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Ketamina intravenosa perioperatoria para el dolor posoperatorio agudo en adultos

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Referencias

Referencias de los estudios incluidos en esta revisión

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Abdolahi 2013 {published data only}

Abdolahi M, Soltani HA, Montazeri K, Soleymani B. Preemptive low-dose of ketamine does not effective on anesthetic consumption, perioperative analgesic requirement and postoperative pain, nausea and vomiting in painful ophthalmic surgery. Journal of Research in Medical Sciences 2013;18(7):583-7. CENTRAL

Adam 2005 {published data only}

Adam F, Chauvin M, Du Manoir B, Langlois M, Sessler DI, Fletcher D. Small dose ketamine improves postoperative analgesia and rehabilitation after total knee arthroplasty. Anesthesia and Analgesia 2005;100(2):475-80. CENTRAL [DOI: 10.1213/01.ANE.0000142117.82241.DC]

Adriaenssens 1999 {published data only}

Adriaenssens G, Vermeyen KM, Hoffmann VLH, Mertens E, Adriaensen HF. Postoperative analgesia with i.v. patient-controlled morphine: effect of adding ketamine. British Journal of Anaesthesia 1999;83(3):393-6. CENTRAL

Aida 2000 {published data only}

Aida S, Yamakura T, Baba H, Taga K, Fukuda S, Shimoji K. Preemptive analgesia by intravenous low-dose ketamine and epidural morphine in gastrectomy. Anesthesiology 2000;92:1624-30. CENTRAL

Aqil 2011 {published data only}

Aqil M, Haq AU, Rasheed A, Hussain A, Khan M, Abdulhamid A-S. Is preemptive analgesic effect of ketamine dