled, multicenter, repeat‐dose study of two intravenous acetaminophen dosing regimens for the treatment of pain after abdominal laparoscopic surgery. Clinical Therapeutics 2010;32:2348‐69. CENTRAL

Zhou 2001 {published data only}

Zhou TJ, Tang J, White PF. Propacetamol versus ketorolac for treatment of acute postoperative pain after total hip or knee replacement. Anesthesia & Analgesia 2001;92:1569‐75. [PUBMED: 11375848]CENTRAL

Alhashemi 2006 {published data only}

Alhashemi JA, Daghistani MF. Effects of intraoperative I.V. acetaminophen vs I.M. meperidine on post‐tonsillectomy pain in children. British Journal of Anaesthesia 2006;96:790‐5. [PUBMED: 16613928]CENTRAL

Alhashemi 2007 {published data only}

Alhashemi JA, Daghistani MF. Effect of intraoperative intravenous acetaminophen vs. intramuscular meperidine on pain and discharge time after paediatric dental restoration. European Journal of Anaesthesiology 2007;24:128‐33. [PUBMED: 16895621]CENTRAL

Alimian 2014 {published data only}

Alimian M, Pournajafian A, Kholdebarin, Ghodraty M, Rokhtabnak F, Yazdkhasti P. Analgesic effects of paracetamol and morphine after elective laparotomy surgeries. Anesthesiology & Pain Medicine 2014;4:e12912. CENTRAL

Anand 2013 {published data only}

Anand A, Sprenker CJ, Karlnoski R, Norman J, Miladinovic B, Wilburn B, et al. Intravenous acetaminophen vs. ketorolac for postoperative analgesia after ambulatory parathyroidectomy. Scandinavian Journal of Pain 2013;4:249‐53. CENTRAL

Ang 1990 {published data only}

Ang ET, Goldfarb G, Boccard E. Analgesic efficacy of propacetamol hydrochlorate 2 g versus pentazocine 30 mg after orthopedic surgery. European Journal of Pain 1990;11:137‐42. CENTRAL

Ashrafnejad 2012 {published data only}

Ashrafnejad B, Hassani V. Comparison between analgesic effect of morphine and propacetamol after orthopedic surgeries. Pain Practice 2012;12:123. CENTRAL

Aydogan 2008 {published data only}

Aydogan H, Dogru K, Erdem S, Bicer C, Aksu R, Boyaci A. The effect of IV paracetamol on the hemodynamic indices, liver functions and the postoperative analgesia in the patients underwent major orthopaedic surgery. Erciyes Tip Dergisi [Erciyes Medical Journal] 2008;30:71‐7. CENTRAL

Caliskan 2013 {published data only}

Caliskan E, Sener M, Kocum A, Ozyilkan NB, Ezer SS, Aribogan A. The efficacy of intravenous paracetamol versus dipyrone for postoperative analgesia after day‐case lower abdominal surgery in children with spinal anesthesia: a prospective randomized double‐blind placebo‐controlled study. BMC Anesthesiology 2013;13:1‐8. CENTRAL

Candiotti 2010 {published data only}

Candiotti KA, Bergese SD, Viscusi ER, Singla SK, Royal MA, Singla NK. Safety of multiple‐dose intravenous acetaminophen in adult inpatients. Pain Medicine 2010;11:1841‐8. CENTRAL

Cok 2011 {published data only}

Cok OY, Eker HE, Pelit A, Canturk S, Akin S, Aribogan A, et al. The effect of paracetamol on postoperative nausea and vomiting during the first 24 h after strabismus surgery: a prospective, randomised, double‐blind study. European Journal of Anaesthesiology 2011;28:836‐41. CENTRAL

Dowling 2014 {published data only}

Dowling O, Campese C, Macchio F, Aronsohn J, Gold J, Bosshart D, et al. Effect of single dose IV acetaminophen on postoperative/postdischarge nausea and vomiting, pain, and patient satisfaction in outpatients undergoing laparoscopic cholecystectomy. Anesthesia and Analgesia 2014;118:S29. CENTRAL

Elseify 2011 {published data only}

Elseify ZA, El‐Khattab SO, Khattab AM, Atta EM, Aijoub LF. Combined parecoxib and I.V. paracetamol provides additional analgesic effect with better postoperative satisfaction in patients undergoing anterior cruciate ligament reconstruction. Saudi Journal of Anaesthesia 2011;5:45‐9. CENTRAL

Fijalkowska 2006 {published data only}

Fijalkowska A, Trela‐Stachurska K, Rechberger T. Efficacy of intravenous paracetamol for early postoperative analgesia after gynaecological surgery. Anaesthesiology Intensive Therapy 2006;38:66‐8. CENTRAL

Fourcade 2005 {published data only}

Fourcade O, Sanchez P, Kern D, Mazoit JX, Minville V, Samii K. Propacetamol and ketoprofen after thyroidectomy. European Journal of Anaesthesiology 2005;22:373‐7. [PUBMED: 15918387]CENTRAL

Garcia 1999 {published data only}

Garcia F, Rodriguez‐Huertas F, Gutierrez M, Bustos A, Sariego M, Garcia‐ Baquero A. Preoperative propacetamol and postoperative pain after laparoscopic surgery for tubal blockage. Revista de la Sociedad Espanola del Dolor 1999;6:83‐7. CENTRAL

Gehling 2010 {published data only}

Gehling M, Arndt C, Eberhart LHJ, Koch T, Kruger T, Wulf H. Postoperative analgesia with parecoxib, acetaminophen, and the combination of both: a randomized, double‐blind, placebo‐controlled trial in patients undergoing thyroid surgery. British Journal of Anaesthesia 2010;104:761‐7. CENTRAL

Ghaffaripour 2012 {published data only}

Ghaffaripour JS, Mahmoudi H, Lahsaee S, Jaafari H, Kazemi AP, Mirshamsi M. Comparison of propacetamol and morphine in postoperative pain relief after orthopedic surgery. Pain Practice 2012;12:129. CENTRAL

Gousheh 2013 {published data only}

Gousheh SM, Nesioonpour S, Javaher Foroosh F, Akhondzadeh R, Sahafi SA, Alizadeh Z. Intravenous paracetamol for postoperative analgesia in laparoscopic cholecystectomy. Anesthesiology & Pain Medicine 2013;3:214‐8. CENTRAL

Granry 1997 {published data only}

Granry JC, Rod B, Monrigal JP, Merckx J, Berniere J, Jean N, et al. The analgesic efficacy of an injectable prodrug of acetaminophen in children after orthopaedic surgery. Paediatric Anaesthesia 1997;7:445‐9. [PUBMED: 9365969]CENTRAL

Grundmann 2006 {published data only}

Grundmann U, Wornle C, Biedler A, Kreuer S, Wrobel M, Wilhelm W. The efficacy of the non‐opioid analgesics parecoxib, paracetamol and metamizol for postoperative pain relief after lumbar microdiscectomy. Anesthesia & Analgesia 2006;103:217‐22. [PUBMED: 16790656]CENTRAL

Hernandez Palazon 2001 {published data only}

Hernandez‐Palazon J, Tortosa JA, Martinez‐Lage JF, Perez‐Flores D. Intravenous administration of propacetamol reduces morphine consumption after spinal fusion surgery. Anesthesia & Analgesia 2001;92:1473‐6. [PUBMED: 11375828]CENTRAL

Irct2012062410102N {published data only}

IRCT2012062410102N1. A comparison of analgesic effect of intravenous acetaminophen (Apotel) versus oxycodone tablet and oral acetaminophen codeine in rhinoplasty and septoplasty surgery. irct.ir/searchresult.php?keyword=A%20comparison%20of%20analgesic%20effect%20of%20Intravenous%20Acetaminophen%20&id=10102&number=1&field=g&prt=1&total=1&m=1 (accessed 24 March 2015). CENTRAL

Ko 2010 {published data only}

Ko MJ, Lee JH, Cheong SH, Shin CM, Kim YJ, Choe YK, et al. Comparison of the effects of acetaminophen to ketorolac when added to lidocaine for intravenous regional anesthesia. Korean Journal of Anesthesiology 2010;58:357‐61. CENTRAL

Kocum 2013 {published data only}

Kocum AI, Sener M, Caliskan E, Bozdogan N, Micozkadioglu D, Yilmaz I, et al. Intravenous paracetamol and dipyrone for postoperative analgesia after day‐case tonsillectomy in children: a prospective, randomized, double blind, placebo controlled study. Revista Brasileira de Otorrinolaringologia 2013;79:89‐94. CENTRAL

Memis 2010 {published data only}

Memis D, Inal MT, Kavalci G, Sezer A, Sut N. Intravenous paracetamol reduced the use of opioids, extubation time, and opioid‐related adverse effects after major surgery in intensive care unit. Journal of Critical Care 2010;25:458‐62. CENTRAL

Murat 2005 {published data only}

Murat I, Baujard C, Foussat C, Guyot E, Petel H, Rod B, et al. Tolerance and analgesic efficacy of a new i.v. paracetamol solution in children after inguinal hernia repair. Paediatric Anaesthesia 2005;15:663‐70. CENTRAL

NCT01691690 {published data only}

NCT01691690. Analgesic effect of single dose intravenous acetaminophen in pediatric patients undergoing tonsillectomy. clinicaltrials.gov/ct2/show/NCT01691690 (accessed 24 March 2015). CENTRAL

NCT01721486 {published data only}

NCT01721486. Efficacy of iv vs oral administration of acetaminophen for pain control following tonsillectomy with or without adenoidectomy. clinicaltrials.gov/ct2/show/NCT01721486 (accessed 24 March 2015). CENTRAL

Nikoda 2006 {published data only}

Nikoda VV, Makarova VV, Maiachkin RB, Bondarenko AV. Clinical aspects of analgesia with intravenous paracetamol in the early postoperative period. Anesteziologiia i Reanimatologiia 2006;6:54‐8. CENTRAL

Olonisakin 2012 {published data only}

Olonisakin RP, Amanor‐Boadu SD, Akinyemi AO. Morphine‐sparing effect of intravenous paracetamol for post operative pain management following gynaecological surgery. African Journal of Medicine & Medical Sciences 2012;31:429‐36. CENTRAL

Pernia 2000 {published data only}

Pernia A, Torres LM, Calderon E. Management of postoperative pain through intravenous patient controlled analgesia (iv PCA) versus propacetamol and metamizol. Revista de la Sociedad Espanola del Dolor 2000;7:354‐60. CENTRAL

Rashwan 2013 {published data only}

Rashwan D, Fathy El‐Rahmawy G. Multimodal analgesia after upper limb orthopedic surgeries: patient controlled intravenous low dose tramadol analgesia with or without intravenous acetaminophen ‐ a comparative study. Egyptian Journal of Anaesthesia 2013;29:231‐4. CENTRAL

Silvanto 2007 {published data only}

Silvanto M, Munsterhjelm E, Savolainen S, Tiainen P, Niemi T, Ylikorkala O, et al. Effect of 3 g of intravenous paracetamol on post‐operative analgesia, platelet function and liver enzymes in patients undergoing tonsillectomy under local anaesthesia. Acta Anaesthesiologica Scandinavica 2007;51:1147‐54. [PUBMED: 17711562]CENTRAL

Topal 2009 {published data only}

Topal A, Erol A, Tuncer, S, Tavlan A, Kilicaslan A, Otelcioglu S. The effect of intravenous paracetamol on postoperative analgesia and morphine consumption. Anestezi Dergisi 2009;17:29‐32. CENTRAL

Toygar 2008 {published data only}

Toygar P, Akkaya T, Ozkan D, Ozel O, Uslu E, Gumus H. Does iv paracetamol have preemptive analgesic effect on lumber disc surgeries?. Agri Dergisi 2008;20:14‐9. CENTRAL

Turner 2014 {published data only}

Turner L. The impact of IV acetaminophen on postoperative pain in women undergoing pelvic organ prolapse repair: a double‐blind randomized placebo controlled trial. https://clinicaltrials.gov/show/NCT021557382014. CENTRAL

Uvarov 2008 {published data only}

Uvarov DN, Orlov MM, Levin AV, Sokolov AV, Nedashkovskii EV. Role of paracetamol in a balanced postoperative analgesia scheme after thoracotomy. Anesteziologiia i Reanimatologiia 2008;4:46‐9. CENTRAL

Uzun 2010 {published data only}

Uzun S, Aycan IO, Erden IA, Sahin A, Aypar U. The addition of metamizole to morphine and paracetamol improves early postoperative analgesia and patient satisfaction after lumbar disc surgery. Turkish Neurosurgery 2010;20:341‐7. CENTRAL

Verchere 2002 {published data only}

Verchere E, Grenier B, Mesli A, Siao D, Sesay M, Maurette P. Postoperative pain management after supratentorial craniotomy. Journal of Neurosurgical Anesthesiology 2002;14:96‐101. [PUBMED: 11907388]CENTRAL

Zeidan 2014 {published data only}

Zeidan A, Mazoit JX, Ali Abdullah M, Maaliki H, Ghattas T, Saifan A. Median effective dose (ED50) of paracetamol and morphine for postoperative pain: a study of interaction. British Journal of Anaesthesia 2014;112:118‐23. CENTRAL

Ziolkowski 2008 {published data only}

Ziolkowski R, Srebrzynski A, Kaczka K, Butwicka A, Kuzdak K, Pomorski L. Assessment of postoperative analgesia using intravenous paracetamol during first day following thyroid surgery for goiter. Clinical and Experimental Medical Letters 2008;49:41‐6. CENTRAL

References to studies awaiting assessment

Atashkhoyi 2014 {published data only}

Atashkhoyi S, Rasouli S, Fardiazar Z, Ghojazadeh M, Marandi PH. Preventive analgesia with intravenous paracetamol for post‐cesarean section pain control. International Journal of Women's Health and Reproduction Sciences 2014;2:131‐7. CENTRAL

Dawoodi 2014 {published data only}

Dawoodi I, Khety Z. Comparative efficacy and safety study of analgesic effect of fentanyl I.V. and paracetamol I.V. in postoperative patients in multidisciplinary hospital. Research Journal of Pharmaceutical, Biological and Chemical Sciences 2014;5:664‐8. CENTRAL

Jabalameli 2014 {published data only}

Jabalameli M, Goudarzi L. Preventive effects of intravenous paracetamol in post‐partum pain of elective cesarean delivery with spinal anesthesia. Journal of Isfahan Medical School 2014;32:1227‐37. CENTRAL

Majumdar 2014 {published data only}

Majumdar S, Das A, Kundu R, Mukherjee D, Hazra B, Mitra T. Intravenous paracetamol infusion: superior pain management and earlier discharge from hospital in patients undergoing palliative head‐neck cancer surgery. Perspectives in Clinical Research 2014;5:172‐7. CENTRAL

Pekmezci 2014 {published data only}

Pekmezci A, Cesur M, Aksoy M, Ince I, Aksoy AN. The effect of ilioinguinal‐iliohypogastric block with or without intravenous paracetamol for pain relief after caesarean delivery. Acta Medica Mediterranea 2014;30:1183‐8. CENTRAL

Rasheed 2007 {published data only}

Borodiciene J, Gudaityte J, Gerulyte I, Macas A, Suskeviciene I. Randomized controlled study of the acetaminophen effectiveness after adenotonsillectomy or tonsillectomy in children. European Journal of Anaesthesiology 2014;31:173. CENTRAL
Dabir S, Parsa T, Abbasinazari M, Parviz Y. Comparison of a single dose of intravenous paracetamol with single dose of rectal indomethacin for pain management after open septorhinoplasty surgery. La Prensa Medica 2016;102:1. CENTRAL
Rasheed A, Aqil M, Haq A, Usman SK. Comparative study of tramadol & propacetamol for postoperative pain management in patients undergoing nasal surgeries. Medical Forum Monthly 2007;18:21‐5. CENTRAL

Ritchie 2015 {published data only}

Ritchie R, Sloan PA, Reddy A, Chau D, Lukens MF, Nimma S. Intraoperative acetaminophen for pediatric post‐tonsillectomy pain relief: a comparison of 2 surgical techniques. Anesthesia and Analgesia 2015;120:S225. CENTRAL

Singla 2015 {published data only}

Singla NK, Hale ME, Davis JC, Bekker A, Gimbel J, Jahr J, et al. IV acetaminophen: Efficacy of a single dose for postoperative pain after hip arthroplasty: subset data analysis of 2 unpublished randomized clinical trials. American Journal of Therapeutics 2015;22:2‐10. CENTRAL

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Anderson 2005

Anderson BJ, Pons G, Autret‐LecaE, Allegaert K, Boccard E. Pediatric intravenous paracetamol (propacetamol) pharmacokinetics: a population analysis. Paediatric Anaesthesia 2005;15:282‐92. [MEDLINE: 15787918]

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Apfel CC, Turan F, Souza K, Pergolizzi J, Hornuss C. Intravenous acetaminophen reduces postoperative nausea and vomiting: a systematic review and metaanalysis. Pain 2013;154:677‐89.

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References to other published versions of this review

Tzortzopoulou 2011

Tzortzopoulou A, McNicol ED, Cepeda MS, Francia MBD, Farhat T, Schumann R. Single dose intravenous propacetamol or intravenous paracetamol for postoperative pain. Cochrane Database of Systematic Reviews 2011, Issue 10. [DOI: 10.1002/14651858.CD007126.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Abdulla 2012a

Methods

Double‐blind, placebo and active‐controlled, multiple dose, over 24 h

First dose administered 15 min prior to extubation

Participants

Type of surgery: thyroidectomy

Paracetamol group

Entered/completing: 30/30

Age (mean, SD): 44.5 ± 15.1

Sex (male, %): 16.7%

Placebo

Entered/completing: 30/30

Age (mean, SD): 47.9 ± 11.8

Sex (male, %): 10.0%

Parecoxib

Entered/completing: 30/30

Age (mean, SD): 48.3 ± 14.2

Sex (male, %): 23.3%

Metamizole

Entered/completing: 30/30

Age (mean, SD): 43.8 ± 13.7

Sex (male, %): 16.7%

Interventions

1 g paracetamol in 100 ml normal saline over 15 min

Placebo, parecoxib 40 mg, or metamizole 1 g: all in 100 ml NS over 15 min

Outcomes

Primary: accumulated opioid consumption (piritramide via PCA)

Secondary:

Pain intensity (VAS)

Pain relief (VRS)

Patient satisfaction (VRS)

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes

Details of preoperative pain

Participants with chronic pain were excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomization (http://www.randomization.com)

Allocation concealment (selection bias)

Low risk

Sealed, opaque envelope, only opened in emergency

Blinding (performance bias and detection bias)
All outcomes

Low risk

“The study solutions were clear so that they could not be recognized by the anesthesiologists collecting the data and were prepared by one of the researchers who was not involved in the intraoperative and postoperative treatment of these patients”.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts or protocol violations – complete data set obtained for all 4 groups

Selective reporting (reporting bias)

Unclear risk

All outcomes from Methods section reported in Results section, but side effects not monitored adequately

Size

High risk

Fewer than 50 participants per arm of the study (30 paracetamol, 30 placebo, 30 parecoxib, 30 metamizole)

Abdulla 2012b

Methods

Double‐blind, placebo and active‐controlled, multiple dose, over 24 h

First dose administered 15 min prior to extubation

Participants

Type of surgery: laparoscopic cholecystectomy

Paracetamol group

Entered/completing: 30/30

Age (mean, SD): 52.5 ± 15.8

Sex (male, %): 23.3%

Placebo

Entered/completing: 30/30

Age (mean, SD): 47.1 ± 13.9

Sex (male, %): 20.0%

Parecoxib

Entered/completing: 30/30

Age (mean, SD): 54.9 ± 13.0

Sex (male, %): 26.7%

Metamizole

Entered/completing: 30/30

Age (mean, SD): 52.4 ± 15.6

Sex (male, %): 30.0%

Interventions

1 g paracetamol in 100 ml normal saline over 15 min

Placebo, parecoxib 40 mg, or metamizole 1 g: all in 100 ml NS over 15 min

Outcomes

Primary: accumulated opioid consumption (piritramide via PCA)

Secondary:

Pain intensity (VAS)

Pain relief (VRS)

Patient satisfaction (VRS)

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes

Details of preoperative pain

Participants with chronic pain were excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomization (http://www.randomization.com)

Allocation concealment (selection bias)

Low risk

The group assignment code was retained until the conclusion of the study

Blinding (performance bias and detection bias)
All outcomes

Low risk

“The study solutions were prepared by one of the researchers who were not involved in the intraoperative and postoperative treatment of these patients. Postoperative data were collected by anesthesiologists who were blinded as to the treatment used. Other caretakers were also unaware of the analgesic drug that would be used for each patient during the study”.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts or protocol violations – complete data set obtained for all 4 groups

Selective reporting (reporting bias)

Unclear risk

All outcomes from Methods section reported in Results section, but side effects not monitored adequately and satisfaction score results not fully described

Size

High risk

Fewer than 50 participants per arm of the study (30 paracetamol, 30 placebo, 30 parecoxib, 30 metamizole)

Akarsu 2010

Methods

Randomized, double‐blind, parallel, active‐controlled. Pain evaluated up to 6 h after dose administered.

Participants

Type of surgery: cesarean section

Paracetamol group

Entered/completing: 40/unclear

Age (mean, SD): 24.2 ± 1.1

Sex (male, %): 0

Control group

Entered/completing: 40/unclear

Age (mean, SD): 24.4 ± 1.2

Sex (male, %): 0

Interventions

Paracetamol 1 g IV over 15 min at first complaint of pain

Diclofenac 75 mg IM as above

Outcomes

Primary: time to first rescue analgesic (1 mg/kg IM pethidine)

Secondary: VAS pain scores at 30 min, 1, 2, 4 and 6 h; adverse events

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes ‐ all P values > 0.05: demographic characteristics, week of pregnancy, newborn's weight, Apgar scores, operation time, time to first postoperative analgesic requirement

Details of preoperative pain

Participants with previous continuous analgesic use were excluded

Notes

Translated from Turkish using Google Translate

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Used envelopes to randomly divide 2 groups – no additional details given

Allocation concealment (selection bias)

Unclear risk

No details

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

No details but stated as double‐blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No mention of participants dropping out

Selective reporting (reporting bias)

Low risk

All outcomes in Methods section reported in Results

Size

High risk

Fewer than 50 participants per arm of the study (40 paracetamol, 40 diclofenac)

Akil 2014

Methods

Parallel, double‐blind, double dummy, active‐controlled study

Interventions administered 5 min after perineal repair and at 6 h

Participants

Type of surgery: repair of episiotomy or perineal tear post vaginal delivery using cut and suturing

Paracetamol group

Entered/completing: 46/41

Age (mean, SD): 24.71 ± 4.91

Sex (male, %): 0

Control group

Entered/completing: 49/41

Age (mean, SD): 24.71 ± 5.83

Sex (male, %): 0

Interventions

Paracetamol 1 g/100 ml via slow infusion q6 x 2 doses

Dexketoprofen 50 mg IV also via slow infusion q6 x 2 doses

Outcomes

Primary: VAS (0 to 10 0 to 100?) scores at 1 h

Secondary: VAS at 6 and 12 h, adverse events. VAS at 2 and 3 also measured and reported, but not listed as outcomes.

Source of funding

Not reported

Were treatment groups comparable at baseline?

Only difference was gravidity (P value = 0.02). No significant differences in sociodemographic data or baseline parameters (parity, age, the length of the labour, birth weight, dose of the local anesthetic used during the repair of episiotomy or perineal tears (lidocaine) and VAS 0.

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“Block randomization was achieved by using a computer‐generated random number chart”

Allocation concealment (selection bias)

Low risk

“Consecutive numbers generated by the computer were written on the numbered opaque envelopes, which were sealed by someone other than those involved in the study”

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Described as blinded, but no details other than that participants in both of the groups had also placebo injections mimicking the active drug

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

1 participant in paracetamol group and 2 participants in dexketoprofen group not included in final analysis due to incomplete data.

4 participants in paracetamol group and 6 in dexketoprofen group excluded due to need for extra analgesic. Despite flow chart, unclear if these participants were excluded before or after receiving interventions.

Selective reporting (reporting bias)

Low risk

Adverse events assessed but reported that none occurred in any participant

Size

High risk

Fewer than 50 participants per arm of the study (46 paracetamol, 49 dexketoprofen)

Arici 2009

Methods

Randomized, double‐blind, active‐ and placebo‐controlled

Medications administered prior to skin closure

Participants

Type of surgery: elective total abdominal hysterectomy by laparotomy

Paracetamol group

Entered/completing: 30/27

Age (mean, SD): 47.73 ± 7.20

Sex (male, %): 0

Placebo group

Entered/completing: 30/27

Age (mean, SD): 49.90 ± 6.40

Sex (male, %): 0

Interventions

Intervention: paracetamol 1 g/100 ml IV at skin closure

Placebo: normal saline 100 ml

Third group received paracetamol preemptively (not included in analysis)

Outcomes

Pain intensity at rest and movement (VAS)

Opioid consumption (morphine)

All other outcomes reported at 24 h only

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: age, height, weight, ASA status, time of operation

Details of preoperative pain

Not reported

Notes

Preemptive group had lower morphine consumption versus postsurgical group at all time intervals post 2 to 4 h

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not described

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Same number of dropouts in both groups (n = 3), but reasons for dropouts not given

Selective reporting (reporting bias)

Low risk

Full reporting of primary outcome data, some secondary outcomes listed only as "no significant difference"

Size

High risk

Fewer than 50 participants per arm of the study (30 paracetamol, 30 placebo)

Arslan 2011

Methods

Double‐blind, placebo and active‐controlled, single dose, over 24 h

Interventions administered at end of procedure

Participants

Type of surgery: thyroidectomy

Paracetamol group

Entered/completing: 20/20

Age (mean, SD): 49.2 ± 13.3

Sex (male, %): 10.0%

Lornoxicam group

Entered/completing: 20/20

Age (mean, SD): 43.9 ± 9.5

Sex (male, %): 20.0%

Placebo group

Entered/completing: 20/20

Age (mean, SD): 48.7 ± 12.3

Sex (male, %): 15.0%

Interventions

Paracetamol 1 g over 10 min

Lornoxicam 8 mg or placebo (100 ml NS) over 10 min

Outcomes

Primary: analgesic consumption (tramadol, n/N) at 0 to 6, 6 to 12 and 12 to 24 h and mg total

Secondary:

VAS pain scores at 15 min, and 1, 2, 4, 6, 8, 12, 18, and 24 h postoperatively

Time to first request for analgesia

Adverse events

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes

Details of preoperative pain

Patients using analgesics long‐term were excluded from the study

Notes

Translated from Turkish

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Withdrawal of a card. No further details.

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Appears that all participants completed the study and that all data were collected

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

60 participants (20 paracetamol, 20 placebo, 20 lornoxicam)

Arslan 2013

Methods

Randomized, placebo‐controlled, single dose, over 24 h

Interventions administered preemptively (not included in this review) or at end of surgery

Participants

Type of surgery: elective lap cholecystectomy

Paracetamol group

Entered/completing: 100/100

Age (mean, SD): 41.5 ± 7.8

Sex (male, %): 32

Control group

Entered/completing: 100/100

Age (mean, SD): 44.5 ± 6.5

Sex (male, %): 34

Interventions

Paracetamol 1 g/100 ml IV over 10 min

Placebo: saline as above

Outcomes

Primary: time to first rescue dose and cumulative amount of rescue analgesic (tramadol 100 mg IV for VAS pain score > 4, up to 400 mg max)

Secondary: VAS pain scores at several time points up to 24 h, numbers of participants in each group requiring rescue medication within various postoperative intervals and cumulatively, adverse events, patient satisfaction at 24 h (0 = poor to 4 = excellent)

Source of funding

No funding

Were treatment groups comparable at baseline?

Yes

Details of preoperative pain

None – participants with history of usage of paracetamol, opioids, or NSAIDs for 3 months were excluded

Notes

Third group receiving paracetamol preemptively not included in this review. All participants received fentanyl 1 µg/kg at induction of anesthesia, which had a total duration of about 100 min in all groups.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not mentioned

Incomplete outcome data (attrition bias)
All outcomes

Low risk

It appears that all participants completed the study and contributed data for each outcome at all relevant time points

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

Unclear risk

50 to 199 participants per arm of the study (100 paracetamol, 100 placebo)

Atef 2008

Methods

Randomized, double‐blind, placebo‐controlled

Medications administered at the end of surgery

Participants

Type of surgery: elective standard bipolar diathermy tonsillectomy

Paracetamol group

Entered/completing: 38/38

Age (mean, SD): 27 ± 4

Sex (male, %): 50

Placebo group

Entered/completing: 38/38

Age (mean, SD): 25 ± 5

Sex (male, %): 47

Interventions

Intervention: paracetamol 1 g IV in 100 ml normal saline over 15 min

Placebo: 100 ml normal saline

Outcomes

Pain intensity at rest and on swallowing (VAS 0 to 100)

Pain relief (defined as a VAS score of < 30 mm at rest and < 50 mm on swallowing

Opioid consumption (pethidine)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes ‐ patient characteristics and duration of operation

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer randomization

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Nurse not involved in the study prepared the study solutions. Similar appearance of the study infusions assured blinding.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts; figures suggest that all participants reported data

Selective reporting (reporting bias)

Low risk

Primary outcome stated and fully reported. Stated secondary outcomes fully reported.

Size

High risk

Fewer than 50 participants per arm of the study (38 paracetamol, 38 placebo)

Aubrun 2003

Methods

Randomized, placebo‐controlled, double‐blind

Medications administered at the beginning of skin closure

Participants

Type of surgery: orthopedic, abdominal, general, or gynecological surgery

Propacetamol group

Entered/completing: ?/275

Age (mean, SD): 44 (range 18 to 85)

Sex (male, %): 46

Placebo group

Entered/completing: ?/275

Age (mean, SD): 45 (18 to 72)

Sex (male, %): 42

Interventions

Intervention: 2 g propacetamol over 15 min

Placebo: 125 ml saline

Outcomes

Morphine related AEs

Opioid consumption (morphine)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: patient characteristics, type and duration of surgery, expected postoperative pain, ASA status and type of anesthesia

Details of preoperative pain

Not mentioned, but anesthetists were asked to exclude patients who were expected to have no postoperative pain and those who were expected to have very severe postoperative pain requiring prolonged epidural and/or spinal postoperative analgesia or prolonged postoperative sedation and/or patient‐controlled analgesia (PCA).

Notes

Minor protocol violation occurred in 80 (15%) participants. There were no significant differences between the 2 groups.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomization was stratified according to centers

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Each vial was prepared immediately before administration by a nurse who was not involved in the care or pain assessment of the patient. Vials containing 2 g of propacetamol (yielding 1 g of acetaminophen) or saline were administered IV over 15 min.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3% of randomized participants were not included in analysis, but reasons for exclusion suggest outcome would be unaffected

Selective reporting (reporting bias)

Unclear risk

Primary outcome, morphine‐related adverse events, reported in full, except for incidence of bronchospasm. All secondary outcomes reported, but VAS and pain relief only reported as "no significant difference" between groups.

Size

Low risk

>/= 200 participants in each arm of the study

Beaussier 2005

Methods

Randomized, double‐blind, double‐dummy, active‐controlled

Medications administered at the beginning of wound closure

Participants

Type of surgery: inguinal hernia repair

Propacetamol group

Entered/completing: 90/90

Age (mean, SD): 46 ± 14

Sex (male, %): 94

Parecoxib group

Entered/completing: 92/90

Age (mean, SD): 42 ± 14

Sex (male, %): 91

Interventions

Intervention: 2 g propacetamol over 15 min

Control: parecoxib 40 mg IV

Outcomes

Primary: opioid consumption (morphine)

Pain intensity at rest and while coughing (VRS, VAS) and derived summary measures

Source of funding

Pfizer SA

Were treatment groups comparable at baseline?

Yes: intraoperative opioid consumption and time to tracheal extubation did not differ between groups; demographics (age, sex, weight, height) similar

Details of preoperative pain

Patients with chronic pain excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization performed centrally as blocks of 4 and with a 2:2 treatment ratio. In each center, treatment allocation was performed on the basis of one complete treatment block.

Allocation concealment (selection bias)

Low risk

Central allocation

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐dummy design employed. Propacetamol was administered by slow infusion over 15 min whereas parecoxib was injected by rapid bolus. Each participant received both an active product and the placebo of the other product.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

For primary outcome, data reported for both modified‐ITT population and per‐protocol population. Secondary outcomes reported data for ITT population.

Selective reporting (reporting bias)

Low risk

All outcomes reported with mean data or raw numbers

Size

Unclear risk

50 to 199 participants per arm of the study (90 propacetamol, 92 parecoxib)

Brodner 2011

Methods

Prospective, double‐blind, placebo‐ and active‐controlled study

Multiple‐dose study, first dose administered 30 min before the end of surgery. Outcomes assessed for at least 48 h and up to 1 week in patients not discharged.

Participants

Type of surgery: plastic surgery (breast surgery, inguinal or axillary dissections), oral and maxillofacial surgery (correction of retrognathism and prognathism), gynecological (laparoscopy, breast surgery), and urological (cystoscopy, transurethral prostatectomy) surgery and orthopedic surgery (hip endoprosthesis for coxarthrosis)

Paracetamol group

Entered/completing: 49/45

Age (mean, SD): 50.5 ± 17.5

Sex (male, %): 26.5%

Dipyrone group

Entered/completing: 49/41

Age (mean, SD): 45.5 ± 17.9

Sex (male, %): 44.9%

Parecoxib group

Entered/completing: 49/44

Age (mean, SD): 49.4 ± 14.6

Sex (male, %): 26.5%

Placebo group

Entered/completing: 49/45

Age (mean, SD): 42.8 ± 16.8

Sex (male, %): 49.0%

Interventions

Paracetamol 1 g/100 ml NS over 15 min every 6 h for at least 48 h

Dipyrone 1 g every 6 h, parecoxib 40 mg every 12 h (saline every 6 h between doses), or placebo (0.9% saline) every 6 h as above

Outcomes

Primary: dynamic VAS (0 to 100) for pain localized to the site of surgery

Secondary: time to first piritramide PCA bolus and piritramide consumption as quantified by the number of boluses demanded and administered; satisfaction rated as 1, excellent; 2, good; 3, moderate; 4, insufficient; and 5, poor; adverse events (respiratory depression, N/V, sedation, itching sweating)

Source of funding

Bristol‐Myers Squibb, Munich, Germany, and Pfizer Pharma GmbH, Karlsruhe, Germany

Were treatment groups comparable at baseline?

Yes, with 3 exceptions: participants of group 3 parecoxib had a significantly shorter duration of anesthesia and needed significantly less intraoperative sufentanil compared to group 4 placebo, and there were more women in group 1 paracetamol and group 3 parecoxib than in group 2 dipyrone and group 4 placebo

Details of preoperative pain

Surgical area (0 to 100 VAS): paracetamol 9.2 ± 17.1, dipyrone 10.8 ± 17.2, parecoxib 13.3 ± 16.6, placebo 6.0 ± 13.2

Notes

Numbers completing based on number of participants discontinued after at least 2 doses of intervention. ITT analysis employed – no participants lost to follow‐up at 42 h.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

“assigned by random numbers”

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Low risk

“All study drugs were prepared by the hospital pharmacy in identical glass bottles as infusions of 100 ml. The bottles were labelled with patient number and time of administration. Infusions were administered by a blinded attending physician”.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups. ITT analysis performed, but no mention of how missing data imputed.

Selective reporting (reporting bias)

Unclear risk

Secondary outcome, patient satisfaction, reported as mean across all groups and statement that all participants were satisfied with their pain treatment. No mean data for each group and no details of what point on scale was defined as satisfied.

Size

High risk

Fewer than 50 participants per arm of the study (49 paracetamol, 49 dipyrone, 49 parecoxib, 49 placebo)

Cakan 2008

Methods

Randomized, double‐blind, placebo‐controlled, over 24 h

Medications administered during skin closure

Participants

Type of surgery: elective lumbar laminectomy and discectomy

Paracetamol group

Entered/completing: 20/20

Age (mean, SD): 41 ± 10

Sex (male, %): 60

Placebo group

Entered/completing: 20/20

Age (mean, SD): 44 ± 10

Sex (male, %): 55

Interventions

Intervention: paracetamol 1 g IV over 15 min

Placebo: 100 ml normal saline

Outcomes

Pain intensity at rest or movement (VAS)

Opioid consumption (morphine)

All other outcomes reported at 24 h only

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographic data (sex, age, duration of surgery, intraoperative opioid use) and vital signs

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated block randomization

Allocation concealment (selection bias)

Low risk

Sealed, opaque envelopes

Blinding (performance bias and detection bias)
All outcomes

Low risk

Placebo administered in same solution over same time period

Incomplete outcome data (attrition bias)
All outcomes

Low risk

It appears that all participants completed the study and contributed data for each outcome at all relevant time points

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (20 paracetamol, 20 placebo)

Chen 2011

Methods

RCT, 60 participants were randomly divided into 2 groups, with 30 participants in each group

Participants in Group I were treated with 2 g propacetamol 15 min before the end of operation

Participants

Type of surgery: lumbar spine surgery

Propacetamol group

Entered/completing: 30

Age (mean, SD): 48, 13

Sex (male, %): 13, 43%

Control group

Entered/completing: 30

Age (mean, SD): 53, 14

Sex (male, %): 14, 47%

Interventions

2 g propacetamol in 100 ml saline, intravenous injection, 15 min before the end of operation

Placebo: 100 ml saline, intravenous injection, 15 min before the end of operation

Outcomes

The authors did not point out which were primary outcomes

Vomiting frequency in 48 h after the operation

VAS pain score (0 to 10), Ramsay sedation score(0, 1, 2, 3), breathing frequency, heart rate and mean arterial pressure were observed at the time of 0 min, 30 min, 1 h, 2 h, 4 h, 6 h, 12 h, 24 h, 36 h, 48 h after the operation

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: sex, age, weight, height

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No details reported

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not mentioned

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Reported as no incomplete outcome data in the study

Selective reporting (reporting bias)

High risk

There were only comparisons of VAS pain scores and Ramsay sedation scores between the 2 groups as shown in Table 2 and 3

Size

High risk

Fewer than 50 participants per arm of the study (30 propacetamol, 30 placebo)

Dejonckheere 2001

Methods

Randomized, blinded, active‐controlled

Medications administered on request in the PACU

Participants

Type of surgery: thyroidectomy

Propacetamol group

Entered/completing: 40/40

Age (mean, SD): 46.9 ± 2.1

Sex (male, %): 15

Tramadol group

Entered/completing: 40/40

Age (mean, SD): 44.1 ± 1.8

Sex (male, %): 10

Interventions

Intervention: 2 g IV propacetamol

Control: tramadol 1.5 mg/kg

Outcomes

Opioid consumption (morphine via PCA)

Pain intensity (VAS)

Source of funding

SearΙe Continental Pharma Ιnc provided the trial drugs and statistical assistance

Were treatment groups comparable at baseline?

Yes: demographics; duration of surgery and anesthesia; intraoperative opioid use; nausea, vomiting, and drowsiness incidence pre‐interventions

Details of preoperative pain

Not reported ‐ participants with chronic opioid use were excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

It appears that all participants completed the study and contributed data for each outcome at all relevant time points

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (40 propacetamol, 40 tramadol)

Delbos 1995

Methods

Randomized, double‐blind, placebo‐controlled

Medications administered in the recovery room

Participants

Type of surgery: knee ligamentoplasty

Propacetamol group

Entered/completing: 30/29

Age (mean, SD): 25.5 ± 5.6

Sex (male, %): 97

Placebo group

Entered/completing: 30/28

Age (mean, SD): 26.3 ± 5.8

Sex (male, %): 90

Interventions

Intervention: 2 g propacetamol in 125 ml 5% dextrose over 15 min

Placebo: 125 ml 5% dextrose

Outcomes

Opioid consumption (morphine via PCA)

Pain intensity (VAS 0 to 100 and 5‐point VRS) and derived summary measures

Global efficacy (5‐point VRS)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics, duration of surgery

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not described

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Data presented for some outcomes from all participants, but for other outcomes from only those apparently completing the study

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (30 propacetamol, 30 placebo)

Eremenko 2008

Methods

Randomized, blinded, placebo‐controlled

Medications administered 30 min before extubation

Participants

Type of surgery: coronary bypass surgery

Paracetamol group

Entered/completing: 22/?

Age (mean, SD): unclear

Sex (male, %): 77

Placebo group

Entered/completing: 23/?

Age (mean, SD): unclear

Sex (male, %): 73

Interventions

Intervention: paracetamol 1 g/100 ml IV (every 6 h x 4 doses)

Placebo: 100 ml normal saline

Outcomes

Inspiratory volume

Pain intensity (VRS)

AEs not reported

All other outcomes described over duration of study (18 h)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics

Details of preoperative pain

Not reported

Notes

Russian language study

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Described as blinded, but no mention of whether single‐ or double‐blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Not described

Selective reporting (reporting bias)

Unclear risk

Not described

Size

High risk

Fewer than 50 participants per arm of the study (22 paracetamol, 23 placebo)

Faiz 2014

Methods

Randomized, double‐blind, active‐controlled. Evaluated up to 24 h after surgery.

Medications administered prior to skin closure

Participants

Type of surgery: elective abdominal hysterectomy

Paracetamol group

Entered/completing: 40/40

Age (mean, SD): 49.9 ± 6.9

Sex (male, %): 0

Control group

Entered/completing: 40/40

Age (mean, SD): 47.2 ± 7.2

Sex (male, %): 0

Interventions

Paracetamol 15 mg/kg in 100 ml NS, single dose over 15 min

Ketamine 0.15 mg/kg administered as above

Outcomes

Primary: pain (VAS 0 to 10) in recovery room and at 4, 6, 12 and 24 h postop

Secondary: sedation (Ramsay scale), adverse events (nausea, vomiting, respiratory complications, hemodynamic changes), rescue analgesia (pethidine 15 mg for VAS pain > 3)

Source of funding

Iran University of Medical Sciences

Were treatment groups comparable at baseline?

Yes: demographics and duration of surgery

Details of preoperative pain

Not reported, but participants currently using opioids were excluded

Notes

Low dose of ketamine used in comparator group

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Block randomization

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Low risk

“Both medication solutions were prepared by the research pharmacist in 100 ml of normal saline and were administered by the anesthesia care team within a 15‐minute time period. The administering team was blinded to the nature of the infusate”.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts; tables suggest that all participants reported data

Selective reporting (reporting bias)

Low risk

All planned primary and secondary outcomes reported, although total amount of rescue analgesia not reported. Confirmed on trials registry (http://www.irct.ir/searchresult.php?id=11319&number=1).

Size

High risk

Fewer than 50 participants per arm of the study (40 paracetamol, 40 ketamine)

Farkas 1992

Methods

Randomized, double‐blind, double‐placebo, placebo‐ and active‐controlled

Medication administered when baseline pain reached at least moderate intensity

Participants

Type of surgery: abdominal aortic repair

Propacetamol group

Entered/completing: 29/15

Age (mean, SD): 64.3 ± 2.2

Sex (male, %): 3

Dipyrone group

Entered/completing: 30/21

Age (mean, SD): 62.4 ± 1.7

Sex (male, %): 20

Placebo group

Entered/completing: 30/15

Age (mean, SD): 64.3 ± 1.8

Sex (male, %): 3

Interventions

Intervention: 2 g propacetamol over 2 min

Control: 2.5 g dipyrone plus 0.01 g pitofenone IV

Placebo: not described

Outcomes

Pain intensity (5‐point VRS)

Requirement for rescue analgesia (morphine)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics, baseline postoperative pain score

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization table

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

"Investigator who did not know the nature of the products, infused the test products to each patient according to their number of entry into the trial. The patients were then monitored in the recovery room over six hours by the same investigator who did not know the nature of the product administered".

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Post‐rescue assessments imputed using LOCF; imbalance amongst groups in number of participants withdrawn due to requirement for rescue analgesia

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (29 propacetamol, 30 dipyrone, 30 placebo)

Fletcher 1997

Methods

Randomized, double‐blind, active‐ and placebo‐controlled

Medications administered at skin closure (and repeated every 6 h x 48 h)

Participants

Type of surgery: surgery of one herniated lumbar disc

Propacetamol group

Entered/completing: 15/14

Age (mean, SD): 41.8 ± 2.7

Sex (male, %): 53

Ketoprofen group

Entered/completing: 15/14

Age (mean, SD): 49.7 ± 2.9

Sex (male, %): 53

Placebo group

Entered/completing: 15/15

Age (mean, SD): 41.8 ± 2.4

Sex (male, %): 60

Interventions

Intervention: 2 g propacetamol in 125 ml dextrose 5%

Control: ketoprofen 50 mg

Control: combination of ketoprofen with propacetamol (not included in our analysis)

Placebo: 125 ml dextrose 5%

Outcomes

Pain intensity at rest and with movement (VAS)

Sedation (4‐point categorical scale)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics; preoperative pain; duration of surgery

Details of preoperative pain

Incidence of preoperative leg and/or back pain similar between groups. Mean severity of preoperative pain similar (ranged from 42 to 51/100) between groups.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Before the study began, a random number table was used to generate a randomized schedule specifying the group to which each patient would be assigned upon entry into the trial

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

All drugs were administered IV after dilution in 125 ml dextrose 5% labeled with the randomization number of the participant. Participants in all groups received 2 injections to assure blinding.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Low attrition rate balanced amongst groups

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (15 propacetamol, 15 ketoprofen, 15 placebo)

Hahn 2003

Methods

Randomized, double‐blinded, placebo‐controlled

Medications administered after surgery and immediately before extubation

Participants

Type of surgery: laparoscopic sterilization

Propacetamol group

Entered/completing: 15/15

Age (mean, SD): 36 ± 4

Sex (male, %): 0

Placebo group

Entered/completing: 16/16

Age (mean, SD): 37 ± 4

Sex (male, %): 0

Interventions

Intervention: 40 mg/kg propacetamol

Control: 20 mg/kg propacetamol (not included in our analysis)

Control: 10 mg/kg propacetamol (not included in our analysis)

1 g propacetamol was dissolved in 5 ml of contained solvent and administered as bolus

Placebo: normal saline

Outcomes

Opioid consumption (alfentanil via PCA)

Postoperative pain at rest and with movement (10 cm VAS)

Source of funding

SmithKline Beecham, Denmark supported the study. The infusion pumps were supplied by Baxter, Denmark.

Were treatment groups comparable at baseline?

Yes: demographics and duration of anesthesia

Details of preoperative pain

Patients were excluded if they had a history of chronic pain

Notes

40 mg/kg dose chosen in analysis as, based on participant weights, this would be closest dose to standard 2 g of propacetamol

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Blocked randomization

Allocation concealment (selection bias)

Low risk

Sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

Low risk

Drugs were administered by an anesthetist who had no further contact with the participant or study personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Minimal number of dropouts; it appears that all other data reported for remaining participants and at all relevant time points

Selective reporting (reporting bias)

Unclear risk

Time points not specified in Methods section for primary outcome; data pooled for different dosing regimens post 3 h

Size

High risk

Fewer than 50 participants per arm of the study (15 propacetamol, 16 placebo)

Hans 1993

Methods

Randomized, placebo‐controlled

Medications administered at end of surgery

Participants

Type of surgery: lumbar disc surgery

Propacetamol group

Entered/completing: 20/20

Age (mean, SD): 38.3 ± 9.4

Sex (male, %): 80

Placebo group

Entered/completing: 20/20

Age (mean, SD): 38.2 ± 10.8

Sex (male, %): 55

Interventions

Intervention: propacetamol 2 g over 20 min

Placebo: saline

Outcomes

Opioid consumption (piritramide on request)

Pain intensity (VAS)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics and duration of surgery

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

It appears that all participants completed the study and contributed data for each outcome at all relevant time points

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (20 propacetamol, 20 placebo)

Hiller 2004

Methods

Randomized, double‐blind, active‐controlled

Medications administered immediately after induction of anesthesia (surgeries averaged around 30 min)

Participants

Type of surgery: elective tonsillectomy

Propacetamol group

Entered/completing: 26/25

Age (mean, SD): 29 ± 11

Sex (male, %): 52

Diclofenac group

Entered/completing: 25/25

Age (mean, SD): 27 ± 7

Sex (male, %): 44

Interventions

Intervention: 2 g propacetamol in 100 ml normal saline

Control: 75 mg diclofenac

Control: 2 g propacetamol plus 75 mg diclofenac (not included in our analysis)

Outcomes

Opioid consumption (oxycodone)

Pain intensity at rest and on swallowing (VRS, VAS)

Patient satisfaction (VAS)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics; duration of surgery, intraoperative opioid use; blood loss

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Low risk

Sealed envelope method

Blinding (performance bias and detection bias)
All outcomes

Low risk

Nurse preparing solutions did not participate in the study. To maintain double‐blind design volumes infused were equal.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Various reasons for dropouts amongst groups, data analyzed in completers only, but minimal missing data

Selective reporting (reporting bias)

Unclear risk

Outcomes not specified in Methods section; possibility of additional post‐hoc analyses cannot be ruled out

Size

High risk

Fewer than 50 participants per arm of the study (26 propacetamol, 25 diclofenac)

Hiller 2012

Methods

Randomized, double‐blind, placebo‐controlled, over 24 h

Medications administered during skin closure

Participants

Type of surgery: major spine (posterior and/or anterior correction)

Paracetamol group

Entered/completing: 18/18

Age (mean, SD): 15.1 ± 2.0

Sex (male, %): 5, 27.8%

Placebo group

Entered/completing: 18/18

Age (mean, SD): 14.4 ± 1.9

Sex (male, %): 6, 33.3%

Interventions

Paracetamol 30 mg/kg IV (3 ml/kg) over 15 min, max dose 1.5 g, q8h x 3 doses

Placebo (NS) as above

Outcomes

Primary: pain scores at rest on the surgical ward q1h for 24 h as the highest VAS 0 to 10 score during the preceding hour

Secondary: time to first and total PCA oxycodone dose; supplemental analgesia (for VAS ≥ 6 oxycodone 0.05 mg/kg IV, if VAS score still ≥ 6, parecoxib 20 to 40 mg IV); adverse events (nausea, vomiting, and pruritus); sedation (Michigan sedation scale: 0, awake; 4, unresponsive to painful stimulus); plasma levels of acetaminophen and metabolites

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics; duration of surgery and anesthesia; intraoperative analgesia; blood loss; spinal pathology and type of procedure

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random list

Allocation concealment (selection bias)

Low risk

Sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

Low risk

“An unblinded anesthesia nurse who did not participate in peri‐ or postoperative care opened an envelope and prepared the study medications (acetaminophen or placebo)”.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

ITT analysis (method of imputation not specified); reasons for protocol violations specified and similar between groups, and results reported to be similar if these participants were excluded.

Selective reporting (reporting bias)

High risk

All outcomes from Methods section reported in Results section (other than number of participants with pruritus), but many only presented graphically and without SDs

Size

High risk

Fewer than 50 participants per arm of the study (18 paracetamol, 18 placebo)

Hynes 2006

Methods

Randomized, double‐blinded, double‐dummy, placebo‐ and active‐controlled

Medication administered on postoperative day 1, when baseline pain reached moderate‐to‐severe intensity

Participants

Type of surgery: total hip arthroplasty

Propacetamol group

Entered/completing: 40/40

Age (mean, SD): 65.7 ± 9.8

Sex (male, %): 40

Diclofenac group

Entered/completing: 40/40

Age (mean, SD): 65.6 ± 7.6

Sex (male, %): 55

Placebo group

Entered/completing: 40/40

Age (mean, SD): 66.1 ± 7.1

Sex (male, %): 45

Interventions

Intervention: 2 g propacetamol IV

Control: 75 mg diclofenac IM

Placebo: double‐dummy not described

Outcomes

Pain intensity (VRS, VAS)

Pain relief (categorical)

Time to request for rescue medication

Global assessment (categorical)

Source of funding

Supported by Bristοl‐Myers Squibb

Were treatment groups comparable at baseline?

Yes: demographics; duration of anesthesia; baseline postoperative pain

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomization

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐dummy technique employed

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

11/40 missing pain assessment data at 5 h in intervention group due to lack of efficacy and administration of rescue dose (29/40 in placebo group), but all 40 included in efficacy analysis. Data were imputed using LOCF.

Selective reporting (reporting bias)

Unclear risk

All outcomes from Methods section reported in Results section, but time to rescue was instead reported as number of participants requesting rescue

Size

High risk

Fewer than 50 participants per arm of the study (40 propacetamol, 40 diclofenac, 40 placebo)

Inal 2006

Methods

Parallel, active‐controlled, randomized, double‐blind, single dose over 24 h

Participants

Type of surgery: cesarean section

Paracetamol group

Entered/completing: 25/unclear

Age (mean, SD): 30.6 ± 4.23

Sex (male, %): 0

Pethidine group

Entered/completing: 25/unclear

Age (mean, SD): 29.6 ± 3.51

Sex (male, %): 0

Interventions

Paracetamol 1 g/100 ml single dose over 15 min, 30 min before end of surgery

pethidine 100 mg IV as above

Outcomes

Primary: VAS pain intensity at 0, 1, 5, 30 min and 1, 2, 4, 6, 8 and 24 h after surgery

Secondary:

Side effects

Total rescue analgesic use (unspecified) over 24 h for pain > 7/10

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: age, height, weight, duration of surgery, duration of anesthesia

Details of preoperative pain

Participants with chronic abdominal pain were excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No details reported

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

No details reported

Incomplete outcome data (attrition bias)
All outcomes

High risk

Unclear how many participants completed the study; mean pain data did not have SDs; 24 h rescue analgesic use did not specify analgesic administered

Selective reporting (reporting bias)

Low risk

All outcomes in Methods section were reported in Results

Size

High risk

Fewer than 50 participants per arm of the study (25 paracetamol, 25 pethidine)

Jahr 2012 Study 2, 65+

Methods

Randomized, double‐blind, placebo‐controlled single dose study evaluated 6 h postop

Study entry occurred the day after surgery

Participants

Type of surgery: orthopedic (THA)

Paracetamol group

Entered/completing: 16/16

Age (mean, SD): 74.6 (5.7)

Sex (male, %): 8 (50%)

Placebo

Entered/completing: 17/17

Age (mean, SD): 73.9 (6.2)

Sex (male, %): 5 (29.4%)

Interventions

Paracetamol: 1000 mg IV as a single dose

Placebo

Each arm had free access to PCA (details not specified including if it could be different opioids in PCA)

Outcomes

Primary: pain relief, pain intensity, total rescue medication, median time to rescue, SPID6

Secondary: adverse events

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes: age, sex, weight, height, ASA classification, baseline PI

Details of preoperative pain

Not reported

Notes

Study terminated early due to an issue unrelated to efficacy or safety of the interventions. Precipitates were found in the placebo vials. Participants were required to have moderate pain the day after surgery. Baseline PI scores were not statistically different between groups (VAS 0 to 100). Details regarding drugs used/dosing of opioid PCA for all participants are lacking. (“…each arm having free access to PCA opioids.”)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not described; reported as double‐blind

Incomplete outcome data (attrition bias)
All outcomes

Low risk

ITT analysis:

WOCF if a participant was given rescue medication within the first 4 h after dosing

LOCF if a participant missed the 4‐hour mean PI assessment and had not received rescue medication or if a participant terminated the study due to an adverse event

Extrapolation if a participant missed one mean PI assessment and no rescue medication was received

Selective reporting (reporting bias)

Unclear risk

Reported all outcomes but no data presented for pain relief

Size

High risk

Fewer than 50 participants per arm of the study (16 paracetamol, 17 placebo)

Jahr 2012 Study 2, 65‐

Methods

Randomized, double‐blind, placebo‐controlled, single dose study evaluated 6 h postop

Study entry occurred the day after surgery.

Participants

Type of surgery: orthopedic (THA)

Paracetamol group

Entered/completing: 19/19

Age (mean, SD): 52.6 (7.9)

Sex (male, %): 9 (47.4%)

Placebo

Entered/completing: 17/17

Age (mean, SD): < 65: 57.2 (6.4)

Sex (male, %): 8 (47.1%)

Interventions

Paracetamol: 1000 mg IV as a single dose

Placebo

Each arm had free access to PCA (details not specified including if it could be different opioids in PCA)

Outcomes

Primary: pain relief, pain intensity, total rescue medication, median time to rescue, SPID6

Secondary: adverse events

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes: age, sex, weight, height, ASA classification, baseline PI

Details of preoperative pain

Not reported

Notes

Study terminated early due to an issue unrelated to efficacy or safety of the interventions. Precipitates were found in the placebo vials. Participants were required to have moderate pain the day after surgery. Baseline PI scores were not statistically different between groups (VAS 0 to 10). Details regarding drugs used/dosing of opioid PCA for all participants are lacking. (“…each arm having free access to PCA opioids.”)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not described; reported as double‐blind

Incomplete outcome data (attrition bias)
All outcomes

Low risk

ITT analysis:

WOCF if a participant was given rescue medication within the first 4 h after dosing

LOCF if a participant missed the 4‐hour mean PI assessment and had not received rescue medication or if a participant terminated the study due to an adverse event

Extrapolation if a participant missed one mean PI assessment and no rescue medication was received

Selective reporting (reporting bias)

Unclear risk

Reported all outcomes but no data presented for pain relief

Size

High risk

Fewer than 50 participants per arm of the study (19 paracetamol, 17 placebo)

Jahr 2012 Study 3, 65+

Methods

Randomized, double‐blind, placebo‐controlled, multicenter repeated dose study evaluated up to 16 h postop

Study entry occurred the day after surgery. Participants were required to have moderate postop pain for eligibility

Participants

Type of surgery: orthopedic (THA)

Paracetamol group

Entered/completing: 15/15

Age (mean, SD): 71.4 +/‐ 4.7

Sex (male, %): 9 (60%)

Placebo

Entered/completing: 12/12

Age (mean, SD): 68.4 +/‐ 3.5

Sex (male, %): 6 (50%)

Interventions

Paracetamol: 1000 mg IV administered at 0, 4, 10, 16 h

Placebo

Outcomes

Primary: pain relief, pain intensity, total rescue medication, median time to rescue, SPID4, patient satisfaction

Secondary: adverse events

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes: age, sex, weight, height, ASA classification, baseline PI

Details of preoperative pain

Not reported

Notes

Only published as an abstract. Study terminated early due to an issue unrelated to efficacy or safety of the interventions. Precipitates were found in the placebo vials.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not described; reported as double‐blind

Incomplete outcome data (attrition bias)
All outcomes

Low risk

ITT analysis:

WOCF if a participant was given rescue medication within the first 4 h after dosing

LOCF if a participant missed the 4‐hour mean PI assessment and had not received rescue medication or if a participant terminated the study due to an adverse event

Extrapolation if a participant missed one mean PI assessment and no rescue medication was received

Selective reporting (reporting bias)

Unclear risk

Reported all outcomes but no data presented for pain relief

Size

High risk

Fewer than 50 participants per arm of the study (15 paracetamol, 12 placebo)

Jahr 2012 Study 3, 65‐

Methods

Randomized, double‐blind, placebo‐controlled, multicenter repeated dose study evaluated up to 16 h postop

Study entry occurred the day after surgery. Participants were required to have moderate postop pain for eligibility.

Participants

Type of surgery: orthopedic (THA)

Paracetamol group

Entered/completing: 15/unclear

Age (mean, SD): 54.1 +/‐ 6.2

Sex (male, %): 11 (73.3%)

Placebo

Entered/completing: 19/unclear

Age (mean, SD): 53.4 +/‐ 9.3

Sex (male, %): 14 (73.7%)

Interventions

Paracetamol: 1000 mg IV administered at 0, 4, 10, 16 h

Placebo

Outcomes

Primary: pain relief, pain intensity, total rescue medication, median time to rescue, SPID4, patient satisfaction

Secondary: adverse events

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes: age, sex, weight, height, ASA classification, baseline PI

Details of preoperative pain

Not reported

Notes

Only published as an abstract. Study terminated early due to an issue unrelated to efficacy or safety of the interventions. Precipitates were found in the placebo vials.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Not described; reported as double‐blind

Incomplete outcome data (attrition bias)
All outcomes

Low risk

ITT analysis:

WOCF if a participant was given rescue medication within the first 4 h after dosing

LOCF if a participant missed the 4‐hour mean PI assessment and had not received rescue medication or if a participant terminated the study due to an adverse event

Extrapolation if a participant missed one mean PI assessment and no rescue medication was received

Selective reporting (reporting bias)

Unclear risk

Reported all outcomes but no data presented for pain relief

Size

High risk

Fewer than 50 participants per arm of the study (15 paracetamol, 19 placebo)

Jarde 1997

Methods

Randomized, double‐blind, placebo‐ and active‐controlled

Medication administered immediately after surgery in patients with at least moderate pain

Participants

Type of surgery: hallux valgus

Propacetamol group

Entered/completing: 108/108

Age (mean, SD): 52.2 ± 13.0

Sex (male, %): 11

Placebo group

Entered/completing: 109/109

Age (mean, SD): 51.9 ± 13.6

Sex (male, %): 8

Interventions

Intervention: propacetamol 2 g in 125 ml dextrose 5% over 15 min

Control: oral paracetamol 1 g (not included in our analysis)

Placebo: 125 ml dextrose 5% and tablet

Outcomes

Pain intensity (categorical) and derived pain intensity difference, SPID and maximum pain intensity difference

Time to rescue medication

Global evaluation (categorical)

Source of funding

Supported by UPSA Laboratories

Were treatment groups comparable at baseline?

Yes: demographics; duration of surgery; baseline postoperative pain

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Inadequately described

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Participants requesting rescue medication had LOCF in efficacy analysis

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

Unclear risk

50 to 199 participants per arm of the study (108 propacetamol, 109 placebo)

Juhl 2006

Methods

Randomized, double‐blind, double‐dummy, active‐ and placebo‐controlled

Medication administered when baseline pain reached moderate‐to‐severe intensity within 6 h of surgery

Participants

Type of surgery: third molar extraction

Paracetamol group

Entered/completing: 132/132

Age (mean, SD): 25.0 ± 2.6

Sex (male, %): 41

Placebo group

Entered/completing: 33/33

Age (mean, SD): 25.2 ± 2.8

Sex (male, %): 55

Interventions

Intervention: IV paracetamol 1 g

Control: IV paracetamol 2 g (not included in our analysis)

Placebo: 100 ml solution

All interventions administered in 100 ml solution for each 1 g of paracetamol (or placebo) over 15 min

Outcomes

Pain relief (VAS and VRS) and derived TOTPAR

Pain intensity (VAS and VRS)

Time to request of rescue medication

Global evaluation (categorical)

Source of funding

Supported by Bristol‐Myers Squibb Company

Were treatment groups comparable at baseline?

Yes: demographics; ASA classification; number of teeth removed; baseline postoperative pain intensity; surgical trauma

No: longer duration of surgery in the IV paracetamol 1 g group in comparison with the IV paracetamol 2 g and placebo groups

Details of preoperative pain

Participants with other painful physical conditions that might confound pain assessment were excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Block randomization 4:4:1, each block n = 9

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

A double‐dummy method was used to assure double‐blinding

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

ITT analysis using LOCF. Unclear how many participants had data imputed.

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section, but SPID was only calculated using categorical pain intensity despite being measured with both categorical and VAS scales

Size

Unclear risk

50 to 199 participants per arm of the study (132 paracetamol, 33 placebo)

Kamath 2014

Methods

Randomized, parallel, active‐controlled trial; multiple doses evaluated for 24 h

Participants

Type of surgery: cesarean sections and gynecological surgeries

Paracetamol group

Entered/completing: 51/50

Age (mean, SD): not reported

Sex (male, %): 100% female

Butorphanol group

Entered/completing: 50/50

Age (mean, SD): not reported

Sex (male, %): 100% female

Interventions

Paracetamol: 1 g IV every 8 h

Butorphanol 2 mg IV every 12 h

Outcomes

Primary: pain intensity

Secondary: administration of rescue medication (tramadol), timing of rescue medication, adverse effects

Source of funding

ICMR under STS program

Were treatment groups comparable at baseline?

Not reported

Details of preoperative pain

Not reported

Notes

Poster presentation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

High risk

Not described; due to the fact that the study was likely unblinded we categorized this as high risk also

Blinding (performance bias and detection bias)
All outcomes

High risk

Not described; assume to be unblinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

One participant was not accounted for in the presentation of graphical results

Selective reporting (reporting bias)

Unclear risk

Timing of rescue medication was not presented in Results. No data for pain scores reported.

Size

Unclear risk

50 to 199 participants per arm of the study (51 paracetamol, 50 placebo)

Kampe 2006

Methods

Randomized, double‐blind, active‐controlled

Medications administered 30 min before the end of surgery

Participants

Type of surgery: breast cancer (breast conserving or total mastectomy, balanced between groups)

Propacetamol group

Entered/completing: 20/20

Age (mean, SD): 52 ± 10.2

Sex (male, %): 0

Dipyrone group

Entered/completing: 20/20

Age (mean, SD): 55.9 ± 8.7

Sex (male, %): 0

Interventions

Intervention: 1 g propacetamol in 100 ml solution over 15 min

Control: 1 g dipyrone

Outcomes

Pain intensity at rest and on coughing (VAS)

Opioid consumption (piritramide via PCA)

Patient satisfaction (categorical)

Source of funding

In part supported by a grant from BristoΙ‐Myers Squibb GmbFΙ, München, Germany, with publication support provided by the Department of Anaesthesiology, University of Cologne

Were treatment groups comparable at baseline?

Yes: demographics, type of procedure

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomization was based on a computer‐generated code

Allocation concealment (selection bias)

Low risk

Randomization results were sealed in sequentially numbered, opaque envelopes

Blinding (performance bias and detection bias)
All outcomes

Low risk

The infusions were made to look identical; participants and investigators were blinded to the study treatment

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"The data for all patients were eligible for statistical analysis."

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (20 propacetamol, 20 dipyrone)

Kara 2010

Methods

Randomized, active‐controlled study, multiple dose, evaluated up to 2 days postop

Medication administered at the end of the operation, without being contingent upon pain intensity

Rescue medication (meperidine/pethidine 1 mg/kg IM) given to both groups as rescue medication for VAS > 4

Participants

Type of surgery: trans‐urethral resection of prostate

Paracetamol group

Entered/completing: 25/25

Age (mean, SD): only median age reported (64.3)

Sex (male, %): 25 (100%)

Diclofenac group

Entered/completing: 25/25

Age (mean, SD): only median reported (66.8)

Sex (male, %): 25 (100%)

Interventions

Paracetamol 1 g/100 ml IV over 15 min twice daily

Diclofenac IM 75 mg at the end of the operation, followed by 75 mg IM for 24 h. Time interval between first two 75 mg doses not reported, but the authors describe this regimen as 150 mg once per day = 150 mg per 24 h.

Outcomes

Primary: pain intensity (VAS)

Secondary: hemoglobin levels, hemostatic variables (bleeding time PT, INR), adverse effects, rescue opioid use (pethidine)

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes: demographics; duration of surgery; transrectal ultrasound volume

Details of preoperative pain

Similar at baseline

Notes

No statistically/clinically significant differences in postoperative hemoglobin, hemostatic parameters or bleeding events between placebo, paracetamol, and diclofenac groups. Diclofenac dosing (2 x 75 mg given in presumably quick succession, then repeated as a 150 mg dose 24 h later) is highly idiosyncratic, high. This regimen could bias results towards a greater diclofenac effect in the first portion of the 24 h dosing interval, and a lesser effect towards the end, compared with a more conventional dosing regimen of 75 mg IM every 12 h.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

High risk

Not described. Assessed as high risk based on assumption of non‐blinding.

Blinding (performance bias and detection bias)
All outcomes

High risk

Not described; assume to be unblinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts or protocol violations

Selective reporting (reporting bias)

Unclear risk

All outcomes from Methods section reported in Results section; opioid use reported in Results but not specifically mentioned in Methods. No SD reported for VAS data.

Size

High risk

Fewer than 50 participants per arm of the study (25 paracetamol, 25 diclofenac)

Karaman 2010

Methods

Randomized, double‐blind, active‐controlled study, multiple dose, 24 h

Medication was administered at the end of surgery after skin closure

Participants

Type of surgery: ENT surgery (nasal/sinus, otologic, head/neck)

Paracetamol group

Entered/completing: 30/30

Age (mean, SD): 48.5 +/‐ 12.1

Sex (male, %): 16 (53%)

Dexketoprofen

Entered/completing: 30/30

Age (mean, SD): 54.8 +/‐ 8.6

Sex (male, %): 16 (53%)

Interventions

Paracetamol: 1 g IV at the end of surgery then at 6, 12, 18 h (4 g total)

Dexketoprofen: 50 mg IV at the end of surgery then repeated twice at an 8‐h interval (150 mg total)

Metamizol: 1 g IV at the end of surgery then repeated twice at an 8‐h interval (3 g total, not included in our analysis)

Outcomes

Primary: VAS (0 to 10) and VRS (0 to 3) pain intensity

Secondary: adverse events, sedation score, use of rescue medication (pethidine 1 mg/kg for VAS ≥ 30 mm)

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes: demographics; duration of surgery

Details of preoperative pain

Not reported ‐ participants were excluded if they had received analgesics within 12 h before surgery

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Participants and anesthetists were unaware of treatment assignments. All outcome measurements were recorded by the same anesthesia resident who was blinded to assignments. “All medicines were prepared by a nurse who had no other involvement in the study”

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts or protocol violations – complete data set obtained for all groups

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section although no data provided for sedation assessment

Size

High risk

Fewer than 50 participants per arm of the study (30 paracetamol, 30 dexketoprofen)

Kemppainen 2006

Methods

Randomized, double‐blind, placebo‐controlled

Medications administered at completion of surgery over 15 min

Participants

Type of surgery: endoscopic sinus

Paracetamol group

Entered/completing: 36/36

Age (mean, SD): not reported

Sex (male, %): not reported

Placebo group

Entered/completing: 38/38

Age (mean, SD): not reported

Sex (male, %): not reported

Interventions

Intervention: paracetamol 1 g IV

Placebo: 100 ml normal saline

Outcomes

Pain intensity (NRS)

Time to rescue medication

Opioid consumption (oxycodone)

Source of funding

Not reported

Were treatment groups comparable at baseline?

No details

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomization

Allocation concealment (selection bias)

Low risk

Opaque envelope method

Blinding (performance bias and detection bias)
All outcomes

Low risk

The nurse preparing the infusions did not participate in the study. Preparation of infusions of identical volumes (100 ml) to assure blinding.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"All the patients asked agreed to participate and there were no dropouts during the study".

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (36 paracetamol, 38 placebo)

Khajavi 2007

Methods

Randomized, double‐blind, active‐controlled

Medications administered directly before skin closure

Participants

Type of surgery: renal transplant

Paracetamol group

Entered/completing: 15/15

Age (mean, SD): 40.47 ± 11.2

Sex (male, %): 53

Morphine group

Entered/completing: 15/15

Age (mean, SD): 40.2 ± 11.6

Sex (male, %): 60

Interventions

Intervention: propacetamol 2 g IV over 10 min

Control: morphine 5 mg IV

Outcomes

Pain intensity (VRS)

Pain relief (VRS)

Source of funding

Not reported

Were treatment groups comparable at baseline?

No statistical analysis, but groups appear balanced for demographics

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Anesthesiologist blinded to the drug administered assessed pain score, blood pressure, heart rate, lab tests, etc. No description of blinding.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Table suggests that all participants (15 in each group) reported data at all time points

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (15 paracetamol, 15 morphine)

Khalili 2013

Methods

Randomized, double‐blind placebo‐controlled, single dose, over 24 h

IV acetaminophen was administered before skin closure versus a control group that received normal saline as placebo; preemptive group receiving 15 mg/kg 0.5 h preoperatively, not reported here

Participants

Type of surgery: orthopedic, lower extremity

Paracetamol group

Entered/completing: 25/25

Age (mean, SD): 36.8 +/‐ 14.8

Sex (male, %): 21 (84%)

Placebo group

Entered/completing: 25/25

Age (mean, SD): 37.8 +/‐ 12.9

Sex (male, %): 17 (68%)

Interventions

Paracetamol: 15 mg/kg in 100 ml of IV normal saline prior to skin closure

Placebo (normal saline) 100 ml prior to skin closure

Outcomes

Primary: pain intensity according to VRS

Secondary:

Timing, # participants requesting and dose of rescue medication (pethidine)

Adverse effects (sedation, hypotension, etc.)

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes: demographics; duration of surgery; site of surgery; postoperative VRS scores

Details of preoperative pain

Patients with a history of opioid use in the past 48 h or chronic pain were excluded; baseline pain scores not significantly different

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computerized (random number generator)

Allocation concealment (selection bias)

Low risk

Opaque envelopes

Blinding (performance bias and detection bias)
All outcomes

Low risk

Participants and anesthesiologists were blinded by “creating treatments that looked identical”

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts or protocol violations – complete data set obtained for both groups

Selective reporting (reporting bias)

High risk

Not all outcomes from Methods section reported in Results section (e.g., sedation scores, patient satisfaction)

Size

High risk

Fewer than 50 participants per arm of the study (25 paracetamol, 25 placebo)

Khan 2007

Methods

Parallel, single dose, active comparator, quasi‐randomized, double‐blinded over 4 h

Dose administered just before reversal of general anesthesia

Participants

Type of surgery: diagnostic knee arthroscopic procedures

Paracetamol group

Entered/completing: 43/unclear (appears to be 43 from Figures)

Age (mean, SD): range (entire population) 18 to 69 years

Sex (male, %): 90% (entire population)

Morphine group

Entered/completing: 41/unclear (appears to be 41 from Figures)

Age (mean, SD): see above

Sex (male, %): see above

Interventions

Paracetamol 1 g IV over 15 min

Morphine 0.1 mg/kg IV bolus

Outcomes

Primary: VRS pain intensity at 0, 1, 2, 3, and 4 h

Secondary: adverse effects

Source of funding

Not reported

Were treatment groups comparable at baseline?

No data presented

Details of preoperative pain

Not reported

Notes

Both interventions given along with 0.5% bupivacaine 20 ml intra‐articular injection

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

High risk

Randomization via last number of medical record number, with odd receiving paracetamol and even receiving morphine

Allocation concealment (selection bias)

High risk

As above

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Study mentioned once it was double‐blinded without further description

Incomplete outcome data (attrition bias)
All outcomes

High risk

No SDs for pain scores, unclear how many participants completed study

Selective reporting (reporting bias)

Low risk

All outcomes in Methods section reported in Results

Size

High risk

Fewer than 50 participants per arm of the study (43 paracetamol, 41 morphine)

Kilicaslan 2010

Methods

Paracetamol

Randomized, placebo‐controlled, multiple dose study evaluated 24 h postop

Medication was administered 15 min before the end of surgery

Participants

Type of surgery: cesarean section

Paracetamol group

Entered/completing: 25/25

Age (mean, SD): 28.8 +/‐ 4.8

Sex (male, %): 0 (100% female)

Placebo

Entered/completing: 25/25

Age (mean, SD): 27.6 +/‐ 5.4

Sex (male, %): 0 (100% female)

Interventions

Paracetamol: 1 g in 100 ml 15 min before the end of surgery and every 6 h x 24 h

Placebo: saline 100 ml 15 min before the end of surgery and every 6 h x 24 h

All participants received IV PCA (tramadol) – 20 mg bolus; 10 min lockout

Outcomes

Primary: pain score (VAS 0 to 10), tramadol consumption

Secondary: sedation scores, nausea/vomiting scores, adverse effects

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes: demographics; duration of surgery and anesthesia; weeks pregnant

Details of preoperative pain

Participants with chronic pain were excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Low risk

Sealed envelopes used

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Anaesthesiologists and participants were blinded. No other description provided.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Complete data provided for all participants. No one was excluded from the study.

Selective reporting (reporting bias)

Low risk

All outcomes reported in Methods are discussed in Results

Size

High risk

Fewer than 50 participants per arm of the study (25 paracetamol, 25 placebo)

Koppert 2006

Methods

Randomized, double‐blind, controlled, multiple dose study; evaluated outcomes over at least 3 days. Medication was administered immediately after surgery upon arrival in the PACU.

Participants

Type of surgery: hip replacement or surgery of the femoral shaft

Paracetamol group

Entered/completing: 27/25

Age (mean, SD): 76.7 +/‐ 8.9

Sex (male, %): 15 (55.6%)

Parecoxib group

Entered/completing: 28/25

Age (mean, SD): 76 +/‐ 8

Sex (male, %): 11 (39.3%)

Placebo group (saline)

Entered/completing: 28/25

Age (mean, SD): 76.7 +/‐ 8.6

Sex (male, %): 12 (42.9%)

Interventions

Paracetamol: IV infusion of 1000 mg paracetamol (Perfalgan) over 10 min; admin at 6‐h intervals for at least 3 days

Parecoxib: 40 mg IV over 10 min (Dynastat); admin at 12‐h intervals for at least 3 days

Placebo: saline IV over 10 min

Outcomes

Primary: renal function: blood samples (serum Cystatin C, creatinine, blood urea nitrogen, liver biochemistry); urine samples (creatinine clearance, urinary excretion of sodium, potassium, albumin, alpha1‐microglobulin; fluid balance (CVP)

Secondary: pain intensity (NRS 0 to 10), rescue medication usage including morphine equianalgesic dosages

Source of funding

Supported by Bristol‐Meyers Squibb

Were treatment groups comparable at baseline?

“All groups were comparable with regard to age, weight, height, distribution of sex, preexisting diseases, and ASA status…. Type and lengths of surgical and anesthetic procedures across the treatment groups were similar… Furthermore, consumption of crystalloids and colloids were similar.”

Details of preoperative pain

Not reported

Notes

“If a patient had received NSAIDs or COX‐2 inhibitors, there was a washout period of at least 72 h and the weak opioid, tramadol, was provided as a substitute.”

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“Randomization of the study medication (parecoxib versus paracetamol versus saline) was performed by computer‐generated codes maintained in sequentially numbered, opaque envelopes. Additional envelopes were provided if participants had to be excluded after recruitment and randomization.”

Allocation concealment (selection bias)

High risk

Despite use of sequentially numbered envelopes, participants and nursing staff on ward were unblinded

Blinding (performance bias and detection bias)
All outcomes

High risk

Anesthesiologist, nursing staff, and investigators were blinded. All study medication solutions were prepared by a hospital pharmacist who was not involved in the data collection. On the ward, participants and nursing staff were unblinded. How blinding was maintained was not described.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No missing outcome data. All participants that did not complete the study were accounted for.

Selective reporting (reporting bias)

Low risk

All outcomes were reported in Results

Size

High risk

Fewer than 50 participants per arm of the study (27 paracetamol, 28 parecoxib, 28 placebo)

Korkmaz 2010

Methods

Randomized, double‐blind, active‐ and placebo‐controlled, multiple dose, 24 h

Medications administered at time of wound closure

Participants

Type of surgery: lumbar disc

Paracetamol group

Entered/completing: 20/20

Age (mean, SD): 46.0 ± 11.0

Sex (male, %): 11, 55%

Lornoxicam group

Entered/completing: 20/20

Age (mean, SD): 46.7 ± 12.8

Sex (male, %): 12, 60%

Placebo group

Entered/completing: 20/19

Age (mean, SD): 44.5 ± 14.4

Sex (male, %): 9, 47.4%

Interventions

Paracetamol 1 g in 100 ml NS over 15 min every 6 h

Metamizole 1 g (not included in our analysis), lornoxicam 8 mg or saline. All administered as above (lornoxicam every 12 h).

Placebo: normal saline 100 ml infused over 15 min every 6 h

Outcomes

Primary: VAS (0 to 10) pain intensity over 24 h

Secondary: sedation (Ramsay score); morphine consumption via PCA, other adverse events, vital signs

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics; smoking status; history of postoperative nausea and vomiting; duration of anesthesia; type of surgery; number of herniated discs; experience of surgeon

Details of preoperative pain

Not reported

Notes

All participants received morphine PCA 100 mg in 100 ml normal saline for 24 h postop (1 mg bolus, lockout 7 min)

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Method not described

Allocation concealment (selection bias)

Low risk

Opaque envelopes

Blinding (performance bias and detection bias)
All outcomes

Low risk

“The study solutions were prepared by a nurse, whereas postoperative data were collected by a blinded anaesthesiologist. The colour of lornoxicam solution is yellow; to maintain blinding, all solutions were covered by aluminium foil during administration”.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Per‐protocol analysis only, but number of dropouts small and apparently unrelated to interventions

Selective reporting (reporting bias)

High risk

Adverse events only reported as similar between groups, with no accompanying data. Morphine requirements were reported in Results and not specifically mentioned in Methods. Blood pressure, heart rate, and sedation not reported in Results.

Size

High risk

Fewer than 50 participants per arm of the study (20 paracetamol, 20 lornoxicam, 20 placebo)

Lahtinen 2002

Methods

Randomized, double‐blinded, placebo‐controlled

Medications administered immediately after arrival in the PACU

Participants

Type of surgery: cardiac

Propacetamol group

Entered/completing: unclear/40

Age (mean, SD): 59 ± 6

Sex (male, %): 85

Placebo group

Entered/completing: unclear/39

Age (mean, SD): 58 ± 7

Sex (male, %): 90

Interventions

Intervention: 2 g propacetamol in 100 ml normal saline

Placebo: 100 ml normal saline

Outcomes

Opioid consumption (oxycodone via PCA and rescue)

Pain intensity at rest and during deep breath (VAS)

Patient satisfaction (categorical)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics; duration of anesthesia and surgery; intraoperative opioid use

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random numbers and a balanced design with a computer program

Allocation concealment (selection bias)

Low risk

Randomization/blinding performed in pharmacy

Blinding (performance bias and detection bias)
All outcomes

Low risk

The propacetamol and placebo ampoules were supplied in identical packages. The code remained blinded until the end of the study.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

9/88 participants withdrew for various reasons ‐ unclear which arm participants withdrew from and if this was after receiving intervention

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (40 propacetamol, 39 placebo)

Landwehr 2005

Methods

Randomized, double‐blinded, placebo‐ and active‐controlled

Medications administered 30 min before arrival in the recovery area

Participants

Type of surgery: retinal

Propacetamol group

Entered/completing: 12/12

Age (mean, SD): 52 ± 18

Sex (male, %): 67

Metamizole group

Entered/completing: 13/13

Age (mean, SD): 60 ± 19

Sex (male, %): 31? (data reported in error)

Placebo group

Entered/completing: 13/13

Age (mean, SD): 58 ± 22

Sex (male, %): 69

Interventions

Intervention: 1 g paracetamol in 100 ml over 15 min

Active control: 1 g metamizol

Placebo: 100 ml normal saline

Outcomes

Pain intensity at rest and on coughing (VRS, VAS)

Opioid consumption (tilidine)

Patient satisfaction (categorical)

Source of funding

The study was in part financed by a grant from Bristol‐Myers Squibb GmbH, München, Germany

Were treatment groups comparable at baseline?

Yes: demographics

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated code

Allocation concealment (selection bias)

Low risk

Code prepared at a remote site and sealed in sequentially numbered, opaque envelopes

Blinding (performance bias and detection bias)
All outcomes

Low risk

Infusions were made to look identical

Incomplete outcome data (attrition bias)
All outcomes

Low risk

5 participants in placebo group had incomplete data, imputed by LOCF. It appears that all other participants contributed data at all time points for all outcomes.

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section. Some adverse event data listed only as P values.

Size

High risk

Fewer than 50 participants per arm of the study (12 propacetamol, 13 metamizole, 13 placebo)

Lee 2010

Methods

Randomized, controlled, single dose study evaluating outcomes 6 h postop

Medication was administered 30 min before the end of surgery

Participants

Type of surgery: thyroidectomy

Paracetamol group

Entered/completing: 20/20

Age (mean, SD): 44.7 +/‐ 7.3

Sex (male, %): 0

Control (normal saline)

Entered/completing: 20/20

Age (mean, SD): 46.3 +/‐ 9.5

Sex (male, %): 0

Ketorolac

Entered/completing: 20/20

Age (mean, SD): 46.1 +/‐ 9.9

Sex (male, %): 0

Interventions

Paracetamol: 1 g IV over 15 min administered 30 min before the end of surgery

Normal saline; ketorolac 30 mg; paracetamol 700 mg/morphine 3 mg (not included in our analysis). All administered 30 min before end of surgery.

Outcomes

Primary: degree of pain (VAS 0 to 10)

Secondary: side effects, respiratory depression, degree of satisfaction, incidence of rescue medication

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes: demographics; duration of surgery and anesthesia

Details of preoperative pain

Participants excluded if medicated with drugs that could affect analgesic effect before the operation

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Anesthesiologists were blinded. Manuscript did not specifically state if participants were blinded. Also, no description of blinding methods.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No dropouts ‐ complete data set obtained for all participants.

Selective reporting (reporting bias)

Unclear risk

All outcomes from Methods section reported in Results section. Incidence of rescue medication reported in Results but not mentioned in Methods.

Size

High risk

Fewer than 50 participants per arm of the study (20 paracetamol, 20 placebo, 20 ketorolac)

Leykin 2008

Methods

Randomized, double‐blind, active‐controlled study

Medications administered 15 min before discontinuation of anesthesia

Participants

Type of surgery: functional endoscopic sinus

Propacetamol group

Entered/completing: 25/25

Age (mean, SD): 32 ± 10

Sex (male, %): 72

Parecoxib group

Entered/completing: 25/25

Age (mean, SD): 34 ± 12

Sex (male, %): 76

Interventions

Intervention: 2 g propacetamol over 15 min

Control: 40 mg IV parecoxib

Outcomes

Pain intensity (VAS) and derived SPID

Opioid consumption (morphine)

Patient satisfaction (categorical)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics; type of procedure. Intraoperative and postoperative hemodynamic variables also reported to be similar, but no data shown.

Details of preoperative pain

Participants with chronic pain requiring major analgesics, sedatives, or corticosteroids were excluded

Notes

Participants had only mild pain at baseline

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomization

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Study drugs mixed by physician not involved in study. Double‐dummy technique employed.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Analyses on ITT population, but no mention of imputation method

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (25 propacetamol, 25 parecoxib)

Ma 2003

Methods

Randomized, double‐blinded, double‐dummy, active‐controlled

Medication administered when baseline pain reached moderate‐to‐severe intensity

Participants

Type of surgery: thoracic and abdominal elective

Propacetamol group

Entered/completing: 20/20

Age (mean, SD): unclear

Sex (male, %): unclear

Pethidine group

Entered/completing: 20/20

Age (mean, SD): unclear

Sex (male, %): unclear

Interventions

Intervention: 2 g propacetamol in 100 ml saline

Control: 50 mg pethidine IM

Outcomes

Pain intensity (VAS, VRS) and derived SPID

Pain relief (VAS, VRS) and derived TOTPAR

Time to onset and duration of analgesia

Global evaluation (categorical)

Source of funding

Unclear ‐ one author was an employee of Squibb Pharmaceuticals

Were treatment groups comparable at baseline?

Yes: demographics, disease categories, operation categories, anesthesia methods and duration, vital signs, hepatorenal function, and blood cell count

Details of preoperative pain

Unclear

Notes

Chinese language article with abstract and data in English

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Chinese article ‐ unable to ascertain

Allocation concealment (selection bias)

Unclear risk

Chinese article ‐ unable to ascertain

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐dummy technique

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Chinese article ‐ unable to ascertain

Selective reporting (reporting bias)

Unclear risk

Chinese article ‐ unable to ascertain

Size

High risk

Fewer than 50 participants per arm of the study (20 propacetamol, 20 pethidine)

Maghsoudi 2014

Methods

Randomized, double‐blind, placebo‐controlled multiple dose, 24‐hour study

Medication was administered 30 min after extubation

Participants

Type of surgery: percutaneous nephrolithotomy

Paracetamol group

Entered/completing: 50/50

Age (mean, SD): 44.48 +/‐ 12.92

Sex (male, %): 34 (68%)

Placebo group

Entered/completing: 50/50

Age (mean, SD): 42.56 +/‐ 13.57

Sex (male, %): 40 (80%)

Interventions

Paracetamol: 100 ml normal saline and 1 g paracetamol IV 30 min after extubation and every 8 h until 24 h (4 g total)

100 ml IV normal saline 30 min after extubation and every 8 h until 24 h

Outcomes

Primary: pain intensity (VAS) over first 6 h and 24 h after extubation, demand for opioid analgesia (pethidine 25 to 50 mg IM up to 200 mg per day), total pethidine dose consumed

Secondary: adverse effects

Source of funding

Not mentioned

Were treatment groups comparable at baseline?

Yes ‐ age, BMI, stone size, operative time, baseline VAS. No mention if # of males balanced – 40 versus 34.

Details of preoperative pain

Participants were excluded if they reported use of a NSAID or other analgesic less than 12 h before prescribing the study medications. Also excluded if painful physical conditions that may affect pain assessment after percutaneous nephrolithotomy

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Balanced blocked randomization; randomization schedule was prepared by someone that was blinded to the study.

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

“Serums containing placebo and paracetamol, identical in color and appearance were prepared by an assistant and administered by nursing personnel blinded to the study.” Other group blinded was not specifically stated but assumed to be participants.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Per Results, 2 participants did not complete the study but no additional information was provided. No deviations from the protocol was also noted.

Selective reporting (reporting bias)

Low risk

Frequency of VAS < or > 4 was not mentioned as an outcome in Methods (Table 2)

Size

Unclear risk

50 to 199 participants per arm of the study (50 paracetamol, 50 placebo)

Marty 2005

Methods

Randomized, single dose, double‐blind, active‐controlled parallel‐group

Medication administered when baseline pain reached moderate‐to‐severe intensity

Participants

Type of surgery: gynecological

Paracetamol group

Entered/completing: 80/80

Age (mean, SD): 38.3 ± 12.8

Sex (male, %): 0

Propacetamol group

Entered/completing: 81/81

Age (mean, SD): 33.9 ± 12.0

Sex (male, %): 0

Interventions

Intervention: paracetamol 1g IV in 100 ml solution over 15 min

Active control: propacetamol 2 g in 100 ml solution

Outcomes

Primary outcome: tolerability, including pain at infusion site

Pain intensity (VRS, VAS)

Number of participants requesting rescue medication

Patient satisfaction (categorical)

Source of funding

Not mentioned, but senior author was employee of Bristol Myers Squibb

Were treatment groups comparable at baseline?

Yes: weight, type of surgery, baseline pain intensity at surgical site. No ‐ age: 38.3 paracetamol versus 33.9 propacetamol.

Details of preoperative pain

Patients with any painful physical condition (other than postoperative pain) were excluded.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Participants were randomly assigned in a 1:1 ratio according to a computer‐generated list of numbers to either group

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Study drugs mixed by pharmacist or nurse not involved in the study, were administered as a 100 ml solution infused over 15 min

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

"A total of 163 women were enrolled and 161 received the single infusion of study medication. All remaining 161 patients including 2 patients (1 in each group) who did not meet eligibility criteria, were included in the ITT population and analyses of demographic characteristics, tolerability, and efficacy". Not clear if data were imputed.

Selective reporting (reporting bias)

Low risk

Free of selective reporting. All outcomes from Methods section reported in Results section.

Size

Unclear risk

50 to 199 participants per arm of the study (80 paracetamol, 81 propacetamol)

Mimoz 2001

Methods

Randomized, placebo‐ and active‐controlled

Medications administered at completion of surgery

Participants

Type of surgery: hepatic resection

Propacetamol group

Entered/completing: unclear/38

Age (median, range): 49 (28 to 75)

Sex (male, %): 40

Nefopam group

Entered/completing: unclear/36

Age (median, range): 57 (21 to 75)

Sex (male, %): 53

Placebo group

Entered/completing: unclear/38

Age (median, range): 57 (27 to 75)

Sex (male, %): 58

Interventions

Intervention: 2 g propacetamol over 15 min

Control: 20 mg nefopam over 60 min

Placebo: no treatment

Outcomes

Primary: opioid consumption (morphine via PCA)

Pain intensity (VAS)

Patient satisfaction (categorical)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: sex, weight, height, ASA physical status, duration of surgery and anesthesia, sufentanil and midazolam cumulative doses, VAS score at extubation, and morphine dose for titration

Participants in the propacetamol group were younger versus other 2 groups. Compared with the propacetamol group, participants in the nefopam group had lower VAS scores at extubation and longer intervals between the completion of hepatic resection and extubation.

Details of preoperative pain

Participants receiving chronic anaΙgesic or anti‐inflammatory treatment were excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

High risk

Open study

Blinding (performance bias and detection bias)
All outcomes

High risk

Open study

Incomplete outcome data (attrition bias)
All outcomes

Low risk

From 120 participants 8 were withdrawn for various reasons. Data from all remaining participants were used in the analyses.

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (38 propacetamol, 36 nefopam, 38 placebo)

Mitra 2012

Methods

Randomized, double‐blind, parallel‐group controlled trial, multiple dose, active‐controlled. First dose after spinal block regression to T10.

Participants

Type of surgery: cesarean section

Paracetamol group

Entered/completing: 101/101

Age (mean, SD): 25.92 ± 3.09

Sex (male, %): 0

Tramadol group

Entered/completing: 103/103

Age (mean, SD): 26.04 ± 3.65

Sex (male, %): 0

Interventions

Diclofenac 100 mg suppository for all participants starting at the ‘end of surgery’ and every 8 h for 24 h

Paracetamol IV in 10 cc of NS (no mention of injection time), 1 g every 6 h beginning at block regression to T10

Tramadol 75 mg IV in 10 cc NS per the above protocol

Outcomes

Primary: summed pain intensities during the entire observation period, calculated as the sum of time‐weighted pain intensity scores as an area under the curve (AUC). NRS at rest and movement at 0, 1, 2, 4, 8, 12, 24 h

Secondary: use of supplementary rescue analgesic (pethidine 30 mg IV, administered if the participant’s NRS scores > 4)

Source of funding

Grant received from the Department of Science & Technology (DST), Ministry of Science & Technology, Government of India

Were treatment groups comparable at baseline?

Yes ‐ age BMI, surgical duration, blood loss, NRS at rest and movement. No ‐ BP and HR lower in acetaminophen group

Details of preoperative pain

Participants receiving long‐term analgesics were excluded

Notes

Primary analysis plan was not pursued because of a non normal distribution of pain scores. Instead medians and interquartile ranges were reported and compared for each time point at rest and at movement. This includes time at 4 h. Use of rescue medications over the entire time period was summarized without specific information as to the time for request.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Using computer‐generated random number tables

Allocation concealment (selection bias)

Low risk

Coded, sealed, opaque envelopes

Blinding (performance bias and detection bias)
All outcomes

Low risk

Both the test drugs (tramadol and acetaminophen) were drawn up in similar (Dispovan, Faridabad, Haryana, India) 10 ml coded syringes and diluted with normal saline so as to make the final volume of injection to 10 ml. Participants and assessors were blinded to assignment, but blinding success not tested.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No missing data

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

Unclear risk

50 to 199 participants per arm of the study (101 paracetamol, 103 tramadol)

Moller 2005a

Methods

Randomized, double‐dummy, placebo and active‐controlled

Medication administered when baseline pain reached moderate‐to‐severe intensity within 4 h after surgery

Participants

Type of surgery: third molar extraction

Paracetamol group

Entered/completing: 51/51

Age (mean, SD): 24.5 ± 2.9

Sex (male, %): 69

Propacetamol group

Entered/completing: 51/51

Age (mean, SD): 24.3 ± 3.6

Sex (male, %): 57

Placebo group

Entered/completing: 50/50

Age (mean, SD): 24.5 ± 2.8

Sex (male, %): 68

Interventions

Intervention: IV paracetamol 1 g

Control: propacetamol 2 g

Placebo: 100 ml saline, or 100 ml solution (double‐dummy)

Outcomes

Primary outcome: pain relief (VRS)

Maximum pain relief, time of maximum pain relief, time to onset of pain relief, TOTPAR

Pain intensity (VRS, VAS) and derived summary measures

Time to rescue medication (oral ibuprofen 400 mg)

Global evaluation (categorical)

Source of funding

Supported by the Bristol‐Myers Squibb Company

Were treatment groups comparable at baseline?

Yes: demographics and baseline postoperative pain

Details of preoperative pain

Participants with other painful physical conditions were excluded

Notes

Propacetamol and paracetamol were compared to placebo and then propacetamol was compared to paracetamol

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Treatments were allocated according to block randomization (each block, n = 6)

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐dummy technique employed

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"Treatments were randomized among 152 patients. No patients withdrew from the study and all patients were evaluated for efficacy and safety".

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

Unclear risk

50 to 199 participants per arm of the study (51 paracetamol, 51 propacetamol, 50 placebo)

Moller 2005b

Methods

Randomized, double‐blinded, triple‐dummy, active‐ and placebo‐controlled

Medication administered when baseline pain reached moderate‐to‐severe intensity within 4 h after surgery

Participants

Type of surgery: third molar extraction

Propacetamol group

Entered/completing: 50/50

Age (mean, SD): 24.2 (range 18 to 39)

Sex (male, %): 46

Placebo group

Entered/completing: 25/25

Age (mean, SD): 23.4 (range 20 to 29)

Sex (male, %): 44

Interventions

Intervention: 2 g propacetamol 15 min infusion

Intervention: 2 g propacetamol 2 min bolus (not included in our analysis)

Control: oral acetaminophen (not included in our analysis)

Placebo: triple‐dummy, exact details not described

Outcomes

Primary: time to analgesia onset (double‐click stopwatch method)

Pain relief (categorical) and derived summary scores

Pain intensity (VAS) and derived summary scores

Global evaluation (categorical)

Duration of analgesia (time when 50% of participants in a group requested rescue medication, oral ibuprofen 600 mg)

Source of funding

The study was supported by a grant from Bristol–Myers Squibb

Were treatment groups comparable at baseline?

Yes: sex, weight, baseline pain intensity. Age appears to be similar between the 2 groups included in our analysis.

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated randomization schedule assigned treatments to sequential patients

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

A triple‐dummy technique was employed

Incomplete outcome data (attrition bias)
All outcomes

Low risk

"Treatments were randomized between 175 patients. No patients withdrew from the study and all 175 patients were evaluated by the intent‐to‐treat analyses and for safety".

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

Unclear risk

50 to 199 participants per arm of the study (50 propacetamol, 25 placebo)

Mowafi 2012

Methods

Randomized, investigator‐blinded, parallel‐group study with active and placebo control, first dose at skin closure, outcomes X 24 h

Participants

Type of surgery: variety of lower abdominal surgery (bowel resection, abdominal hysterectomy, abdominal myomectomy, radical prostatectomy)

Paracetamol group

Entered/completing: 20/20

Age (mean, SD): 49.4 ± 18.4

Sex (male, %): 20%

Placebo group

Entered/completing: 20/19

Age (mean, SD): 48.5 ± 14.4

Sex (male, %): 25%

Lornoxicam group

Entered/completing: 20/20

Age (mean, SD): 52.8 ± 16.1

Sex (male, %): 30%

Interventions

Paracetamol: 1 g every 6 h in 100 cc IV x 24 h

Placebo: 100 cc IV every 6 h x 24 h

Lornoxicam: 16 mg in 100 cc saline at time 0 and 8 mg at time 12 h

All:

PCA pump containing morphine was attached to the participant in a separate IV cannula. The pumps were programmed to administer morphine 1 mg boluses at 10 min intervals and total of 20 mg through 4 h limits.

Outcomes

Primary: pain score via VPS during rest and coughing at 1st, 2nd, 4th, 8th, 12th and 24th postoperative h

Secondary: heart rate, blood pressure, respiratory rate, and morphine consumption of the participants were assessed at 1st, 2nd, 4th, 8th, 12th and 24th

postoperative h

Adverse effects, including nausea, vomiting, itching, sweating, urinary retention, sedation, respiratory depression, hypotension, tachycardia, bradycardia,

gastric irritation, increased bleeding from the wound, hematemesis, and melena were recorded and managed accordingly. The Ramsay sedation score [16] was used to evaluate the level of sedation.

Source of funding

Deanship of Scientific Research of Dammam University

Were treatment groups comparable at baseline?

Reports no significant differences for study groups including operative time but states P value < 0.05 for all demographics, likely an error

Details of preoperative pain

Patients who received pain medications on the day prior to surgery and chronic drug abusers were excluded

Notes

Sample size based on internal pilot and VPS difference of 3

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Online research randomizer (www.randomizer.org)

Allocation concealment (selection bias)

Unclear risk

No information reported

Blinding (performance bias and detection bias)
All outcomes

Low risk

No mention of participants blinding. “The anesthetist who provided anesthesia and the on who followed up with the patients in the ward for assessment were blinded to the study drug given. Sealed and enclosed 100 ml bags containing either normal saline or the study drugs were used. The color of lornoxicam solution is yellow; to maintain blinding, the containers for all solutions were covered with aluminium foil during administration”.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Only one dropout in entire study

Selective reporting (reporting bias)

Unclear risk

Opioid consumption measured at 1, 2 and 4 h, but not reported

No results available on clinicaltrials.gov

Size

High risk

Fewer than 50 participants per arm of the study (20 paracetamol, 20 placebo, 20 lornoxicam)

Ohnesorge 2009

Methods

Randomized, double‐blind, placebo‐ and active‐controlled

Medications administered 20 min before the end of surgery (and at 4, 10 and 16 h postoperatively)

Participants

Type of surgery: breast cancer (segmental or mastectomy)

Paracetamol group

Entered/completing: 30/27

Age (mean, SD): 56 ± 13

Sex (male, %): 41

Metamizole group

Entered/completing: 30/26

Age (mean, SD): 52 ± 12

Sex (male, %): 55

Placebo group

Entered/completing: 30/26

Age (mean, SD): 58 ± 14

Sex (male, %): 55

Interventions

Intervention: IV paracetamol 1 g/100 ml normal saline over 10 to 15 min

Control: metamizole 1 g IV

Placebo: 100 ml normal saline

Outcomes

Pain intensity (NRS)

Cognitive function (TDT, DSST)

All other outcomes assessed at 24 h

Source of funding

Supported by Department of Anesthesiology and Bristol‐Myers Squibb

Were treatment groups comparable at baseline?

Yes: demographics, duration of surgery, nature of surgery, ASA risk category

Details of preoperative pain

Not reported

Notes

From 2 h postoperatively onwards, average pain ratings were below 2.5/10 in all groups. No data could be used in meta‐analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

"random list"

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Treatments appeared identical

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

27/30 paracetamol and 26/30 in other groups completed study ‐ dropouts for various reasons specified. It appears that only data from those completing study were analyzed.

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section. Minor omissions of complete data for some safety outcomes.

Size

High risk

Fewer than 50 participants per arm of the study (30 paracetamol, 30 metamizole, 30 placebo)

Omar 2011

Methods

Blinded, randomized, controlled, parallel‐group, multidose trial. Intervention start at the ‘end of surgery’.

Participants

Type of surgery: elective cesarean section

Paracetamol group

Entered/completing: 40/40

Age (mean, SD): 30.80 ± 4.79

Sex (male, %): 0

Normal saline group

Entered/completing: 40/40

Age (mean, SD): 29.60 ± 5.20

Sex (male, %):0

Interventions

Paracetamol: 1 g IV in 100 cc start at end of surgery, then every 6 h x 24 h

Control: 100 cc NS start at end of surgery, then every 6 h x 24 h

All: every participant received 0.2 mg intrathecal morphine at the time of spinal placement. Clinically this intervention has an expected duration of action of up to 18 h. Pethidine for rescue analgesia

Outcomes

Primary: number of participants requiring rescue analgesic drug use x 24 h

Secondary: visual analog scale (VAS) was used to evaluate pain level (0 = no pain to 10 = worst pain) at 6, 12 and 24 h postoperatively by a resident and nurse who did not know about the treatment protocols. Satisfaction was evaluated at 12 and 24 h postoperatively (1 = very unsatisfied to 5 = very satisfied).

Source of funding

None mentioned

Were treatment groups comparable at baseline?

Yes, but no data on surgical duration or whether or not a participant had a repeat cesarean section

Details of preoperative pain

Participants with history of chronic abdominal pain or treated with analgesics were excluded from the study

Notes

No enrolment flow chart. When a spinal failed, a participant was dropped, likewise for participants with intraoperative complications for example, but unclear when participants were enrolled or randomized.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Table of randomization

Allocation concealment (selection bias)

Low risk

Sealed envelope

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Participant blinding not addressed. Personnel blinding per statement except that the chief resident was not blinded.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No missing data reported. Appears that all participants completed the study.

Selective reporting (reporting bias)

High risk

Very limited outcomes (rescue analgesia, pain, and satisfaction scores). No side effects addressed at all.

Size

High risk

Fewer than 50 participants per arm of the study (40 paracetamol, 40 placebo)

Oncul 2011

Methods

Double‐blind, double‐dummy, parallel‐group, active‐controlled randomized study

Participants

Type of surgery: bimaxillary osteotomy

Paracetamol group

Entered/completing: 15/15

Age (median, range): 21 (16 to 38)

Sex (male, %): 27

Diclofenac group

Entered/completing: 15/15

Age (median, range): 24 (17 to 42)

Sex (male, %): 27

Interventions

All: 160 mg of articaine LA with epinephrine to site of surgery at the start of case. General anesthesia, no opioids. Postoperative on demand rescue analgesic of 75 mg diclofenac IM. Observation period x 24 h.

Paracetamol: intravenous solution of 1 g x 1 within 15 min of mucosal closure + IM placebo

Diclofenac: IV solution of 1 g of placebo x 1 within 15 min of mucosal closure + IM 75 mg diclofenac

Outcomes

Primary: the severity of postoperative pain was evaluated on the VAS after 30 min, and then at 1, 2, 4, 6, 8, 12, and 24 h

Secondary: systolic blood pressures and heart rates were also recorded at the same times. The number and time of diclofenac rescue were also recorded. Early and late side effects during the first 30 min and after 24 h, such as nausea, vomiting, hypotension, sedation, cyanosis, hypertension, facial oedema, and urticaria, were also recorded. Patients’ satisfaction was assessed 24 h postoperatively using a 3‐point scale (1 = not satisfied, 2 = satisfied, 3 = very satisfied).

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: demographics, BMI, duration of surgery

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Random allocation to 2 groups, no further info

Allocation concealment (selection bias)

Low risk

Sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

“a staff nurse premixed an intravenous solution containing either paracetamol or placebo 1 g. The same nurse gave an intramuscular injection of diclofenac 75 mg or placebo as assigned”. No mention of whether placebo and intervention appeared identical.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Appears all participants completed study and data were collected on all

Selective reporting (reporting bias)

Low risk

All outcomes mentioned in Methods reported in Results

Size

High risk

Fewer than 50 participants per arm of the study (15 paracetamol, 15 diclofenac)

Oreskovic 2014

Methods

Double‐blind, randomized, active‐controlled, parallel‐group study with intervention at end of surgery x 24 h for outcomes

Participants

Type of surgery: total hip arthroplasty under spinal anesthesia

Paracetamol group

Entered/completing: 43/43

Age (mean, SD): 57.7 (13.8)

Sex (male, %): 39.5

Metamizol group

Entered/completing:51/51

Age (mean, SD): 62.2 (12.4)

Sex (male, %):29.4

All: morphine PCA at baseline

Interventions

Paracetamol: IV 1 g paracetamol every 8 h x 24 h, start at ICU admission

Metamizol: IV 1.5 g every 8h x 24 h, start at ICU admission

All: PCA morphine with continuous setting 1 to 2 mg/h (based on participant weight), 1 mg bolus with 15 min lockout x 24 h

Outcomes

Primary: pain intensity in the first 24 h after surgery. Total pain over the study period was calculated as area under the pain/time curve. VAS 0 to 100 with a 10 cm ruler.

Secondary: pain was assessed at time points of 1, 2, 3, 4, 6, 8, 10, 14, 18 and 22 h post‐baseline

Amount of morphine consumption in 24 h

Source of funding

No financial support

Were treatment groups comparable at baseline?

Yes: demographics, estimated blood loss, duration of surgery

Details of preoperative pain

None

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomly generated list

Allocation concealment (selection bias)

Unclear risk

Not mentioned

Blinding (performance bias and detection bias)
All outcomes

Low risk

“Research team and the patients were not familiar with the information about products that patients received. Drugs were prescribed by an independent doctor and administered by nurses not involved in the research. Nurses not involved in the research recorded VAS scale results. Independent blinded researchers performed clinical observations”.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All randomized participants completed study. No mention of how missing data were imputed.

Selective reporting (reporting bias)

High risk

No reporting of adverse events

Size

High risk

Fewer than 50 participants per arm of the study (43 paracetamol, 51 metamizol)

Paech 2014

Methods

Randomized, double‐blind, double‐dummy, parallel‐group, placebo‐controlled clinical trial x 24 h, starting with intervention immediately postoperatively

Participants

Type of surgery: elective cesarean delivery under spinal anesthesia

Paracetamol group

Entered/completing: 32/32

Age (median, IQR): 31 (28 to 34)

Sex (male, %): 0

Control group

Entered/completing:23/23

Age (median, IQR): 30 (28 to 35)

Sex (male, %): 0

Parecoxib group

Entered/completing: 30/30

Age (median, IQR): 30 (26 to 35)

Sex (male, %): 0

Interventions

IV solutions (200 ml for infusion over 15 min or 2 ml for bolus injection after delivery) and oral capsules of identical appearance (for administration after surgery). Study regimen started immediately after delivery.

All:

1. Pethidine patient‐controlled epidural analgesia x at least 24 h, 20 mg on demand, 15 min lockout

2. If the verbal numerical rating score for pain was > 6 with movement or > 3 at rest at any time, supplementary analgesia was available in the form of immediate‐release tramadol 50 to 100 mg oral 2‐hourly on demand (maximum dose 600 mg across 24 h)

3. Thereafter, analgesia was at the discretion of the attending anesthetist or acute pain service

4. Postoperative pruritus was treated with IV ondansetron 4 mg 6‐hourly on demand or, if this was ineffective, IV naloxone 50 µg hourly on demand

Paracetamol: 2 g IV x 1 after delivery, then oral 1 g at 6, 12 and 18 h and appropriate placebos

Parecoxib: 40 mg IV x 1 after delivery, then oral celecoxib 400 mg at 12 h and placebos

Parecoxib + paracetamol: 40 mg and 2 g IV after delivery, then paracetamol 1 g oral at 6, 12 and 18 h + celecoxib 400 mg oral at 12 h (not included in our analysis)

Control: saline placebos and capsules after delivery and at 6, 12 and 18 h respectively as appropriate

Outcomes

Primary: 24‐hour postoperative patient‐controlled epidural pethidine use

Secondary: the main secondary outcomes were the 0 to 24 h AUC pain scores with movement, the quality of recovery score and the "SDQ" score

1. Postoperative pain measured as verbal numerical rating score (VRS) of 0 to 10 at rest and movement at 6, 12, 24 and 48 h

2. VRS sedation scores at the same times. Area under the curve (AUC) for rest and movement pain scores over 0 to 24 h

3. Presence of gastrointestinal upset, nausea or epigastric pain at 24 h

4. Satisfaction with analgesia (0 to 10 VRS and ratings of excellent, good, fair, or poor) at 24 h

5. Severity of overall nausea, sedation, and pruritus (VRS) at 24 h

6. OR score, the opioid related "SDQ" score and a Modified Brief Pain Inventory (short‐form)

7. At 48 h, pain and sedation scores were recorded and the presence of urinary retention post‐catheter removal or observed respiratory depression (respiratory rate < 8 breaths per minute or sedation score of 3 representing 'difficult to rouse') assessed

Source of funding

Investigator‐initiated research grant from Pfizer Australia

Were treatment groups comparable at baseline?

Yes: age, ASA II, BMI, gravidity, parity, previous cesarean section

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“A randomization sequence for four groups in a 1:1:1:1 ratio was generated by the hospital Pharmacy Department using a computer‐generated random number sequence”

Allocation concealment (selection bias)

Low risk

“Allocation was by selection of the next sealed and coded study drug package and occurred intraoperatively”.

Blinding (performance bias and detection bias)
All outcomes

Low risk

All observers were blinded to study group allocation. Medications prepared to look identical. No further detail.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

ITT analysis with LOCF, plus per‐protocol analysis and no dropouts

Selective reporting (reporting bias)

Unclear risk

Did not report all adverse event data

Size

High risk

Fewer than 50 participants per arm of the study (32 paracetamol, 23 placebo, 30 parecoxib)

Peduto 1998

Methods

Randomized, placebo‐controlled, double‐blind

Medications administered after extubation

Participants

Type of surgery: orthopedic

Propacetamol group

Entered/completing: 46/41

Age (mean, SD): 62.6 ± 8.3

Sex (male, %): 31

Placebo group

Entered/completing: 51/45

Age (mean, SD): 60.5 ± 9.6

Sex (male, %): 32

Interventions

Intervention: propacetamol 2 g in 100 ml 5% dextrose over 15 min

Placebo: 5% dextrose 100 ml

Outcomes

Opioid consumption (morphine via PCA)

Pain intensity (VRS, VAS)

Global efficacy (VRS)

Source of funding

Financially supported by UΡSA MEDΙCA SPA

Were treatment groups comparable at baseline?

Yes: demographics, duration of surgery, baseline pain intensity, pre‐intervention morphine use

Details of preoperative pain

None

Notes

Opioid consumption and global efficacy assessed at 24 h

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Balanced block 2:2 randomization

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Identical vials for further dilution

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Inadequate intention‐to‐treat. "A total of 97 patients entered the study and 89 of them were evaluated". 8 were withdrawn from efficacy analyses due to malfunctioning of PCA. All of these 89 patients were used in the efficacy analyses including 3 cases of premature discontinuation of the study due to lack of efficacy and 1 withdrawal of consent.

Time point of premature discontinuation is not defined

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (46 propacetamol, 51 placebo)

Salonen 2009

Methods

Prospective, randomized, double‐blinded and placebo‐controlled add‐on study with 3 parallel groups, paracetamol given 5 min after ketoprofen that was given after surgery, both likely within 1 hour of surgery end, but exact time not given

Participants

Type of surgery: tonsillectomy

Paracetamol 1 g group

Entered/completing: 39/39

Age (mean, SD): 22 (6)

Sex (male, %): 15, 40%

Placebo group

Entered/completing: 38/38

Age (mean, SD): 38 (10)

Sex (male, %): 18, 47%

Interventions

Paracetamol 1 g: 15 min infusion, 5 min after ketoprofen IV x 1

Paracetamol 2 g: 15 min infusion, 5 min after ketoprofen IV x 1 (not included in our analysis)

Normal Saline: 15 min infusion 5 min after ketoprofen IV X 1

ALL: 2 µg/kg fentanyl intraoperatively, ketoprofen 1 mg/kg in 10 cc saline 5 min after surgery, oxycodone 2 mg IV was provided for rescue analgesia if VAS rest was > 30/100 mm or VAS swallowing > 50/100 mm. The oxycodone dose was repeated at 15‐min intervals until pain had diminished (VASr < 30mm and VASs < 50mm) x 6 h

Outcomes

Primary: proportion of patients requiring oxycodone for rescue analgesia to maintain VASr (resting) < 30 mm and VASs (swallowing) < 50 mm over the first 6 h

Secondary: VASr&s at 1, 2, 3, 4, and 6 h after the surgery and at discharge. Length of time until the first dose of rescue analgesic, the number of oxycodone doses during the first 6 h after surgery, the sedation score at discharge, and the incidence of adverse effects.

Source of funding

Absence of external funding specifically mentioned

Were treatment groups comparable at baseline?

Unclear: no statistical analysis was provided for the group characteristics

Details of preoperative pain

Not reported

Notes

119 participants enrolled. 5 withdrew consent before randomization.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated

Allocation concealment (selection bias)

Low risk

Sealed envelopes

Blinding (performance bias and detection bias)
All outcomes

Low risk

“To ensure blinding, the syringes were prepared by a nurse otherwise not involved in the study, and the patients, surgeons and study nurses obtaining the outcome data were blinded to the treatment arms”. “Thus, we used an approach where all patients were provided similar infusions prepared by the study nurse. Because a paracetamol infusion is colorless, does not contain visible particles and does not irritate veins, we believe that the blinding should have performed sufficiently. Unfortunately, we did not test this in the present study.”

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All randomized participants completed the study and appear to have contributed data for all outcomes

Selective reporting (reporting bias)

High risk

6 h pain scores measured but not reported, patient characteristics analyzed but no statistical comparison provided, insufficient detail regarding adverse effects, including nausea. Adverse events were not reported group‐specific but in aggregate for the entire cohort.

Size

High risk

Fewer than 50 participants per arm of the study (39 paracetamol, 38 placebo)

Sanyal 2014

Methods

Prospective, randomized, double‐blind study, parallel‐group, active control x 24 h

Participants

Type of surgery: elective total abdominal hysterectomy with or without bilateral salpingo‐oophorectomy

Paracetamol group

Entered/completing: not stated

Age (mean, SD): not stated

Sex (male, %): 0

Diclofenac group

Entered/completing: not stated

Age (mean, SD): not stated

Sex (male, %): 0

Interventions

Paracetamol: 1 g IV postoperatively every 8 h x 24 h

Diclofenac: 75 mg IM every 8 h x 24 h

Outcomes

Primary: requirement of rescue analgesic (time component not described)

Secondary: VAS (scale not mentioned) for pain at least at 4 and 12 h postoperatively, time until first rescue analgesic administration, patient satisfaction score (scale not mentioned), nausea, vomiting, bronchospasm

Source of funding

None mentioned

Were treatment groups comparable at baseline?

Not described

Details of preoperative pain

Not described

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No information

Allocation concealment (selection bias)

Unclear risk

No information

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

No information

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Unclear how many participants completed the study or what method of analysis was used

Selective reporting (reporting bias)

High risk

No data reported

Size

High risk

Fewer than 50 participants per arm of the study

Shimia 2014

Methods

Double‐blind, randomized, placebo‐controlled. Single dose of intravenous paracetamol within the last 20 min of surgery or placebo.

Participants

Type of surgery: lumbar discectomy

Paracetamol group

Entered/completing: dropouts not reported; presumably 24/24

Age (mean, SD): 46.50 ± 14.07

Sex (male, %): 46.2% for both groups

Placebo group

Entered/completing: dropouts not reported; presumably 28/28

Age (mean, SD): 52.25 ± 11.46

Sex (male, %): 46.2% for both groups

Interventions

Paracetamol: 1 g in 100 ml normal saline. Duration of administration not stated.

100 ml normal saline. Duration of administration not stated.

Outcomes

Primary: pain on 0 to 10 VAS at 1, 6, 12, 18, 24 h after surgery

Morphine dosage for the first 24 h postop

Secondary:

Adverse effects

Source of funding

Tabriz University of Medical Sciences

Were treatment groups comparable at baseline?

Yes: age, sex

Details of preoperative pain

Patients with preoperative treatment with narcotics, benzodiazepines, or clonidine were excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomization method not described

Allocation concealment (selection bias)

Unclear risk

No information

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

All local anesthetic solutions and adjuvant drugs were prepared by an anesthesiologist who was not involved in the performance of the study agents, patient care, or data collection. No mention that interventions appeared identical.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Unclear if all participants completed the study

Selective reporting (reporting bias)

Unclear risk

Adverse effects assessment mentioned in methods, but article states there were no side effects related to treatment (without any detail)

Size

High risk

Fewer than 50 participants per arm of the study (24 paracetamol, 28 placebo)

Siddik 2001

Methods

Randomized, double‐blind, double‐dummy, placebo‐ and active‐controlled

Medications administered immediately after surgery

Participants

Type of surgery: cesarean delivery

Propacetamol group

Entered/completing: 20/20

Age (mean, SD): 31 ± 4.6

Sex (male, %): 0

Diclofenac group

Entered/completing: 20/20

Age (mean, SD): 31.4 ± 6

Sex (male, %): 0

Placebo group

Entered/completing: 20/20

Age (mean, SD): 30.6 ± 5.1

Sex (male, %): 0

Interventions

Intervention: 2 g propacetamol

Control: 100 mg rectal diclofenac

Control: combination of 100 mg rectal diclofenac and 2 g propacetamol (not included in our analysis)

Placebo: double‐dummy, exact details not described

Outcomes

Opioid consumption (morphine via PCA)

Pain intensity at rest and on coughing (VAS 0 to 10)

Global assessment (categorical, at 24 h)

Source of funding

Not reported

Were treatment groups comparable at baseline?

Yes: age, weight, height, parity, and gestationaΙ age

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number table

Allocation concealment (selection bias)

Unclear risk

Patients and staff were unaware of the patients' group assignment

Blinding (performance bias and detection bias)
All outcomes

Low risk

"to ensure blinding of both the parturients and the anaesthesiologist, patients in all groups received both an IV injection and a suppository during the same period"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

From 80 patients one was excluded due to technical problems of the PCA device. Data obtained from the 79 remaining patients were used for the analysis of all outcomes and time points.

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (20 propacetamol, 20 diclofenac, 20 placebo)

Sinatra 2005

Methods

Randomized, double‐blind, double‐dummy, placebo‐controlled

Medications administered on postoperative day 1, when baseline pain reached moderate‐to‐severe intensity (after PCA disconnected)

Participants

Type of surgery: total hip arthroplasty

Paracetamol group

Entered/completing: 49/46

Age (mean, SD): 61.7 ± 16.9

Sex (male, %): 57

Propacetamol group

Entered/completing: 50/44

Age (mean, SD): 59.5 ± 14.2

Sex (male, %): 54

Placebo group

Entered/completing: 52/47

Age (mean, SD): 59.2 ± 13.4

Sex (male, %): 42

Interventions

Intervention: 1 g IV paracetamol in 100 ml solution over 15 min

Control: 2 g propacetamol

Placebo: 100 ml solution

Outcomes

Primary: pain relief (VRS)

Pain intensity (VAS, VRS)

Time to rescue medication (morphine)

Opioid consumption (morphine)

Patient global evaluation

Source of funding

Supported by Bristol‐Myers Squibb Company, Rueil‐Malmaison, France

Were treatment groups comparable at baseline?

Yes: demographics, anesthetic and surgical procedure and baseline pain intensity

Details of preoperative pain

"The overwhelming majority of patients had symptoms of severe debilitating or painful osteoarthritis". Not mentioned if this was similar between groups.

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Unblinded pharmacist was not involved in the study. All study medications were administered as a 100 ml solution infused over 15 min.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

From a total of 156 randomized patients 151 included. "All of these 151 patients were included in the intent‐to‐treat population and analyzed for demographics, efficacy and safety".

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

Unclear risk

50 to 199 participants per arm of the study (49 paracetamol, 50 propacetamol, 52 placebo)

Tiippana 2008

Methods

Randomized, double‐blind, active‐controlled

Medications administered at removal of gall bladder, around 30 min from end of surgery

Participants

Type of surgery: laparoscopic cholecystectomy

Paracetamol group

Entered/completing: 40/39

Age (mean, SE): 38.9 ± 1.8

Sex (male, %): 18

Parecoxib group

Entered/completing: 40/39

Age (mean, SE): 42.9 ± 1.7

Sex (male, %): 28

Interventions

Intervention: paracetamol 1 g IV

Control: paracetamol 1 g IV with dexamethasone 10 mg IV (not included in our analysis)

Control: parecoxib 40 mg IV

Control: parecoxib 40 mg IV with dexamethasone 10 mg IV (not included in our analysis)

Outcomes

Pain intensity at rest and with movement (VAS)

Time to rescue medication (oxycodone)

Opioid consumption (at 24 h onwards only)

Source of funding

Pfizer Finland supplied parecoxib. No other details.

Were treatment groups comparable at baseline?

Yes: age, weight, gender, ASA physical status, the duration of the operation, or the length of stay in hospital

Details of preoperative pain

Patients regularly using analgesics were excluded

Notes

Combination groups not analyzed. Contact author confirmed that doses of paracetamol/parecoxib were administered within half an hour of end of surgery.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Study drugs administered by nurse not otherwise involved in the study, but no further information given

Incomplete outcome data (attrition bias)
All outcomes

Low risk

1/40 in each analyzed group excluded from analysis. It appears that all other participants contributed data for all time points of interest (more participants dropped out after day 1 of study, but were not part of our analysis).

Selective reporting (reporting bias)

Unclear risk

Pain at rest and with motion was recorded every 20 min in PACU 1 and every 30 min in PACU 2, but data not presented for time points 1.5 h, 2 h and 2.5 h

Size

High risk

Fewer than 50 participants per arm of the study (40 paracetamol, 40 parecoxib)

Togrul 2011

Methods

Double‐blind, random allocation to IV paracetamol 30 min before surgery versus IV tramadol 20 min before end of surgery

Participants

Type of surgery: septo‐rhinoplasty

Paracetamol group

Entered/completing: 25/25

Age (mean, SD): 31.5 ± 11

Sex (male, %): 64

Tramadol group

Entered/completing: 25/25

Age (mean, SD): 31.8 ± 10

Sex (male, %): 64

Interventions

Paracetamol infusion 1 g given 30 min before end of surgery

IV tramadol given 30 min (in abstract written 20 min) before end of surgery, dose not stated. In abstract ‐ 1 mg/kg dose is mentioned.

Outcomes

Primary:

Pain intensity on 10 cm VAS

Secondary:

Patient satisfaction, drug side effects, analgesic need

Source of funding

Not stated

Were treatment groups comparable at baseline?

Yes: age, sex, weight, duration of surgery, and anesthesia

Details of preoperative pain

Not reported

Notes

Postoperatively participants could take 500 mg oral paracetamol, up to 3 g/day, and if required, tramadol 0.5 mg/kg as IV bolus

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

No information

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Last paragraph of introduction states it was double‐blind but no additional details were provided

Incomplete outcome data (attrition bias)
All outcomes

Low risk

All participants have completed

Selective reporting (reporting bias)

High risk

Objective state adverse effect and patient satisfaction investigation. Adverse effect not reported. Only nausea % in one group is reported, stating it is higher than in the other group, but no quantitative data. Patient satisfaction not reported.

Size

High risk

Fewer than 50 participants per arm of the study (25 paracetamol, 25 tramadol)

Tunali 2013

Methods

Participants randomized to 3 groups to receive interventions at the time of wound closure (supposedly within 30 min from end of surgery)

Participants

Type of surgery: microsurgical lumbar discectomy and/or laminectomy

Paracetamol group

Entered/completing: 20/18

Age (mean, SD): 46.39 ± 10.06

Sex (male, %): 33

Placebo group

Entered/completing: 20/20

Age (mean, SD): 48.35 ± 9.93

Sex (male, %): 55

Dexketoprofen group

Entered/completing: 20/18

Age (mean, SD): 39.17 ± 11.10

Sex (male, %): 38.9

Interventions

All administered IV in 100 ml infused over 15 min

All participants used IV PCA with morphine

Paracetamol: 1 g every 6 h for 24 h

The study states paracetamol but in discussion says “Paracetamol is an IV formulation of a prodrug of acetaminophen and used as a supplemental analgesic to reduce postoperative pain

Dexketoprofen: 50 mg IV every 8 h for 24 h

Placebo: 100 ml normal saline every 8 h for 24 h

Outcomes

Primary: pain intensity on 0 to 10 VAS at 0, 1, 2, 6, 12, 24 h post‐op but primary outcome not defined

Secondary: sedation on Ramsay score, cumulative PCA morphine consumption at the above time points, adverse effects

Source of funding

No funding

Were treatment groups comparable at baseline?

No: age in dexketoprofen group lower than in 2 other groups; pain at time 0 in dexketoprofen group substantially lower

Details of preoperative pain

Not reported

Notes

Frequency of administration different: every 6 h for paracetamol and every 8 h for dexketoprofen and saline

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

1 person prepared sealed envelopes and another person drew an envelope for each case

Allocation concealment (selection bias)

Unclear risk

Unclear if solutions looked any different

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

The treatment frequency is different (3 times daily versus 4 times daily), true blinding not likely, although study data were collected by a blinded anesthesiologist

Incomplete outcome data (attrition bias)
All outcomes

Low risk

4 participants were excluded, with reasons given. Outcomes seem to be reported in full.

Selective reporting (reporting bias)

Low risk

All outcomes mentioned in Methods reported in Results

Size

High risk

Fewer than 50 participants per arm of the study (20 paracetamol, 20 placebo, 20 dexketoprofen)

Tuncel 2012

Methods

Local wound infiltration versus IV paracetamol versus IV lornoxicam 30 min before extubation. Additional analgesia with tramadol and as required pethidine.

Participants

Type of surgery: laparoscopic renal and adrenal surgery

Paracetamol group

Entered/completing: 20/not reported

Age (mean, SD): not reported

Sex (male, %): not reported

Lornoxicam group

Entered/completing: 20/not reported

Age (mean, SD): not reported

Sex (male, %): not reported

Interventions

Paracetamol 1 g 30 min before extubation, then 5 g in 24 h postop, frequency/timing not reported

0.25% levobupivacaine infiltration to trocar incisions (not included in our analysis)

Lornoxicam: 8 mg IV 30 min before extubation and another 8 mg during 24 h postop. Frequency not reported.

Outcomes

Primary: pain VAS scores

Secondary: cumulative tramadol and pethidine consumption

Source of funding

Not reported

Were treatment groups comparable at baseline?

Not reported

Details of preoperative pain

Not reported

Notes

Abstract

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not reported

Allocation concealment (selection bias)

High risk

Not reported, and not stated to be unblinded

Blinding (performance bias and detection bias)
All outcomes

High risk

Not stated that study was blinded

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Unclear how many participants completed the study

Selective reporting (reporting bias)

High risk

Most of the outcomes not reported

Size

High risk

Fewer than 50 participants per arm of the study (20 paracetamol, 20 lornoxicam)

Unal 2013

Methods

Administration of IV paracetamol versus IV dexketoprofen versus placebo during incision closure

Participants

Type of surgery: total abdominal hysterectomy

Paracetamol group

Entered/completing: 21/20

Age (mean, SD): 48.1 ± 3.6

Sex (male, %): 0

Dexketoprofen group

Entered/completing: 22/20

Age (mean, SD): 47.7 ± 5.9

Sex (male, %): 0

Placebo group

Entered/completing: 21/20

Age (mean, SD): 48.1 ± 4.5

Sex (male, %): 0

Interventions

Paracetamol 1 g/100 ml in 15 min IV infusion, then every 6 h for 24 h

Dexketoprofen: 50 mg in 100 ml 15 min IV infusion, then every 8 h for 24 h

Placebo: normal saline 100 ml 15 min IV infusion, then every 6 h for 24 h

Outcomes

Primary: differences in cumulative 24 h morphine consumption

Secondary: VAS pain scores, adverse events, patient satisfaction

Source of funding

None

Were treatment groups comparable at baseline?

Yes: weight, height, BMI, ASA 1/2, anesthesia duration, surgery duration

Details of preoperative pain

Participants with preoperative pain or regular analgesic use excluded

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated block random allocation

Allocation concealment (selection bias)

Low risk

Sealed, opaque envelopes

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Unblinded person preparing drugs, blinded person assessed outcomes. Unclear if the solutions looked the same.

Drug administration frequency different among groups (3 versus four times daily), so blinding might have been compromised

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Number of dropouts low, evenly distributed among groups and reasons for dropout do not appear to be related to treatment

Selective reporting (reporting bias)

Unclear risk

Incomplete description of methodology for patient satisfaction assessment and incomplete presentation of data

Size

High risk

Fewer than 50 participants per arm of the study (21 paracetamol, 22 dexketoprofen, 21 placebo)

Van Aken 2004

Methods

Randomized, double‐blinded, double‐dummy, placebo‐ and active‐controlled

Medication administered when baseline pain reached moderate‐to‐severe intensity within 3 h after regaining consciousness

Participants

Type of surgery: dental

Propacetamol group

Entered/completing: 31/31

Age (mean, SD): 20.0 ± 4.9

Sex (male, %): 25

Morphine group

Entered/completing: 30/30

Age (mean, SD): 18.8 ± 4.3

Sex (male, %): 39

Placebo group

Entered/completing: 34/34

Age (mean, SD): 20.9 ± 6.6

Sex (male, %): 29

Interventions

Intervention: 2 g propacetamol in 150 ml normal saline over 15 min

Control: 10 mg morphine

Placebo: 150 ml normal saline

Outcomes

Pain intensity (VRS, VAS) and derived summary measures

Pain relief (VRS)

Proportion of patients requesting and time to rescue medication (morphine)

Global assessment (at 10 h)

Source of funding

Supported by a grant from Bristol‐Myers Squibb

Were treatment groups comparable at baseline?

Yes: demographics, duration of surgery, baseline pain intensity

No: the morphine group had a larger proportion of ASA II participants than the placebo group (P value < 0.01)

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

Double‐dummy technique employed

Incomplete outcome data (attrition bias)
All outcomes

Low risk

From 99 patients 4 were excluded due to protocol violations before any data had been collected. "All 95 remaining patients from whom efficacy data were obtained were included in the efficacy analysis".

Selective reporting (reporting bias)

Unclear risk

All outcome from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (31 propacetamol, 30 morphine, 34 placebo)

Varrassi 1999

Methods

Randomized, double‐blinded, double‐dummy, active‐controlled

Medications administered at time of extubation

Participants

Type of surgery: elective hysterectomy

Propacetamol group

Entered/completing: 100/87

Age (mean, SD): 48.4 ± 6.7

Sex (male, %): 0

Ketorolac group

Entered/completing: 100/89

Age (mean, SD): 49.8 ± 9.0

Sex (male, %): 0

Interventions

Intervention: 2 g propacetamol in 100 ml saline over 15 min

Control: 30 mg IV ketorolac

Outcomes

Opioid consumption (morphine via PCA)

Pain intensity (VAS and VRS)

Patient satisfaction (VRS at 12 h)

Source of funding

Supported in part by UPSA MEDICA SPA

Were treatment groups comparable at baseline?

Yes: demographics, duration of surgery, initial pain intensity

Details of preoperative pain

Patients were excluded if they were receiving additional analgesic, antipyretic, or antiinflammatory treatment during the study

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Balanced block (2:2) randomization, each study center receiving 4 case lots

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Propacetamol 2 g or ketorolac 30 mg was administered as an IV infusion (100 ml saline in 15 min). Unclear whether the 2 infusions appeared identical.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

24 patients were excluded before blinding and 2 patients, 1 from each treatment arm, were withdrawn from the study for reasons unrelated to treatment. Then 2 were withdrawn due to lack of efficacy. Remaining patients were 87 for propacetamol and 89 for ketorolac group and were all used in the outcome evaluating cumulative morphine consumption. Number of patients used for the outcomes "evaluation of pain intensity" and "percentage of patients rating pain as severe or very severe" differ.

Selective reporting (reporting bias)

Low risk

Free of selective reporting

Size

Unclear risk

50 to 199 participants per arm of the study (100 propacetamol, 100 ketorolac)

Vuilleumier 1998

Methods

Randomized, double‐blind, active‐controlled

Medications administered at the end of anesthesia

Participants

Type of surgery: various elective

Propacetamol group

Entered/completing: 40/38

Age (mean, SD): 39 ± 13

Sex (male, %): 47

Morphine group

Entered/completing: 40/39

Age (mean, SD): 39 ± 14

Sex (male, %): 49

Interventions

Intervention: 30 mg/kg propacetamol in 150 ml dextrose 5% over 15 min

Control: 0.2 mg/kg morphine IV

Outcomes

Number of patients requiring rescue analgesia (repeat dose of intervention)

Pain intensity (VAS)

Vigilance (trailmaking test)

Source of funding

UPSA Laboratories supplied drugs and covered logistical expenses of study

Were treatment groups comparable at baseline?

Yes: demographics, duration of anesthesia, type of surgery

Details of preoperative pain

Patients taking opioids were excluded

Notes

French language paper

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Unclear risk

Solutions prepared by third party, but unclear if they appeared identical

Incomplete outcome data (attrition bias)
All outcomes

Low risk

From the 80 patients 3 were withdrawn. All the remaining 77 patients were included in efficacy analyses.

Selective reporting (reporting bias)

Low risk

All outcomes from Methods section reported in Results section

Size

High risk

Fewer than 50 participants per arm of the study (40 propacetamol, 40 morphine)

Wininger 2010

Methods

2 regimens of IV paracetamol (every 4 h versus every 6 h) versus 2 same regimens of placebo. Participants after abdominal laparoscopy, who present with pain. 24‐h assessment.

Participants

Type of surgery: abdominal laparoscopy

Paracetamol 1000 mg group

Entered/completing: 92/88

Age (mean, SD): 45.3 ± 12.26

Sex (male, %): 20

Placebo group 100 ml

Entered/completing: 43/37

Age (mean, SD): 46.0 ± 11.70

Sex (male, %): 14

Placebo group 65 ml

Entered/completing: 67/62

Age (mean, SD): 46.5 ± 13.08

Sex (male, %): 20

Interventions

All interventions administered on postoperative day 1

Paracetamol 1000 mg in 100 ml 15‐min IV infusion, every 6 h (total 4 doses over 24 h)

Paracetamol 650 mg in 65 ml 15‐min IV infusion, every 4 h (total of 6 doses over 24 h, not included in our analysis)

Placebo: 100 ml 15‐min IV infusion, every 6 h (total 4 doses over 24 h)

Placebo: 65 ml 15‐min IV infusion, every 4 h (total of 6 doses over 24 h)

Outcomes

Primary: SPID 0 to 24 h of acetaminophen 1000 mg versus combined placebo

Secondary:

SPID24 for acetaminophen 650 mg versus placebos (not included in our analysis)

TOTPAR24

Pain intensity at baseline, and 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 14, 16, 18, 20, 22, and 24 h

Adverse events

Vital signs

CBC, Liver Function Tests

Source of funding

Cadence Pharmaceuticals

Were treatment groups comparable at baseline?

Yes: age, sex, race, height, weight. No clinically relevant differences observed between the placebo and intravenous acetaminophen groups with regard to type of primary abdominal laparoscopic surgery, additional procedures performed, the duration of surgery, or the time from end of surgery to T0.

Details of preoperative pain

Exclusion: having a chronic pain condition, or use of opioids or tramadol daily for > 7 days immediately before study medication administration

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomization by performed by kit randomization, but there was an error (all first 109 participants allocated to either 1000 mg paracetamol or 65 ml placebo group)

Allocation concealment (selection bias)

Unclear risk

No details

Blinding (performance bias and detection bias)
All outcomes

Low risk

Blinding procedures seem adequate. Active drug and placebo solution, bottles, and labels were identical in appearance.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Outcomes seem complete. Dropouts completely described and similar between groups. WOCF imputation used for observations recorded after first request for analgesia. BOCF for observations before first request.

Selective reporting (reporting bias)

Low risk

All outcomes reported

Protocol published on clinicaltrials.gov. All outcomes from protocol reported as planned. SPID 4 & 6, TOTPAR 4 & 6, time to rescue, rescue requirements all reported despite not being mentioned on clinicaltrials.gov.

Size

Unclear risk

50 to 199 participants per arm of the study (92 paracetamol, 43 placebo, 67 placebo)

Zhou 2001

Methods

Randomized, double‐blinded, double‐dummy, placebo‐ and active‐controlled

Medication administered on postoperative day 1 when baseline pain reached moderate‐to‐severe intensity

Participants

Type of surgery: orthopedic

Propacetamol group

Entered/completing: 60/57

Age (mean, SD): 61.4 ± 12.0

Sex (male, %): 37

Ketorolac group

Entered/completing: 28/27

Age (mean, SD): 60.6 ± 11.1

Sex (male, %): 22

Placebo group

Entered/completing: 55/52

Age (mean, SD): 60.9 ± 12.4

Sex (male, %): 40

Interventions

Intervention: 2 g propacetamol over 15 min

Control: 15 mg ketorolac (not included in our analysis)

Control: 30 mg ketorolac

Placebo: saline

Outcomes

Time to onset of and number of patients experiencing analgesia (double‐stopwatch method)

Pain intensity at rest and with activity (VRS, VAS) and derived summary measures

Pain relief (categorical) and derived summary measures

Time to, number of patients requesting, and consumption of rescue medication (morphine via PCA)

Global evaluation (categorical)

Source of funding

Supported in part by a grant from UPSA Inc., France, and in part by the White Mountain Institute (a non–for profit public charity) in Los Altos, CA

Were treatment groups comparable at baseline?

Yes: demographic, anesthetic and surgical characteristics

Details of preoperative pain

Not reported

Notes

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated schedule

Allocation concealment (selection bias)

Unclear risk

Not described

Blinding (performance bias and detection bias)
All outcomes

Low risk

All study medication solutions prepared by a hospital pharmacist who was not involved in the data collection. Double‐dummy technique employed.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Although 172 patients were initially randomized into the study groups, 164 received the study medication and were included in the intention‐to‐treat analysis

Selective reporting (reporting bias)

Low risk

Free of selective reporting. All outcomes from Methods section reported in Results section.

Size

Unclear risk

50 to 199 participants per arm of the study (60 propacetamol, 28 ketorolac, 55 placebo)

AE = adverse event; ASA = American Society of Anesthesiologists physical status classification system; AUC = area under the curve; BMI: body mass index; BOCF = baseline observation carried forward; BP = blood pressure; DSST = digit symbol substitution test; h = hour; HR = heart rate; ICU = intensive care unit; IM = intramuscular; INR = international normalized ratio; IQR = interquartile range; ITT = intention‐to‐treat; IV = intravenous; LA = local anesthetic; LOCF = last observation carried forward; min = minutes; NRS = numerical rating scale; NS = normal saline; N/V = nausea/vomiting; OR = operating room; PACU = post anesthesia care unit; PCA = patient‐controlled analgesia; PI = pain intensity; PT = prothrombin time; SD = standard deviation; SPID = summed pain intensity difference; TDT = Trieger dot test; THA = total hip arthroplasty; TOTPAR = total pain relief; VAS = visual analog scale; VPS = verbal pain score; VRS = verbal rating scale; WOCF = worst observation carried forward.

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Alhashemi 2006

Pain not patient‐reported

Alhashemi 2007

Pain not patient‐reported

Alimian 2014

Paracetamol administered via continuous infusion

Anand 2013

Outcomes assessed over 75 minutes only

Ang 1990

Propacetamol administered intramuscularly

Ashrafnejad 2012

Available as abstract only with no usable data

Aydogan 2008

No pain or analgesic outcome

Caliskan 2013

Preoperative administration of interventions

Candiotti 2010

Not all participants had postoperative pain, efficacy outcomes were assessed at 24 hour intervals, not clear when drugs were administered

Cok 2011

Preemptive administration of interventions

Dowling 2014

Appears that control group did not receive placebo. Pain data only presented up to 1 hour.

Elseify 2011

First dose received after induction of anesthesia, no 4‐ or 6‐hour pain data

Fijalkowska 2006

Compares laparotomy to laparoscopy

Fourcade 2005

No data provided on 4‐ or 6‐hour intervals

Garcia 1999

Participants received propacetamol 30 minutes before operation

Gehling 2010

Paracetamol administered via continuous infusion and no data at 4 or 6 hours

Ghaffaripour 2012

Available as abstract only with no usable data

Gousheh 2013

Interventions administered 10 minutes after induction of anesthesia. Operations were at least 1 hour long; therefore administration > 30 minutes before end of surgery.

Granry 1997

Multiple dose study without data for first dose

Grundmann 2006

Study drug administered more than 30 minutes before the end of surgery

Hernandez Palazon 2001

No data provided for either 4‐ or 6‐hour intervals

Irct2012062410102N

All patients initially receive IV paracetamol

Ko 2010

Preoperative administration of interventions

Kocum 2013

Pain not patient‐reported, unclear if interventions within 30 minutes of end of surgery

Memis 2010

Multiple dose study without data for first dose

Murat 2005

Some pain assessments investigator‐reported. Unable to ascertain numbers of participants self reporting pain.

NCT01691690

Pain not patient‐reported

NCT01721486

Pain not patient‐reported

Nikoda 2006

Not randomized

Olonisakin 2012

No data beyond 3 h

Pernia 2000

Received paracetamol in both arms to evaluate efficacy of drug metamizol

Rashwan 2013

No pain data until 8 h post interventions

Silvanto 2007

Study drug administered more than 30 minutes before the end of surgery

Topal 2009

Control group did not receive active control or placebo

Toygar 2008

One control group had intervention administered before induction, and the other control group received no intervention (no placebo was administered)

Turner 2014

Interventions administered 30 minutes before surgical incision

Uvarov 2008

Control group received no intervention

Uzun 2010

Paracetamol plus placebo versus paracetamol plus metamizole, versus no treatment

Verchere 2002

Interventions administered 1 hour before the end of surgery

Zeidan 2014

Dose finding study with outcomes reported at 45 minutes

Ziolkowski 2008

All groups received paracetamol

IV: intravenous

Characteristics of studies awaiting assessment [ordered by study ID]

Atashkhoyi 2014

Methods

Not yet assessed

Participants

Interventions

Outcomes

Notes

Dawoodi 2014

Methods

Not yet assessed

Participants

Interventions

Outcomes

Notes

Jabalameli 2014

Methods

Not yet assessed

Participants

Interventions

Outcomes

Notes

Majumdar 2014

Methods

Not yet assessed

Participants

Interventions

Outcomes

Notes

Pekmezci 2014

Methods

Not yet assessed

Participants

Interventions

Outcomes

Notes

Rasheed 2007

Methods

Unclear

Participants

Unclear

Interventions

Unclear

Outcomes

Unclear

Notes

Unable to obtain full article from any source

Ritchie 2015

Methods

Not yet assessed

Participants

Interventions

Outcomes

Notes

Singla 2015

Methods

Not yet assessed

Participants

Interventions

Outcomes

Notes

Data and analyses

Open in table viewer
Comparison 1. Number of participants with > 50% pain relief over 4 hours

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

11

1149

Risk Ratio (M‐H, Fixed, 95% CI)

2.53 [2.01, 3.19]

Analysis 1.1

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

5

393

Risk Ratio (M‐H, Fixed, 95% CI)

4.80 [2.30, 10.00]

1.2 Propacetamol vs placebo

8

756

Risk Ratio (M‐H, Fixed, 95% CI)

2.19 [1.74, 2.77]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

5

353

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.86, 1.18]

Analysis 1.2

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

2

130

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.72, 1.13]

2.2 Propacetamol vs NSAIDs

3

223

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.86, 1.34]

3 Propacetamol vs opioids Show forest plot

1

61

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.85, 1.59]

Analysis 1.3

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 3 Propacetamol vs opioids.

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 3 Propacetamol vs opioids.

4 Paracetamol vs propacetamol Show forest plot

3

361

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.77, 1.24]

Analysis 1.4

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 4 Paracetamol vs propacetamol.

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 4 Paracetamol vs propacetamol.

Open in table viewer
Comparison 2. Number of participants with > 50% pain relief over 6 hours

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

10

1143

Risk Ratio (M‐H, Fixed, 95% CI)

2.86 [2.10, 3.91]

Analysis 2.1

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

6

532

Risk Ratio (M‐H, Fixed, 95% CI)

3.65 [2.15, 6.21]

1.2 Propacetamol vs placebo

6

611

Risk Ratio (M‐H, Fixed, 95% CI)

2.40 [1.64, 3.50]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

5

355

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.66, 0.95]

Analysis 2.2

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

3

212

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.66, 1.02]

2.2 Propacetamol vs NSAIDs

2

143

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.56, 1.02]

3 Propacetamol vs opioids Show forest plot

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.83, 1.09]

Analysis 2.3

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 3 Propacetamol vs opioids.

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 3 Propacetamol vs opioids.

4 Paracetamol vs propacetamol Show forest plot

3

361

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.73, 1.20]

Analysis 2.4

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 4 Paracetamol vs propacetamol.

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 4 Paracetamol vs propacetamol.

Open in table viewer
Comparison 3. Pain intensity at 4 h

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol vs placebo Show forest plot

6

485

Mean Difference (IV, Fixed, 95% CI)

‐1.21 [‐3.73, 1.31]

Analysis 3.1

Comparison 3 Pain intensity at 4 h, Outcome 1 Paracetamol vs placebo.

Comparison 3 Pain intensity at 4 h, Outcome 1 Paracetamol vs placebo.

2 Paracetamol vs NSAIDs Show forest plot

6

350

Mean Difference (IV, Fixed, 95% CI)

5.02 [3.18, 6.86]

Analysis 3.2

Comparison 3 Pain intensity at 4 h, Outcome 2 Paracetamol vs NSAIDs.

Comparison 3 Pain intensity at 4 h, Outcome 2 Paracetamol vs NSAIDs.

3 Paracetamol vs opioids

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Paracetamol vs ketamine Show forest plot

1

80

Mean Difference (IV, Fixed, 95% CI)

‐12.0 [‐19.23, ‐4.77]

Analysis 3.4

Comparison 3 Pain intensity at 4 h, Outcome 4 Paracetamol vs ketamine.

Comparison 3 Pain intensity at 4 h, Outcome 4 Paracetamol vs ketamine.

Open in table viewer
Comparison 4. Pain intensity at 6 h

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol vs placebo Show forest plot

12

837

Mean Difference (IV, Fixed, 95% CI)

‐7.48 [‐8.98, ‐5.97]

Analysis 4.1

Comparison 4 Pain intensity at 6 h, Outcome 1 Paracetamol vs placebo.

Comparison 4 Pain intensity at 6 h, Outcome 1 Paracetamol vs placebo.

2 Paracetamol vs NSAIDs Show forest plot

9

524

Mean Difference (IV, Fixed, 95% CI)

2.95 [1.18, 4.72]

Analysis 4.2

Comparison 4 Pain intensity at 6 h, Outcome 2 Paracetamol vs NSAIDs.

Comparison 4 Pain intensity at 6 h, Outcome 2 Paracetamol vs NSAIDs.

3 Paracetamol vs opioids Show forest plot

1

50

Mean Difference (IV, Fixed, 95% CI)

3.0 [‐1.57, 7.57]

Analysis 4.3

Comparison 4 Pain intensity at 6 h, Outcome 3 Paracetamol vs opioids.

Comparison 4 Pain intensity at 6 h, Outcome 3 Paracetamol vs opioids.

4 Paracetamol vs ketamine Show forest plot

1

80

Mean Difference (IV, Fixed, 95% CI)

‐13.0 [‐18.28, ‐7.72]

Analysis 4.4

Comparison 4 Pain intensity at 6 h, Outcome 4 Paracetamol vs ketamine.

Comparison 4 Pain intensity at 6 h, Outcome 4 Paracetamol vs ketamine.

Open in table viewer
Comparison 5. Number of participants requiring rescue medication

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

9

859

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.64, 0.77]

Analysis 5.1

Comparison 5 Number of participants requiring rescue medication, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 5 Number of participants requiring rescue medication, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

6

655

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.69, 0.82]

1.2 Propacetamol vs placebo

3

204

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.35, 0.69]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

5

309

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.87, 1.63]

Analysis 5.2

Comparison 5 Number of participants requiring rescue medication, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 5 Number of participants requiring rescue medication, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

2

120

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.59, 1.98]

2.2 Propacetamol vs NSAIDs

3

189

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.86, 1.77]

3 Propacetamol vs opioids Show forest plot

2

139

Risk Ratio (M‐H, Fixed, 95% CI)

1.83 [0.72, 4.64]

Analysis 5.3

Comparison 5 Number of participants requiring rescue medication, Outcome 3 Propacetamol vs opioids.

Comparison 5 Number of participants requiring rescue medication, Outcome 3 Propacetamol vs opioids.

4 Paracetamol vs propacetamol Show forest plot

1

161

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [0.82, 2.17]

Analysis 5.4

Comparison 5 Number of participants requiring rescue medication, Outcome 4 Paracetamol vs propacetamol.

Comparison 5 Number of participants requiring rescue medication, Outcome 4 Paracetamol vs propacetamol.

Open in table viewer
Comparison 6. Time to rescue medication (minutes)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

9

839

Mean Difference (IV, Fixed, 95% CI)

6.43 [4.54, 8.32]

Analysis 6.1

Comparison 6 Time to rescue medication (minutes), Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 6 Time to rescue medication (minutes), Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

6

523

Mean Difference (IV, Fixed, 95% CI)

5.78 [3.86, 7.71]

1.2 Propacetamol vs placebo

3

316

Mean Difference (IV, Fixed, 95% CI)

23.72 [13.79, 33.65]

2 Paracetamol vs NSAIDs Show forest plot

2

138

Mean Difference (IV, Fixed, 95% CI)

‐1.14 [‐36.21, 33.92]

Analysis 6.2

Comparison 6 Time to rescue medication (minutes), Outcome 2 Paracetamol vs NSAIDs.

Comparison 6 Time to rescue medication (minutes), Outcome 2 Paracetamol vs NSAIDs.

Open in table viewer
Comparison 7. Opioid consumption (IV morphine equivalents) over 4 hours

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

6

255

Mean Difference (IV, Fixed, 95% CI)

‐1.42 [‐1.81, ‐1.03]

Analysis 7.1

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

4

141

Mean Difference (IV, Fixed, 95% CI)

‐1.33 [‐1.75, ‐0.91]

1.2 Propacetamol vs placebo

2

114

Mean Difference (IV, Fixed, 95% CI)

‐2.05 [‐3.15, ‐0.95]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

3

294

Mean Difference (IV, Fixed, 95% CI)

‐0.19 [‐0.37, ‐0.02]

Analysis 7.2

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

2

118

Mean Difference (IV, Fixed, 95% CI)

0.28 [‐1.04, 1.59]

2.2 Propacetamol vs NSAIDs

1

176

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐0.38, ‐0.02]

3 Propacetamol vs opioids Show forest plot

1

80

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐3.09, 1.09]

Analysis 7.3

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 3 Propacetamol vs opioids.

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 3 Propacetamol vs opioids.

Open in table viewer
Comparison 8. Opioid consumption (IV morphine equivalents) over 6 hours

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

13

777

Mean Difference (IV, Fixed, 95% CI)

‐1.92 [‐2.41, ‐1.42]

Analysis 8.1

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

8

404

Mean Difference (IV, Fixed, 95% CI)

‐1.83 [‐2.35, ‐1.31]

1.2 Propacetamol vs placebo

6

373

Mean Difference (IV, Fixed, 95% CI)

‐2.67 [‐4.21, ‐1.13]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

8

540

Mean Difference (IV, Fixed, 95% CI)

‐0.12 [‐0.37, 0.12]

Analysis 8.2

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

3

160

Mean Difference (IV, Fixed, 95% CI)

0.81 [‐0.87, 2.49]

2.2 Propacetamol vs NSAIDs

5

380

Mean Difference (IV, Fixed, 95% CI)

‐0.14 [‐0.39, 0.11]

3 Propacetamol vs opioids Show forest plot

1

80

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐3.01, 2.01]

Analysis 8.3

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 3 Propacetamol vs opioids.

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 3 Propacetamol vs opioids.

4 Paracetamol vs propacetamol Show forest plot

1

98

Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐4.15, 3.35]

Analysis 8.4

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 4 Paracetamol vs propacetamol.

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 4 Paracetamol vs propacetamol.

Open in table viewer
Comparison 9. Global evaluation rated as good/satisfied or excellent/very satisfied

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

16

2015

Risk Ratio (M‐H, Fixed, 95% CI)

1.34 [1.25, 1.43]

Analysis 9.1

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

9

876

Risk Ratio (M‐H, Fixed, 95% CI)

1.45 [1.31, 1.60]

1.2 Propacetamol vs placebo

9

1139

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [1.16, 1.37]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

11

795

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.87, 1.00]

Analysis 9.2

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

6

247

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.91, 1.04]

2.2 Propacetamol vs NSAIDs

5

548

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.82, 1.01]

3 Propacetamol vs opioids Show forest plot

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.81, 1.23]

Analysis 9.3

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 3 Propacetamol vs opioids.

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 3 Propacetamol vs opioids.

3.1 Propacetamol

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.81, 1.23]

4 Paracetamol vs propacetamol Show forest plot

2

263

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.83, 1.15]

Analysis 9.4

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 4 Paracetamol vs propacetamol.

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 4 Paracetamol vs propacetamol.

Open in table viewer
Comparison 10. Global evaluation using a numerical rating scale (0 to 10)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

3

342

Mean Difference (IV, Fixed, 95% CI)

0.35 [0.04, 0.66]

Analysis 10.1

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.46, 0.26]

1.2 Propacetamol vs placebo

2

282

Mean Difference (IV, Fixed, 95% CI)

1.64 [1.04, 2.25]

2 Paracetamol vs NSAIDs Show forest plot

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.63, 0.03]

Analysis 10.2

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 2 Paracetamol vs NSAIDs.

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 2 Paracetamol vs NSAIDs.

3 Propacetamol vs opioids Show forest plot

2

141

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐0.18, 0.98]

Analysis 10.3

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 3 Propacetamol vs opioids.

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 3 Propacetamol vs opioids.

Open in table viewer
Comparison 11. Number of participants with adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

20

2359

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [1.01, 1.22]

Analysis 11.1

Comparison 11 Number of participants with adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 11 Number of participants with adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

12

950

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.93, 1.19]

1.2 Propacetamol vs placebo

10

1409

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [1.02, 1.35]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

6

471

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.72, 1.32]

Analysis 11.2

Comparison 11 Number of participants with adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 11 Number of participants with adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

3

248

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.66, 1.68]

2.2 Propacetamol vs NSAIDs

3

223

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.62, 1.37]

3 Propacetamol vs opioids Show forest plot

1

61

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.29, 1.23]

Analysis 11.3

Comparison 11 Number of participants with adverse events, Outcome 3 Propacetamol vs opioids.

Comparison 11 Number of participants with adverse events, Outcome 3 Propacetamol vs opioids.

Open in table viewer
Comparison 12. Number of participants with serious adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

10

970

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.19, 6.59]

Analysis 12.1

Comparison 12 Number of participants with serious adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 12 Number of participants with serious adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

6

634

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.19, 6.59]

1.2 Propacetamol vs placebo

5

336

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

9

798

Risk Ratio (M‐H, Fixed, 95% CI)

0.43 [0.11, 1.65]

Analysis 12.2

Comparison 12 Number of participants with serious adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 12 Number of participants with serious adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

4

270

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.07, 15.26]

2.2 Propacetamol vs NSAIDs

5

528

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.07, 1.65]

3 Paracetamol or propacetamol vs opioids Show forest plot

3

191

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 71.51]

Analysis 12.3

Comparison 12 Number of participants with serious adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.

Comparison 12 Number of participants with serious adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.

3.1 Paracetamol vs opioids

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Propacetamol vs opioids

2

141

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 71.51]

Open in table viewer
Comparison 13. Number of participants withdrawing due to adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

37

2654

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [0.56, 2.84]

Analysis 13.1

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

27

1912

Risk Ratio (M‐H, Fixed, 95% CI)

1.25 [0.49, 3.17]

1.2 Propacetamol vs placebo

12

742

Risk Ratio (M‐H, Fixed, 95% CI)

1.29 [0.25, 6.68]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

24

1429

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.42, 3.12]

Analysis 13.2

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

19

1029

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.31, 3.22]

2.2 Propacetamol vs NSAIDs

5

400

Risk Ratio (M‐H, Fixed, 95% CI)

1.67 [0.22, 12.37]

3 Paracetamol or propacetamol vs opioids Show forest plot

6

505

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.95]

Analysis 13.3

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.

3.1 Paracetamol vs opioids

2

254

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Propacetamol vs opioids

4

251

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.95]

4 Paracetamol vs ketamine Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Analysis 13.4

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 4 Paracetamol vs ketamine.

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 4 Paracetamol vs ketamine.

Open in table viewer
Comparison 14. Number of participants withdrawing due to lack of efficacy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

38

2600

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.38, 0.79]

Analysis 14.1

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 1 Paracetamol or propacetamol vs placebo.

1.1 Paracetamol vs placebo

26

1711

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.10, 2.78]

1.2 Propacetamol vs placebo

14

889

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.38, 0.80]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

24

1393

Risk Ratio (M‐H, Fixed, 95% CI)

1.30 [0.81, 2.08]

Analysis 14.2

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

2.1 Paracetamol vs NSAIDs

18

934

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 71.89]

2.2 Propacetamol vs NSAIDs

6

459

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [0.78, 2.03]

3 Paracetamol or propacetamol vs opioids Show forest plot

6

505

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.25, 100.97]

Analysis 14.3

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 3 Paracetamol or propacetamol vs opioids.

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 3 Paracetamol or propacetamol vs opioids.

3.1 Paracetamol vs opioids

2

254

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Propacetamol vs opioids

4

251

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.25, 100.97]

4 Paracetamol vs ketamine Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Analysis 14.4

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 4 Paracetamol vs ketamine.

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 4 Paracetamol vs ketamine.

Open in table viewer
Comparison 15. Number of participants with pain on infusion

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol vs placebo Show forest plot

3

467

Risk Ratio (M‐H, Fixed, 95% CI)

3.05 [0.80, 11.54]

Analysis 15.1

Comparison 15 Number of participants with pain on infusion, Outcome 1 Paracetamol vs placebo.

Comparison 15 Number of participants with pain on infusion, Outcome 1 Paracetamol vs placebo.

2 Propacetamol vs placebo Show forest plot

6

645

Risk Ratio (M‐H, Fixed, 95% CI)

13.07 [5.35, 31.98]

Analysis 15.2

Comparison 15 Number of participants with pain on infusion, Outcome 2 Propacetamol vs placebo.

Comparison 15 Number of participants with pain on infusion, Outcome 2 Propacetamol vs placebo.

3 Propacetamol vs paracetamol Show forest plot

3

362

Risk Ratio (M‐H, Fixed, 95% CI)

8.31 [4.20, 16.46]

Analysis 15.3

Comparison 15 Number of participants with pain on infusion, Outcome 3 Propacetamol vs paracetamol.

Comparison 15 Number of participants with pain on infusion, Outcome 3 Propacetamol vs paracetamol.

Open in table viewer
Comparison 16. Individual adverse events: paracetamol or propacetamol vs placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Nausea Show forest plot

15

1267

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.73, 0.98]

Analysis 16.1

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 1 Nausea.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 1 Nausea.

1.1 Paracetamol vs placebo

13

1037

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.66, 0.90]

1.2 Propacetamol vs placebo

3

230

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [0.98, 2.69]

2 Vomiting Show forest plot

15

1414

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.57, 0.87]

Analysis 16.2

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 2 Vomiting.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 2 Vomiting.

2.1 Paracetamol vs placebo

13

1037

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.51, 0.80]

2.2 Propacetamol vs placebo

3

377

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [0.75, 3.48]

3 Nausea/vomiting Show forest plot

10

1064

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.74, 1.08]

Analysis 16.3

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 3 Nausea/vomiting.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 3 Nausea/vomiting.

3.1 Paracetamol vs placebo

4

191

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.57, 1.70]

3.2 Propacetamol vs placebo

6

873

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.72, 1.08]

4 Pruritus Show forest plot

7

618

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.60, 1.40]

Analysis 16.4

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 4 Pruritus.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 4 Pruritus.

4.1 Paracetamol vs placebo

5

320

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.64, 1.72]

4.2 Propacetamol vs placebo

3

298

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.29, 1.51]

5 Respiratory depression Show forest plot

11

1082

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.31, 1.92]

Analysis 16.5

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 5 Respiratory depression.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 5 Respiratory depression.

5.1 Paracetamol vs placebo

6

363

Risk Ratio (M‐H, Fixed, 95% CI)

0.28 [0.03, 2.65]

5.2 Propacetamol vs placebo

5

719

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.35, 2.80]

6 Sedation Show forest plot

10

566

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.66, 1.51]

Analysis 16.6

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 6 Sedation.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 6 Sedation.

6.1 Paracetamol vs placebo

6

341

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.42, 2.01]

6.2 Propacetamol vs placebo

4

225

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.65, 1.69]

7 Urinary retention Show forest plot

8

1050

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.68, 1.66]

Analysis 16.7

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 7 Urinary retention.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 7 Urinary retention.

7.1 Paracetamol vs placebo

5

373

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [0.28, 6.66]

7.2 Propacetamol vs placebo

3

677

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.65, 1.66]

8 Allergy/skin rash/local reaction Show forest plot

7

1131

Risk Ratio (M‐H, Fixed, 95% CI)

1.54 [0.61, 3.91]

Analysis 16.8

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 8 Allergy/skin rash/local reaction.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 8 Allergy/skin rash/local reaction.

8.1 Paracetamol vs placebo

4

370

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.24, 4.34]

8.2 Propacetamol vs placebo

4

761

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [0.57, 6.73]

Open in table viewer
Comparison 17. Individual adverse events: paracetamol or propacetamol vs NSAIDs

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Nausea Show forest plot

11

856

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.90, 1.28]

Analysis 17.1

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 1 Nausea.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 1 Nausea.

1.1 Paracetamol vs NSAIDs

8

424

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.31]

1.2 Propacetamol vs NSAIDs

3

432

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.92, 1.44]

2 Vomiting Show forest plot

11

856

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.89, 1.55]

Analysis 17.2

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 2 Vomiting.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 2 Vomiting.

2.1 Paracetamol vs NSAIDs

8

424

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.77, 1.68]

2.2 Propacetamol vs NSAIDs

3

432

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [0.81, 1.81]

3 Nausea/vomiting Show forest plot

8

408

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.62, 1.97]

Analysis 17.3

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 3 Nausea/vomiting.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 3 Nausea/vomiting.

3.1 Paracetamol vs NSAIDs

4

208

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.42, 2.39]

3.2 Propacetamol vs NSAIDs

4

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.2 [0.55, 2.60]

4 Pruritus Show forest plot

8

558

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.69, 1.34]

Analysis 17.4

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 4 Pruritus.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 4 Pruritus.

4.1 Paracetamol vs NSAIDs

5

286

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.75, 1.51]

4.2 Propacetamol vs NSAIDs

3

272

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.37, 1.60]

5 Respiratory depression Show forest plot

9

510

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.17, 3.26]

Analysis 17.5

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 5 Respiratory depression.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 5 Respiratory depression.

5.1 Paracetamol vs NSAIDs

8

470

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.17, 3.26]

5.2 Propacetamol vs NSAIDs

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Sedation Show forest plot

6

278

Risk Ratio (M‐H, Fixed, 95% CI)

2.6 [0.63, 10.75]

Analysis 17.6

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 6 Sedation.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 6 Sedation.

6.1 Paracetamol vs NSAIDs

4

208

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.07, 14.90]

6.2 Propacetamol vs NSAIDs

2

70

Risk Ratio (M‐H, Fixed, 95% CI)

3.67 [0.63, 21.22]

7 Urinary retention Show forest plot

6

390

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.51, 2.32]

Analysis 17.7

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 7 Urinary retention.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 7 Urinary retention.

7.1 Paracetamol vs NSAIDs

4

178

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.24, 4.02]

7.2 Propacetamol vs NSAIDs

2

212

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.47, 2.78]

8 Allergy/skin rash/local reaction Show forest plot

8

399

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.24, 2.26]

Analysis 17.8

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 8 Allergy/skin rash/local reaction.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 8 Allergy/skin rash/local reaction.

8.1 Paracetamol vs NSAIDs

6

290

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.26, 4.02]

8.2 Propacetamol vs NSAIDs

2

109

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.04, 3.16]

Open in table viewer
Comparison 18. Individual adverse events: paracetamol or propacetamol vs opioids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Nausea Show forest plot

6

545

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.24, 0.65]

Analysis 18.1

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 1 Nausea.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 1 Nausea.

1.1 Paracetamol vs opioids

4

438

Risk Ratio (M‐H, Fixed, 95% CI)

0.31 [0.17, 0.56]

1.2 Propacetamol vs opioids

2

107

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.32, 1.91]

2 Vomiting Show forest plot

5

495

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.12, 0.72]

Analysis 18.2

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 2 Vomiting.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 2 Vomiting.

2.1 Paracetamol vs opioids

3

388

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.08, 0.71]

2.2 Propacetamol vs opioids

2

107

Risk Ratio (M‐H, Fixed, 95% CI)

0.51 [0.10, 2.62]

3 Nausea/vomiting Show forest plot

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.15, 1.64]

Analysis 18.3

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 3 Nausea/vomiting.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 3 Nausea/vomiting.

3.1 Propacetamol vs opioids

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.15, 1.64]

4 Pruritus Show forest plot

3

157

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.21, 1.43]

Analysis 18.4

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 4 Pruritus.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 4 Pruritus.

4.1 Paracetamol vs opioids

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.27, 8.22]

4.2 Propacetamol vs opioids

2

107

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.10, 1.19]

5 Respiratory depression Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Analysis 18.5

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 5 Respiratory depression.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 5 Respiratory depression.

5.1 Paracetamol vs opioids

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Sedation Show forest plot

3

354

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.03, 0.34]

Analysis 18.6

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 6 Sedation.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 6 Sedation.

6.1 Paracetamol vs opioids

3

354

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.03, 0.34]

Open in table viewer
Comparison 19. Individual adverse events: paracetamol vs ketamine

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Nausea Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.66, 1.30]

Analysis 19.1

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 1 Nausea.

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 1 Nausea.

2 Vomiting Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.22, 1.33]

Analysis 19.2

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 2 Vomiting.

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 2 Vomiting.

3 Sedation Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 71.51]

Analysis 19.3

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 3 Sedation.

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 3 Sedation.

2016 Study flow diagram.
Figuras y tablas -
Figure 1

2016 Study flow diagram.

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figuras y tablas -
Figure 2

'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.
Figuras y tablas -
Figure 3

'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study.

Forest plot of comparison: 1 Number of participants with > 50% pain relief over 4 hours, outcome: 1.1 Propacetamol or paracetamol versus placebo.
Figuras y tablas -
Figure 4

Forest plot of comparison: 1 Number of participants with > 50% pain relief over 4 hours, outcome: 1.1 Propacetamol or paracetamol versus placebo.

Forest plot of comparison: 2 Number of participants with > 50% pain relief over 6 hours, outcome: 2.1 Propacetamol or paracetamol versus placebo.
Figuras y tablas -
Figure 5

Forest plot of comparison: 2 Number of participants with > 50% pain relief over 6 hours, outcome: 2.1 Propacetamol or paracetamol versus placebo.

Forest plot of comparison: 15 Pain on infusion, outcome: 15.3 Propacetamol versus paracetamol.
Figuras y tablas -
Figure 6

Forest plot of comparison: 15 Pain on infusion, outcome: 15.3 Propacetamol versus paracetamol.

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 1.1

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 1.2

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 3 Propacetamol vs opioids.
Figuras y tablas -
Analysis 1.3

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 3 Propacetamol vs opioids.

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 4 Paracetamol vs propacetamol.
Figuras y tablas -
Analysis 1.4

Comparison 1 Number of participants with > 50% pain relief over 4 hours, Outcome 4 Paracetamol vs propacetamol.

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 2.1

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 2.2

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 3 Propacetamol vs opioids.
Figuras y tablas -
Analysis 2.3

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 3 Propacetamol vs opioids.

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 4 Paracetamol vs propacetamol.
Figuras y tablas -
Analysis 2.4

Comparison 2 Number of participants with > 50% pain relief over 6 hours, Outcome 4 Paracetamol vs propacetamol.

Comparison 3 Pain intensity at 4 h, Outcome 1 Paracetamol vs placebo.
Figuras y tablas -
Analysis 3.1

Comparison 3 Pain intensity at 4 h, Outcome 1 Paracetamol vs placebo.

Comparison 3 Pain intensity at 4 h, Outcome 2 Paracetamol vs NSAIDs.
Figuras y tablas -
Analysis 3.2

Comparison 3 Pain intensity at 4 h, Outcome 2 Paracetamol vs NSAIDs.

Comparison 3 Pain intensity at 4 h, Outcome 4 Paracetamol vs ketamine.
Figuras y tablas -
Analysis 3.4

Comparison 3 Pain intensity at 4 h, Outcome 4 Paracetamol vs ketamine.

Comparison 4 Pain intensity at 6 h, Outcome 1 Paracetamol vs placebo.
Figuras y tablas -
Analysis 4.1

Comparison 4 Pain intensity at 6 h, Outcome 1 Paracetamol vs placebo.

Comparison 4 Pain intensity at 6 h, Outcome 2 Paracetamol vs NSAIDs.
Figuras y tablas -
Analysis 4.2

Comparison 4 Pain intensity at 6 h, Outcome 2 Paracetamol vs NSAIDs.

Comparison 4 Pain intensity at 6 h, Outcome 3 Paracetamol vs opioids.
Figuras y tablas -
Analysis 4.3

Comparison 4 Pain intensity at 6 h, Outcome 3 Paracetamol vs opioids.

Comparison 4 Pain intensity at 6 h, Outcome 4 Paracetamol vs ketamine.
Figuras y tablas -
Analysis 4.4

Comparison 4 Pain intensity at 6 h, Outcome 4 Paracetamol vs ketamine.

Comparison 5 Number of participants requiring rescue medication, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 5.1

Comparison 5 Number of participants requiring rescue medication, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 5 Number of participants requiring rescue medication, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 5.2

Comparison 5 Number of participants requiring rescue medication, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 5 Number of participants requiring rescue medication, Outcome 3 Propacetamol vs opioids.
Figuras y tablas -
Analysis 5.3

Comparison 5 Number of participants requiring rescue medication, Outcome 3 Propacetamol vs opioids.

Comparison 5 Number of participants requiring rescue medication, Outcome 4 Paracetamol vs propacetamol.
Figuras y tablas -
Analysis 5.4

Comparison 5 Number of participants requiring rescue medication, Outcome 4 Paracetamol vs propacetamol.

Comparison 6 Time to rescue medication (minutes), Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 6.1

Comparison 6 Time to rescue medication (minutes), Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 6 Time to rescue medication (minutes), Outcome 2 Paracetamol vs NSAIDs.
Figuras y tablas -
Analysis 6.2

Comparison 6 Time to rescue medication (minutes), Outcome 2 Paracetamol vs NSAIDs.

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 7.1

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 7.2

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 3 Propacetamol vs opioids.
Figuras y tablas -
Analysis 7.3

Comparison 7 Opioid consumption (IV morphine equivalents) over 4 hours, Outcome 3 Propacetamol vs opioids.

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 8.1

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 8.2

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 3 Propacetamol vs opioids.
Figuras y tablas -
Analysis 8.3

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 3 Propacetamol vs opioids.

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 4 Paracetamol vs propacetamol.
Figuras y tablas -
Analysis 8.4

Comparison 8 Opioid consumption (IV morphine equivalents) over 6 hours, Outcome 4 Paracetamol vs propacetamol.

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 9.1

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 9.2

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 3 Propacetamol vs opioids.
Figuras y tablas -
Analysis 9.3

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 3 Propacetamol vs opioids.

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 4 Paracetamol vs propacetamol.
Figuras y tablas -
Analysis 9.4

Comparison 9 Global evaluation rated as good/satisfied or excellent/very satisfied, Outcome 4 Paracetamol vs propacetamol.

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 10.1

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 2 Paracetamol vs NSAIDs.
Figuras y tablas -
Analysis 10.2

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 2 Paracetamol vs NSAIDs.

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 3 Propacetamol vs opioids.
Figuras y tablas -
Analysis 10.3

Comparison 10 Global evaluation using a numerical rating scale (0 to 10), Outcome 3 Propacetamol vs opioids.

Comparison 11 Number of participants with adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 11.1

Comparison 11 Number of participants with adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 11 Number of participants with adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 11.2

Comparison 11 Number of participants with adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 11 Number of participants with adverse events, Outcome 3 Propacetamol vs opioids.
Figuras y tablas -
Analysis 11.3

Comparison 11 Number of participants with adverse events, Outcome 3 Propacetamol vs opioids.

Comparison 12 Number of participants with serious adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 12.1

Comparison 12 Number of participants with serious adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 12 Number of participants with serious adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 12.2

Comparison 12 Number of participants with serious adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 12 Number of participants with serious adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.
Figuras y tablas -
Analysis 12.3

Comparison 12 Number of participants with serious adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 13.1

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 13.2

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.
Figuras y tablas -
Analysis 13.3

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 3 Paracetamol or propacetamol vs opioids.

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 4 Paracetamol vs ketamine.
Figuras y tablas -
Analysis 13.4

Comparison 13 Number of participants withdrawing due to adverse events, Outcome 4 Paracetamol vs ketamine.

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 1 Paracetamol or propacetamol vs placebo.
Figuras y tablas -
Analysis 14.1

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 1 Paracetamol or propacetamol vs placebo.

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 2 Paracetamol or propacetamol vs NSAIDs.
Figuras y tablas -
Analysis 14.2

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 2 Paracetamol or propacetamol vs NSAIDs.

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 3 Paracetamol or propacetamol vs opioids.
Figuras y tablas -
Analysis 14.3

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 3 Paracetamol or propacetamol vs opioids.

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 4 Paracetamol vs ketamine.
Figuras y tablas -
Analysis 14.4

Comparison 14 Number of participants withdrawing due to lack of efficacy, Outcome 4 Paracetamol vs ketamine.

Comparison 15 Number of participants with pain on infusion, Outcome 1 Paracetamol vs placebo.
Figuras y tablas -
Analysis 15.1

Comparison 15 Number of participants with pain on infusion, Outcome 1 Paracetamol vs placebo.

Comparison 15 Number of participants with pain on infusion, Outcome 2 Propacetamol vs placebo.
Figuras y tablas -
Analysis 15.2

Comparison 15 Number of participants with pain on infusion, Outcome 2 Propacetamol vs placebo.

Comparison 15 Number of participants with pain on infusion, Outcome 3 Propacetamol vs paracetamol.
Figuras y tablas -
Analysis 15.3

Comparison 15 Number of participants with pain on infusion, Outcome 3 Propacetamol vs paracetamol.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 1 Nausea.
Figuras y tablas -
Analysis 16.1

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 1 Nausea.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 2 Vomiting.
Figuras y tablas -
Analysis 16.2

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 2 Vomiting.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 3 Nausea/vomiting.
Figuras y tablas -
Analysis 16.3

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 3 Nausea/vomiting.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 4 Pruritus.
Figuras y tablas -
Analysis 16.4

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 4 Pruritus.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 5 Respiratory depression.
Figuras y tablas -
Analysis 16.5

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 5 Respiratory depression.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 6 Sedation.
Figuras y tablas -
Analysis 16.6

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 6 Sedation.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 7 Urinary retention.
Figuras y tablas -
Analysis 16.7

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 7 Urinary retention.

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 8 Allergy/skin rash/local reaction.
Figuras y tablas -
Analysis 16.8

Comparison 16 Individual adverse events: paracetamol or propacetamol vs placebo, Outcome 8 Allergy/skin rash/local reaction.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 1 Nausea.
Figuras y tablas -
Analysis 17.1

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 1 Nausea.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 2 Vomiting.
Figuras y tablas -
Analysis 17.2

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 2 Vomiting.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 3 Nausea/vomiting.
Figuras y tablas -
Analysis 17.3

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 3 Nausea/vomiting.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 4 Pruritus.
Figuras y tablas -
Analysis 17.4

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 4 Pruritus.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 5 Respiratory depression.
Figuras y tablas -
Analysis 17.5

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 5 Respiratory depression.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 6 Sedation.
Figuras y tablas -
Analysis 17.6

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 6 Sedation.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 7 Urinary retention.
Figuras y tablas -
Analysis 17.7

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 7 Urinary retention.

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 8 Allergy/skin rash/local reaction.
Figuras y tablas -
Analysis 17.8

Comparison 17 Individual adverse events: paracetamol or propacetamol vs NSAIDs, Outcome 8 Allergy/skin rash/local reaction.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 1 Nausea.
Figuras y tablas -
Analysis 18.1

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 1 Nausea.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 2 Vomiting.
Figuras y tablas -
Analysis 18.2

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 2 Vomiting.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 3 Nausea/vomiting.
Figuras y tablas -
Analysis 18.3

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 3 Nausea/vomiting.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 4 Pruritus.
Figuras y tablas -
Analysis 18.4

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 4 Pruritus.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 5 Respiratory depression.
Figuras y tablas -
Analysis 18.5

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 5 Respiratory depression.

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 6 Sedation.
Figuras y tablas -
Analysis 18.6

Comparison 18 Individual adverse events: paracetamol or propacetamol vs opioids, Outcome 6 Sedation.

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 1 Nausea.
Figuras y tablas -
Analysis 19.1

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 1 Nausea.

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 2 Vomiting.
Figuras y tablas -
Analysis 19.2

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 2 Vomiting.

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 3 Sedation.
Figuras y tablas -
Analysis 19.3

Comparison 19 Individual adverse events: paracetamol vs ketamine, Outcome 3 Sedation.

Summary of findings for the main comparison. Proportion of participants experiencing at least 50% of maximum pain relief at 4 hours

IV paracetamol/propacetamol compared to placebo or other analgesics for postoperative pain

Patient or population: patients with postoperative pain
Settings: hospital
Intervention: IV paracetamol/propacetamol
Comparison: placebo or other analgesics

Comparison

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Assumed risk

Corresponding risk

Placebo or other analgesics

IV paracetamol/propacetamol

Para/propacetamol vs placebo
see footnote1

156 per 1000

394 per 1000
(313 to 497)

RR 2.53
(2.01 to 3.19)

1149
(11 studies)

⊕⊕⊕⊕
high2,3

Paracetamol vs placebo
see footnote1

66 per 1000

317 per 1000
(152 to 661)

RR 4.8
(2.3 to 10)

393
(5 studies)

⊕⊕⊕⊝
moderate2,3,4

Propacetamol vs placebo
see footnote1

188 per 1000

411 per 1000
(327 to 520)

RR 2.19
(1.74 to 2.77)

756
(8 studies)

⊕⊕⊕⊝
moderate2,3,4

Para/propacetamol vs NSAIDs
see footnote1

599 per 1000

605 per 1000
(515 to 707)

RR 1.01
(0.86 to 1.18)

353
(5 studies)

⊕⊕⊝⊝
low4,5

Paracetamol vs NSAIDs
see footnote1

631 per 1000

568 per 1000
(454 to 713)

RR 0.9
(0.72 to 1.13)

130
(2 studies)

⊕⊝⊝⊝
very low4,5,6

Propacetamol vs NSAIDs
see footnote1

577 per 1000

624 per 1000
(496 to 774)

RR 1.08
(0.86 to 1.34)

223
(3 studies)

⊕⊝⊝⊝
very low2,4,5,6

Paracetamol vs propacetamol
see footnote1

428 per 1000

419 per 1000
(329 to 530)

RR 0.98
(0.77 to 1.24)

361
(3 studies)

⊕⊕⊕⊝
moderate4

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; IV: intravenous; NSAIDs: nonsteroidal anti‐inflammatory drugs; RR: risk ratio; SPID = summed pain intensity difference; TOTPAR = total pain relief; VAS: visual analog scale

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1TOTPAR or SPID using either VAS or categorical data, and calculating their corresponding percentage of theoretical maximum TOTPAR and SPID.
2Considerable unexplained heterogeneity exists between studies.
3Large effect.
4Total # events < 300.
5Different NSAIDs studied.
6Wide confidence interval that includes no effect and appreciable benefit and/or harm.

Figuras y tablas -
Summary of findings for the main comparison. Proportion of participants experiencing at least 50% of maximum pain relief at 4 hours
Summary of findings 2. Proportion of participants experiencing at least 50% of maximum pain relief at 6 hours

IV paracetamol/propacetamol compared to placebo or other analgesics for postoperative pain

Patient or population: patients with postoperative pain
Settings: hospital
Intervention: IV paracetamol/propacetamol
Comparison: placebo or other analgesics

Comparison

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Assumed risk

Corresponding risk

Placebo or other analgesics

IV paracetamol/propacetamol

Para/propacetamol vs placebo
see footnote1

97 per 1000

276 per 1000
(203 to 378)

RR 2.86
(2.1 to 3.91)

1143
(10 studies)

⊕⊕⊕⊝
moderate2,3,4

Paracetamol vs placebo
see footnote1

83 per 1000

304 per 1000
(179 to 517)

RR 3.65
(2.15 to 6.21)

532
(6 studies)

⊕⊕⊕⊝
moderate2,3,4

Propacetamol vs placebo
see footnote1

105 per 1000

252 per 1000
(172 to 367)

RR 2.4
(1.64 to 3.5)

611
(6 studies)

⊕⊕⊝⊝
low2,3,4,5,6

Para/propacetamol vs NSAIDs
see footnote1

632 per 1000

499 per 1000
(417 to 600)

RR 0.79
(0.66 to 0.95)

355
(5 studies)

⊕⊝⊝⊝
very low3,7,8

Paracetamol vs NSAIDs
see footnote1

623 per 1000

511 per 1000
(411 to 635)

RR 0.82
(0.66 to 1.02)

212
(3 studies)

⊕⊝⊝⊝
very low3,7,9,10

Propacetamol vs NSAIDs
see footnote1

649 per 1000

487 per 1000
(364 to 662)

RR 0.75
(0.56 to 1.02)

143
(2 studies)

⊕⊝⊝⊝
very low3,7,9,10

Paracetamol vs propacetamol
see footnote1

411 per 1000

386 per 1000
(300 to 493)

RR 0.94
(0.73 to 1.2)

361
(3 studies)

⊕⊕⊝⊝
low3,10

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; NNT = number needed to treat to benefit; NSAIDs: nonsteroidal anti‐inflammatory drugs; RR: risk ratio; SPID = summed pain intensity difference; TOTPAR = total pain relief; VAS: visual analog scale

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1TOTPAR or SPID using either VAS or categorical data, and calculating their corresponding percentage of theoretical maximum TOTPAR and SPID.
2Considerable unexplained heterogeneity exists between studies.
3Total # events <300.
4Large effect.
5One study data "not estimable" because of zero events in both groups.
6Publication bias favoring propacetamol; < 400 additional participants needed in studies with zero effect (relative benefit of one) required to change the NNT for at least 50% maximum pain relief to an unacceptably high level (in this case a NNT of 10).
7Different NSAIDs studied.
8Publication bias for superiority of NSAID; < 400 additional participants needed in studies with zero effect (relative benefit of one) required to change the NNT for at least 50% maximum pain relief to an unacceptably high level (in this case a NNT of 10).
9All individual studies < 100 participants.
10Wide confidence interval that includes no effect and appreciable benefit and/or harm.

Figuras y tablas -
Summary of findings 2. Proportion of participants experiencing at least 50% of maximum pain relief at 6 hours
Summary of findings 3. Mean pain intensity over a 4‐hour period

IV paracetamol compared to placebo or other analgesics for postoperative pain

Patient or population: patients with postoperative pain
Settings: hospital
Intervention: IV paracetamol
Comparison: placebo or other analgesics

Comparison

Illustrative comparative risks* (95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Paracetamol vs placebo

The mean pain intensity over a 4‐hour period was:
1.21 lower (3.73 lower to 1.31 higher)

485
(6 studies)

⊕⊕⊝⊝
low1,2

Paracetamol vs NSAIDs

The mean pain intensity over a 4‐hour period was:
5.02 higher (3.18 to 6.86 higher)

350
(6 studies)

⊕⊝⊝⊝
very low1,3,4,5,6

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; NSAIDs: nonsteroidal anti‐inflammatory drugs

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1See 'Risk of bias' tables; several unclear assessments related to randomization; unclear to high risk for selective reporting.
2Wide confidence interval that includes no effect and appreciable benefit and/or harm.
3Total population size < 400.
4Majority of all individual studies had < 100 total participants.
5Considerable unexplained heterogeneity exists between studies.
6Different NSAIDs studied.

Figuras y tablas -
Summary of findings 3. Mean pain intensity over a 4‐hour period
Summary of findings 4. Mean pain intensity over a 6‐hour period

IV paracetamol compared to placebo or other analgesics for postoperative pain

Patient or population: patients with postoperative pain
Settings: hospital
Intervention: IV paracetamol
Comparison: placebo or other analgesics

Outcomes

Illustrative comparative risks* (95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Paracetamol vs placebo

The mean pain intensity over a 6‐hour period was:
7.48 lower (8.98 to 5.97 lower)

837
(12 studies)

⊕⊕⊝⊝
low1,2

Paracetamol vs NSAIDs

The mean pain intensity over a 6‐hour period was:
2.95 higher (1.18 to 4.72 higher)

524
(9 studies)

⊕⊝⊝⊝
very low2,3,4

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; NSAIDs: nonsteroidal anti‐inflammatory drugs

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Majority of all individual studies had < 100 total participants.
2Considerable unexplained heterogeneity exists between studies.
3See 'Risk of bias' tables: several unclear assessments related to randomization; unclear to high risk for selective reporting.
4Different NSAIDs studied.

Figuras y tablas -
Summary of findings 4. Mean pain intensity over a 6‐hour period
Summary of findings 5. Proportion of participants receiving additional analgesic medication

IV paracetamol/propacetamol compared to placebo or other analgesics for postoperative pain

Patient or population: patients with postoperative pain
Settings: hospital
Intervention: IV paracetamol/propacetamol
Comparison: placebo or other analgesics

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Assumed risk

Corresponding risk

Placebo or other analgesics

IV paracetamol/propacetamol

Para/propacetamol vs placebo

820 per 1000

574 per 1000
(525 to 631)

RR 0.7
(0.64 to 0.77)

859
(9 studies)

⊕⊕⊝⊝
low1,2

Paracetamol vs placebo

892 per 1000

669 per 1000
(616 to 732)

RR 0.75
(0.69 to 0.82)

655
(6 studies)

⊕⊕⊝⊝
low1,2

Propacetamol vs placebo

625 per 1000

306 per 1000
(219 to 431)

RR 0.49
(0.35 to 0.69)

204
(3 studies)

⊕⊕⊝⊝
low1,2,3,4,5

Para/propacetamol vs NSAIDs

284 per 1000

338 per 1000
(247 to 463)

RR 1.19
(0.87 to 1.63)

309
(5 studies)

⊕⊝⊝⊝
very low1,3,4,6,7

Paracetamol vs NSAIDs

200 per 1000

216 per 1000
(118 to 396)

RR 1.08
(0.59 to 1.98)

120
(2 studies)

⊕⊝⊝⊝
very low1,3,4,6,7

Propacetamol vs NSAIDs

337 per 1000

414 per 1000
(290 to 596)

RR 1.23
(0.86 to 1.77)

189
(3 studies)

⊕⊝⊝⊝
very low1,3,4,6,7

Propacetamol vs opioids

86 per 1000

157 per 1000
(62 to 398)

RR 1.83
(0.72 to 4.64)

139
(2 studies)

⊕⊝⊝⊝
very low1,3,4,7

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; NSAIDs: nonsteroidal anti‐inflammatory drugs; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1See 'Risk of bias' tables: several unclear assessments related to randomization and attrition bias; unclear to high risk for selective outcome reporting.
2Considerable unexplained heterogeneity exists between studies.
3Majority of all individual studies had < 100 total participants.
4Total # events < 300.
5Large effect.
6Different NSAIDs studied.
7Wide confidence interval that includes no effect and appreciable benefit and/or harm.

Figuras y tablas -
Summary of findings 5. Proportion of participants receiving additional analgesic medication
Summary of findings 6. Opioid consumption (IV morphine equivalents) over 6 hours

IV paracetamol/propacetamol compared to placebo or other analgesics for postoperative pain

Patient or population: patients with postoperative pain
Settings: hospital
Intervention: IV paracetamol/propacetamol
Comparison: placebo or other analgesics

Outcomes

Illustrative comparative risks* (95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Para/propacetamol vs placebo
see footnote1

The mean opioid consumption (IV morphine equivalents) over 6 hours was:
1.92 lower (2.41 to 1.42 lower)

777
(13 studies)

⊕⊕⊕⊝
moderate2,3

Paracetamol vs placebo
see footnote1

The mean opioid consumption (IV morphine equivalents) over 6 hours was:
1.83 lower (2.35 to 1.31 lower)

404
(8 studies)

⊕⊕⊝⊝
low2,3,4

Propacetamol vs placebo
see footnote1

The mean opioid consumption (IV morphine equivalents) over 6 hours was:
2.67 lower (4.21 to 1.13 lower)

373
(6 studies)

⊕⊕⊝⊝
low2,4,5

Para/propacetamol vs NSAIDs
see footnote1

The mean opioid consumption (IV morphine equivalents) over 6 hours was:
0.12 lower (0.37 lower to 0.12 higher)

540
(8 studies)

⊕⊝⊝⊝
very low2,3,6

Paracetamol vs NSAIDs
see footnote1

The mean opioid consumption (IV morphine equivalents) over 6 hours was:
0.81 higher (0.87 lower to 2.49 higher)

160
(3 studies)

⊕⊝⊝⊝
very low3,5,6,7

Propacetamol vs NSAIDs
see footnote1

The mean opioid consumption (IV morphine equivalents) over 6 hours was:
0.14 lower (0.39 lower to 0.11 higher)

380
(5 studies)

⊕⊝⊝⊝
very low5,6,7

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; NSAIDs: nonsteroidal anti‐inflammatory drugs

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Mean opioid consumption (in mg) over 6 hours in each treatment arm converted into IV morphine‐equivalents, using commonly used and widely accepted opioid conversion tables.
2See 'Risk of bias' tables: several unclear assessments related to randomization, unclear risk for selective reporting.
3Majority of all individual studies had < 100 participants.
4Considerable unexplained heterogeneity exists between studies.
5Total population size < 400.
6Different NSAIDs studied.
7Wide confidence interval that includes no effect and appreciable benefit and/or harm.

Figuras y tablas -
Summary of findings 6. Opioid consumption (IV morphine equivalents) over 6 hours
Summary of findings 7. Proportion of participants vomiting

IV paracetamol/propacetamol compared to placebo or other analgesics for postoperative pain

Patient or population: patients with postoperative pain
Settings: hospital
Intervention: IV paracetamol/propacetamol
Comparison: placebo or other analgesics

Outcomes

Illustrative comparative risks* (95% CI)

Relative effect
(95% CI)

No of participants
(studies)

Quality of the evidence
(GRADE)

Assumed risk

Corresponding risk

Placebo or other analgesics

IV paracetamol/propacetamol

Para/propacetamol vs placebo

208 per 1000

145 per 1000
(118 to 181)

RR 0.7
(0.57 to 0.87)

1414
(15 studies)

⊕⊝⊝⊝
very low1,2,3,4

Paracetamol vs placebo

263 per 1000

168 per 1000
(134 to 210)

RR 0.64
(0.51 to 0.8)

1037
(13 studies)

⊕⊝⊝⊝
very low1,3,4

Propacetamol vs placebo

45 per 1000

74 per 1000
(34 to 158)

RR 1.62
(0.75 to 3.48)

377
(3 studies)

⊕⊕⊝⊝
low3,5

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; NNH = number needed to treat to harm; RR: risk ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

1Majority of all individual studies had < 100 participants.
2Considerable unexplained heterogeneity exists between studies.
3Total # events < 300.
4Publication bias suspected in favor of a lower occurrence of vomiting in the paracetamol and/or propacetamol arm; NNH > 10.
5Wide confidence interval that includes no effect and appreciable benefit and/or harm.

Figuras y tablas -
Summary of findings 7. Proportion of participants vomiting
Table 1. Publication bias risk assessment: efficacy outcomes

Comparison/outcome

Number of studies

Number of participants

n with outcome/total

% with outcome

Risk difference

NNT

Susceptibility to publication bias

Active

Control

Active

Control

Comparison 1. Number of participants with > 50% pain relief over 4 hours

1 Paracetamol or propacetamol vs placebo

11

1149

250/687

72/462

36

16

0.23 (0.18 to 0.27)

5

1492

1.1 Paracetamol vs placebo

5

393

84/272

8/121

31

7

0.24 (0.17 to 0.31)

5

549

1.2 Propacetamol vs placebo

8

756

166/415

64/341

40

19

0.22 (0.17 to 0.27)

5

906

Comparison 2. Number of participants with > 50% pain relief over 6 hours

1 Paracetamol or propacetamol vs placebo

10

1143

200/708

42/435

28

10

0.18 (0.14 to 0.22)

6

913

1.1 Paracetamol vs placebo

6

532

109/364

14/168

30

8

0.22 (0.16 to 0.29)

5

637

1.2 Propacetamol vs placebo

6

611

91/344

28/267

26

10

0.15 (0.10 0.20)

7

305

2. Paracetamol or propacetamol vs NSAIDs

5

355

95/192

103/163

50

63

‐0.13 (‐0.23 to ‐0.03)

8*

107

Comparison 5. Number of participants requiring rescue medication

1 Paracetamol or propacetamol vs placebo

9

859

295/476

314/383

62

82

‐0.25 (‐0.30 to ‐0.19)

4

1289

1.1 Paracetamol vs placebo

6

655

267/376

249/279

71

89

‐0.22 (‐0.28 to ‐0.17)

5

785

1.2 Propacetamol vs placebo

3

204

31/100

65/104

31

62

‐0.32 (‐0.44 to ‐0.19)

4

449

Comparison 9. Global evaluation rated as good/satisfied or excellent/very satisfied

1 Paracetamol or propacetamol vs placebo

16

2015

787/1100

529/915

72

58

0.19 (0.15 to 0.23)

6

1816

1.1 Paracetamol vs placebo

9

876

355/508

207/368

70

56

0.24 (0.19 to 0.29)

5

1225

1.2 Propacetamol vs placebo

9

1139

432/592

322/547

73

59

0.15 (0.10 to 0.21)

7

569

2. Paracetamol or propacetamol vs NSAIDs

11

795

306/410

313/385

75

81

‐0.06 (‐0.11 to ‐4.81)

17*

NNT > 10

*NSAID superior

Figuras y tablas -
Table 1. Publication bias risk assessment: efficacy outcomes
Table 2. Publication bias risk assessment: safety outcomes

Comparison/outcome

Number of studies

Number of participants

n with outcome/total

% with outcome

Risk difference

NNH

Susceptibility to publication bias

Active

Control

Active

Control

Comparison 11. Number of participants with adverse events

1 Paracetamol or propacetamol vs placebo

20

2359

557/1278

400/1081

44

37

0.04 (0.01 to 0.08)

25

NNH > 10

1.2 Propacetamol vs placebo

10

1409

278/740

197/669

38

29

0.05 (0.01 to 0.10)

20

NNH > 10

Comparison 14. Number of participants withdrawing due to lack of efficacy

1.2 Propacetamol vs placebo

14

889

25/477

47/412

5

11

‐0.05 (‐0.08 to ‐0.02)

20*

NNH > 10

Comparison 15. Number of participants with pain on infusion

2. Propacetamol vs placebo

6

645

75/333

4/312

23

1

0.20 (0.16 to 0.24)

5

645

3. Propacetamol vs paracetamol

3

362

71/182

8/180

39

4

0.35 (0.27 to 0.42)

3

904

Comparison 16. Individual adverse events: paracetamol or propacetamol vs placebo

1. Nausea: Paracetamol or propacetamol vs placebo

15

1267

189/660

213/607

29

35

‐0.05 (‐0.10 to ‐0.01)

20*

NNH > 10

1.1. Nausea: Paracetamol vs placebo

13

1037

153/520

196/517

29

38

‐0.09 (‐0.14 to ‐0.04)

11*

NNH > 10

2. Vomiting: Paracetamol or propacetamol vs placebo

15

1414

103/721

144/693

14

21

‐0.06 (‐0.10 to ‐0.03)

17*

NNH > 10

2.1. Vomiting: Paracetamol vs placebo

13

1037

88/520

136/517

17

26

‐0.10 (‐0.14 to ‐0.05)

10*

NNH > 10

Comparison 18. Individual adverse events: paracetamol or propacetamol vs opioids

1. Nausea: Paracetamol or propacetamol vs opioids

6

545

19/272

48/273

7

18

‐0.11 (‐0.16 to ‐0.05)

10*

55

1.1 Nausea: Paracetamol vs opioids

4

438

12/219

39/219

5

18

‐0.12 (‐0.18 to ‐0.07)

9*

88

2. Vomiting: Paracetamol or propacetamol vs opioids

5

495

6/247

20/248

2

8

‐0.06 (‐0.09 to ‐0.02)

17*

NNH > 10

2.1. Vomiting: Paracetamol vs opioids

3

388

4/194

16/194

2

8

‐0.06 (‐0.10 to ‐0.02)

17*

NNH > 10

6.1. Sedation: Paracetamol vs opioids

3

354

2/176

26/178

1

15

‐0.14 (‐0.18 to ‐0.09)

8*

142

*lower occurrence of adverse event in paracetamol and/or propacetamol arm

Figuras y tablas -
Table 2. Publication bias risk assessment: safety outcomes
Comparison 1. Number of participants with > 50% pain relief over 4 hours

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

11

1149

Risk Ratio (M‐H, Fixed, 95% CI)

2.53 [2.01, 3.19]

1.1 Paracetamol vs placebo

5

393

Risk Ratio (M‐H, Fixed, 95% CI)

4.80 [2.30, 10.00]

1.2 Propacetamol vs placebo

8

756

Risk Ratio (M‐H, Fixed, 95% CI)

2.19 [1.74, 2.77]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

5

353

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.86, 1.18]

2.1 Paracetamol vs NSAIDs

2

130

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.72, 1.13]

2.2 Propacetamol vs NSAIDs

3

223

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.86, 1.34]

3 Propacetamol vs opioids Show forest plot

1

61

Risk Ratio (M‐H, Fixed, 95% CI)

1.16 [0.85, 1.59]

4 Paracetamol vs propacetamol Show forest plot

3

361

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.77, 1.24]

Figuras y tablas -
Comparison 1. Number of participants with > 50% pain relief over 4 hours
Comparison 2. Number of participants with > 50% pain relief over 6 hours

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

10

1143

Risk Ratio (M‐H, Fixed, 95% CI)

2.86 [2.10, 3.91]

1.1 Paracetamol vs placebo

6

532

Risk Ratio (M‐H, Fixed, 95% CI)

3.65 [2.15, 6.21]

1.2 Propacetamol vs placebo

6

611

Risk Ratio (M‐H, Fixed, 95% CI)

2.40 [1.64, 3.50]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

5

355

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.66, 0.95]

2.1 Paracetamol vs NSAIDs

3

212

Risk Ratio (M‐H, Fixed, 95% CI)

0.82 [0.66, 1.02]

2.2 Propacetamol vs NSAIDs

2

143

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.56, 1.02]

3 Propacetamol vs opioids Show forest plot

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.95 [0.83, 1.09]

4 Paracetamol vs propacetamol Show forest plot

3

361

Risk Ratio (M‐H, Fixed, 95% CI)

0.94 [0.73, 1.20]

Figuras y tablas -
Comparison 2. Number of participants with > 50% pain relief over 6 hours
Comparison 3. Pain intensity at 4 h

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol vs placebo Show forest plot

6

485

Mean Difference (IV, Fixed, 95% CI)

‐1.21 [‐3.73, 1.31]

2 Paracetamol vs NSAIDs Show forest plot

6

350

Mean Difference (IV, Fixed, 95% CI)

5.02 [3.18, 6.86]

3 Paracetamol vs opioids

0

0

Mean Difference (IV, Fixed, 95% CI)

0.0 [0.0, 0.0]

4 Paracetamol vs ketamine Show forest plot

1

80

Mean Difference (IV, Fixed, 95% CI)

‐12.0 [‐19.23, ‐4.77]

Figuras y tablas -
Comparison 3. Pain intensity at 4 h
Comparison 4. Pain intensity at 6 h

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol vs placebo Show forest plot

12

837

Mean Difference (IV, Fixed, 95% CI)

‐7.48 [‐8.98, ‐5.97]

2 Paracetamol vs NSAIDs Show forest plot

9

524

Mean Difference (IV, Fixed, 95% CI)

2.95 [1.18, 4.72]

3 Paracetamol vs opioids Show forest plot

1

50

Mean Difference (IV, Fixed, 95% CI)

3.0 [‐1.57, 7.57]

4 Paracetamol vs ketamine Show forest plot

1

80

Mean Difference (IV, Fixed, 95% CI)

‐13.0 [‐18.28, ‐7.72]

Figuras y tablas -
Comparison 4. Pain intensity at 6 h
Comparison 5. Number of participants requiring rescue medication

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

9

859

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.64, 0.77]

1.1 Paracetamol vs placebo

6

655

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.69, 0.82]

1.2 Propacetamol vs placebo

3

204

Risk Ratio (M‐H, Fixed, 95% CI)

0.49 [0.35, 0.69]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

5

309

Risk Ratio (M‐H, Fixed, 95% CI)

1.19 [0.87, 1.63]

2.1 Paracetamol vs NSAIDs

2

120

Risk Ratio (M‐H, Fixed, 95% CI)

1.08 [0.59, 1.98]

2.2 Propacetamol vs NSAIDs

3

189

Risk Ratio (M‐H, Fixed, 95% CI)

1.23 [0.86, 1.77]

3 Propacetamol vs opioids Show forest plot

2

139

Risk Ratio (M‐H, Fixed, 95% CI)

1.83 [0.72, 4.64]

4 Paracetamol vs propacetamol Show forest plot

1

161

Risk Ratio (M‐H, Fixed, 95% CI)

1.33 [0.82, 2.17]

Figuras y tablas -
Comparison 5. Number of participants requiring rescue medication
Comparison 6. Time to rescue medication (minutes)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

9

839

Mean Difference (IV, Fixed, 95% CI)

6.43 [4.54, 8.32]

1.1 Paracetamol vs placebo

6

523

Mean Difference (IV, Fixed, 95% CI)

5.78 [3.86, 7.71]

1.2 Propacetamol vs placebo

3

316

Mean Difference (IV, Fixed, 95% CI)

23.72 [13.79, 33.65]

2 Paracetamol vs NSAIDs Show forest plot

2

138

Mean Difference (IV, Fixed, 95% CI)

‐1.14 [‐36.21, 33.92]

Figuras y tablas -
Comparison 6. Time to rescue medication (minutes)
Comparison 7. Opioid consumption (IV morphine equivalents) over 4 hours

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

6

255

Mean Difference (IV, Fixed, 95% CI)

‐1.42 [‐1.81, ‐1.03]

1.1 Paracetamol vs placebo

4

141

Mean Difference (IV, Fixed, 95% CI)

‐1.33 [‐1.75, ‐0.91]

1.2 Propacetamol vs placebo

2

114

Mean Difference (IV, Fixed, 95% CI)

‐2.05 [‐3.15, ‐0.95]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

3

294

Mean Difference (IV, Fixed, 95% CI)

‐0.19 [‐0.37, ‐0.02]

2.1 Paracetamol vs NSAIDs

2

118

Mean Difference (IV, Fixed, 95% CI)

0.28 [‐1.04, 1.59]

2.2 Propacetamol vs NSAIDs

1

176

Mean Difference (IV, Fixed, 95% CI)

‐0.20 [‐0.38, ‐0.02]

3 Propacetamol vs opioids Show forest plot

1

80

Mean Difference (IV, Fixed, 95% CI)

‐1.0 [‐3.09, 1.09]

Figuras y tablas -
Comparison 7. Opioid consumption (IV morphine equivalents) over 4 hours
Comparison 8. Opioid consumption (IV morphine equivalents) over 6 hours

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

13

777

Mean Difference (IV, Fixed, 95% CI)

‐1.92 [‐2.41, ‐1.42]

1.1 Paracetamol vs placebo

8

404

Mean Difference (IV, Fixed, 95% CI)

‐1.83 [‐2.35, ‐1.31]

1.2 Propacetamol vs placebo

6

373

Mean Difference (IV, Fixed, 95% CI)

‐2.67 [‐4.21, ‐1.13]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

8

540

Mean Difference (IV, Fixed, 95% CI)

‐0.12 [‐0.37, 0.12]

2.1 Paracetamol vs NSAIDs

3

160

Mean Difference (IV, Fixed, 95% CI)

0.81 [‐0.87, 2.49]

2.2 Propacetamol vs NSAIDs

5

380

Mean Difference (IV, Fixed, 95% CI)

‐0.14 [‐0.39, 0.11]

3 Propacetamol vs opioids Show forest plot

1

80

Mean Difference (IV, Fixed, 95% CI)

‐0.5 [‐3.01, 2.01]

4 Paracetamol vs propacetamol Show forest plot

1

98

Mean Difference (IV, Fixed, 95% CI)

‐0.40 [‐4.15, 3.35]

Figuras y tablas -
Comparison 8. Opioid consumption (IV morphine equivalents) over 6 hours
Comparison 9. Global evaluation rated as good/satisfied or excellent/very satisfied

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

16

2015

Risk Ratio (M‐H, Fixed, 95% CI)

1.34 [1.25, 1.43]

1.1 Paracetamol vs placebo

9

876

Risk Ratio (M‐H, Fixed, 95% CI)

1.45 [1.31, 1.60]

1.2 Propacetamol vs placebo

9

1139

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [1.16, 1.37]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

11

795

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.87, 1.00]

2.1 Paracetamol vs NSAIDs

6

247

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.91, 1.04]

2.2 Propacetamol vs NSAIDs

5

548

Risk Ratio (M‐H, Fixed, 95% CI)

0.91 [0.82, 1.01]

3 Propacetamol vs opioids Show forest plot

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.81, 1.23]

3.1 Propacetamol

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.81, 1.23]

4 Paracetamol vs propacetamol Show forest plot

2

263

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.83, 1.15]

Figuras y tablas -
Comparison 9. Global evaluation rated as good/satisfied or excellent/very satisfied
Comparison 10. Global evaluation using a numerical rating scale (0 to 10)

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

3

342

Mean Difference (IV, Fixed, 95% CI)

0.35 [0.04, 0.66]

1.1 Paracetamol vs placebo

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.10 [‐0.46, 0.26]

1.2 Propacetamol vs placebo

2

282

Mean Difference (IV, Fixed, 95% CI)

1.64 [1.04, 2.25]

2 Paracetamol vs NSAIDs Show forest plot

1

60

Mean Difference (IV, Fixed, 95% CI)

‐0.30 [‐0.63, 0.03]

3 Propacetamol vs opioids Show forest plot

2

141

Mean Difference (IV, Fixed, 95% CI)

0.40 [‐0.18, 0.98]

Figuras y tablas -
Comparison 10. Global evaluation using a numerical rating scale (0 to 10)
Comparison 11. Number of participants with adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

20

2359

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [1.01, 1.22]

1.1 Paracetamol vs placebo

12

950

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.93, 1.19]

1.2 Propacetamol vs placebo

10

1409

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [1.02, 1.35]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

6

471

Risk Ratio (M‐H, Fixed, 95% CI)

0.97 [0.72, 1.32]

2.1 Paracetamol vs NSAIDs

3

248

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.66, 1.68]

2.2 Propacetamol vs NSAIDs

3

223

Risk Ratio (M‐H, Fixed, 95% CI)

0.93 [0.62, 1.37]

3 Propacetamol vs opioids Show forest plot

1

61

Risk Ratio (M‐H, Fixed, 95% CI)

0.60 [0.29, 1.23]

Figuras y tablas -
Comparison 11. Number of participants with adverse events
Comparison 12. Number of participants with serious adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

10

970

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.19, 6.59]

1.1 Paracetamol vs placebo

6

634

Risk Ratio (M‐H, Fixed, 95% CI)

1.12 [0.19, 6.59]

1.2 Propacetamol vs placebo

5

336

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

9

798

Risk Ratio (M‐H, Fixed, 95% CI)

0.43 [0.11, 1.65]

2.1 Paracetamol vs NSAIDs

4

270

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.07, 15.26]

2.2 Propacetamol vs NSAIDs

5

528

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.07, 1.65]

3 Paracetamol or propacetamol vs opioids Show forest plot

3

191

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 71.51]

3.1 Paracetamol vs opioids

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Propacetamol vs opioids

2

141

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 71.51]

Figuras y tablas -
Comparison 12. Number of participants with serious adverse events
Comparison 13. Number of participants withdrawing due to adverse events

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

37

2654

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [0.56, 2.84]

1.1 Paracetamol vs placebo

27

1912

Risk Ratio (M‐H, Fixed, 95% CI)

1.25 [0.49, 3.17]

1.2 Propacetamol vs placebo

12

742

Risk Ratio (M‐H, Fixed, 95% CI)

1.29 [0.25, 6.68]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

24

1429

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.42, 3.12]

2.1 Paracetamol vs NSAIDs

19

1029

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.31, 3.22]

2.2 Propacetamol vs NSAIDs

5

400

Risk Ratio (M‐H, Fixed, 95% CI)

1.67 [0.22, 12.37]

3 Paracetamol or propacetamol vs opioids Show forest plot

6

505

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.95]

3.1 Paracetamol vs opioids

2

254

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Propacetamol vs opioids

4

251

Risk Ratio (M‐H, Fixed, 95% CI)

0.33 [0.01, 7.95]

4 Paracetamol vs ketamine Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figuras y tablas -
Comparison 13. Number of participants withdrawing due to adverse events
Comparison 14. Number of participants withdrawing due to lack of efficacy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol or propacetamol vs placebo Show forest plot

38

2600

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.38, 0.79]

1.1 Paracetamol vs placebo

26

1711

Risk Ratio (M‐H, Fixed, 95% CI)

0.52 [0.10, 2.78]

1.2 Propacetamol vs placebo

14

889

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.38, 0.80]

2 Paracetamol or propacetamol vs NSAIDs Show forest plot

24

1393

Risk Ratio (M‐H, Fixed, 95% CI)

1.30 [0.81, 2.08]

2.1 Paracetamol vs NSAIDs

18

934

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 71.89]

2.2 Propacetamol vs NSAIDs

6

459

Risk Ratio (M‐H, Fixed, 95% CI)

1.26 [0.78, 2.03]

3 Paracetamol or propacetamol vs opioids Show forest plot

6

505

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.25, 100.97]

3.1 Paracetamol vs opioids

2

254

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

3.2 Propacetamol vs opioids

4

251

Risk Ratio (M‐H, Fixed, 95% CI)

5.0 [0.25, 100.97]

4 Paracetamol vs ketamine Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

Figuras y tablas -
Comparison 14. Number of participants withdrawing due to lack of efficacy
Comparison 15. Number of participants with pain on infusion

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Paracetamol vs placebo Show forest plot

3

467

Risk Ratio (M‐H, Fixed, 95% CI)

3.05 [0.80, 11.54]

2 Propacetamol vs placebo Show forest plot

6

645

Risk Ratio (M‐H, Fixed, 95% CI)

13.07 [5.35, 31.98]

3 Propacetamol vs paracetamol Show forest plot

3

362

Risk Ratio (M‐H, Fixed, 95% CI)

8.31 [4.20, 16.46]

Figuras y tablas -
Comparison 15. Number of participants with pain on infusion
Comparison 16. Individual adverse events: paracetamol or propacetamol vs placebo

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Nausea Show forest plot

15

1267

Risk Ratio (M‐H, Fixed, 95% CI)

0.84 [0.73, 0.98]

1.1 Paracetamol vs placebo

13

1037

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.66, 0.90]

1.2 Propacetamol vs placebo

3

230

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [0.98, 2.69]

2 Vomiting Show forest plot

15

1414

Risk Ratio (M‐H, Fixed, 95% CI)

0.70 [0.57, 0.87]

2.1 Paracetamol vs placebo

13

1037

Risk Ratio (M‐H, Fixed, 95% CI)

0.64 [0.51, 0.80]

2.2 Propacetamol vs placebo

3

377

Risk Ratio (M‐H, Fixed, 95% CI)

1.62 [0.75, 3.48]

3 Nausea/vomiting Show forest plot

10

1064

Risk Ratio (M‐H, Fixed, 95% CI)

0.90 [0.74, 1.08]

3.1 Paracetamol vs placebo

4

191

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.57, 1.70]

3.2 Propacetamol vs placebo

6

873

Risk Ratio (M‐H, Fixed, 95% CI)

0.88 [0.72, 1.08]

4 Pruritus Show forest plot

7

618

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.60, 1.40]

4.1 Paracetamol vs placebo

5

320

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.64, 1.72]

4.2 Propacetamol vs placebo

3

298

Risk Ratio (M‐H, Fixed, 95% CI)

0.67 [0.29, 1.51]

5 Respiratory depression Show forest plot

11

1082

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.31, 1.92]

5.1 Paracetamol vs placebo

6

363

Risk Ratio (M‐H, Fixed, 95% CI)

0.28 [0.03, 2.65]

5.2 Propacetamol vs placebo

5

719

Risk Ratio (M‐H, Fixed, 95% CI)

0.99 [0.35, 2.80]

6 Sedation Show forest plot

10

566

Risk Ratio (M‐H, Fixed, 95% CI)

1.00 [0.66, 1.51]

6.1 Paracetamol vs placebo

6

341

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.42, 2.01]

6.2 Propacetamol vs placebo

4

225

Risk Ratio (M‐H, Fixed, 95% CI)

1.05 [0.65, 1.69]

7 Urinary retention Show forest plot

8

1050

Risk Ratio (M‐H, Fixed, 95% CI)

1.06 [0.68, 1.66]

7.1 Paracetamol vs placebo

5

373

Risk Ratio (M‐H, Fixed, 95% CI)

1.36 [0.28, 6.66]

7.2 Propacetamol vs placebo

3

677

Risk Ratio (M‐H, Fixed, 95% CI)

1.04 [0.65, 1.66]

8 Allergy/skin rash/local reaction Show forest plot

7

1131

Risk Ratio (M‐H, Fixed, 95% CI)

1.54 [0.61, 3.91]

8.1 Paracetamol vs placebo

4

370

Risk Ratio (M‐H, Fixed, 95% CI)

1.01 [0.24, 4.34]

8.2 Propacetamol vs placebo

4

761

Risk Ratio (M‐H, Fixed, 95% CI)

1.97 [0.57, 6.73]

Figuras y tablas -
Comparison 16. Individual adverse events: paracetamol or propacetamol vs placebo
Comparison 17. Individual adverse events: paracetamol or propacetamol vs NSAIDs

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Nausea Show forest plot

11

856

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.90, 1.28]

1.1 Paracetamol vs NSAIDs

8

424

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.74, 1.31]

1.2 Propacetamol vs NSAIDs

3

432

Risk Ratio (M‐H, Fixed, 95% CI)

1.15 [0.92, 1.44]

2 Vomiting Show forest plot

11

856

Risk Ratio (M‐H, Fixed, 95% CI)

1.17 [0.89, 1.55]

2.1 Paracetamol vs NSAIDs

8

424

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.77, 1.68]

2.2 Propacetamol vs NSAIDs

3

432

Risk Ratio (M‐H, Fixed, 95% CI)

1.21 [0.81, 1.81]

3 Nausea/vomiting Show forest plot

8

408

Risk Ratio (M‐H, Fixed, 95% CI)

1.11 [0.62, 1.97]

3.1 Paracetamol vs NSAIDs

4

208

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.42, 2.39]

3.2 Propacetamol vs NSAIDs

4

200

Risk Ratio (M‐H, Fixed, 95% CI)

1.2 [0.55, 2.60]

4 Pruritus Show forest plot

8

558

Risk Ratio (M‐H, Fixed, 95% CI)

0.96 [0.69, 1.34]

4.1 Paracetamol vs NSAIDs

5

286

Risk Ratio (M‐H, Fixed, 95% CI)

1.07 [0.75, 1.51]

4.2 Propacetamol vs NSAIDs

3

272

Risk Ratio (M‐H, Fixed, 95% CI)

0.77 [0.37, 1.60]

5 Respiratory depression Show forest plot

9

510

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.17, 3.26]

5.1 Paracetamol vs NSAIDs

8

470

Risk Ratio (M‐H, Fixed, 95% CI)

0.75 [0.17, 3.26]

5.2 Propacetamol vs NSAIDs

1

40

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Sedation Show forest plot

6

278

Risk Ratio (M‐H, Fixed, 95% CI)

2.6 [0.63, 10.75]

6.1 Paracetamol vs NSAIDs

4

208

Risk Ratio (M‐H, Fixed, 95% CI)

1.0 [0.07, 14.90]

6.2 Propacetamol vs NSAIDs

2

70

Risk Ratio (M‐H, Fixed, 95% CI)

3.67 [0.63, 21.22]

7 Urinary retention Show forest plot

6

390

Risk Ratio (M‐H, Fixed, 95% CI)

1.09 [0.51, 2.32]

7.1 Paracetamol vs NSAIDs

4

178

Risk Ratio (M‐H, Fixed, 95% CI)

0.98 [0.24, 4.02]

7.2 Propacetamol vs NSAIDs

2

212

Risk Ratio (M‐H, Fixed, 95% CI)

1.14 [0.47, 2.78]

8 Allergy/skin rash/local reaction Show forest plot

8

399

Risk Ratio (M‐H, Fixed, 95% CI)

0.73 [0.24, 2.26]

8.1 Paracetamol vs NSAIDs

6

290

Risk Ratio (M‐H, Fixed, 95% CI)

1.03 [0.26, 4.02]

8.2 Propacetamol vs NSAIDs

2

109

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.04, 3.16]

Figuras y tablas -
Comparison 17. Individual adverse events: paracetamol or propacetamol vs NSAIDs
Comparison 18. Individual adverse events: paracetamol or propacetamol vs opioids

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Nausea Show forest plot

6

545

Risk Ratio (M‐H, Fixed, 95% CI)

0.40 [0.24, 0.65]

1.1 Paracetamol vs opioids

4

438

Risk Ratio (M‐H, Fixed, 95% CI)

0.31 [0.17, 0.56]

1.2 Propacetamol vs opioids

2

107

Risk Ratio (M‐H, Fixed, 95% CI)

0.79 [0.32, 1.91]

2 Vomiting Show forest plot

5

495

Risk Ratio (M‐H, Fixed, 95% CI)

0.30 [0.12, 0.72]

2.1 Paracetamol vs opioids

3

388

Risk Ratio (M‐H, Fixed, 95% CI)

0.25 [0.08, 0.71]

2.2 Propacetamol vs opioids

2

107

Risk Ratio (M‐H, Fixed, 95% CI)

0.51 [0.10, 2.62]

3 Nausea/vomiting Show forest plot

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.15, 1.64]

3.1 Propacetamol vs opioids

1

30

Risk Ratio (M‐H, Fixed, 95% CI)

0.5 [0.15, 1.64]

4 Pruritus Show forest plot

3

157

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.21, 1.43]

4.1 Paracetamol vs opioids

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

1.5 [0.27, 8.22]

4.2 Propacetamol vs opioids

2

107

Risk Ratio (M‐H, Fixed, 95% CI)

0.34 [0.10, 1.19]

5 Respiratory depression Show forest plot

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

5.1 Paracetamol vs opioids

1

50

Risk Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

6 Sedation Show forest plot

3

354

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.03, 0.34]

6.1 Paracetamol vs opioids

3

354

Risk Ratio (M‐H, Fixed, 95% CI)

0.10 [0.03, 0.34]

Figuras y tablas -
Comparison 18. Individual adverse events: paracetamol or propacetamol vs opioids
Comparison 19. Individual adverse events: paracetamol vs ketamine

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Nausea Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.92 [0.66, 1.30]

2 Vomiting Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

0.55 [0.22, 1.33]

3 Sedation Show forest plot

1

80

Risk Ratio (M‐H, Fixed, 95% CI)

3.0 [0.13, 71.51]

Figuras y tablas -
Comparison 19. Individual adverse events: paracetamol vs ketamine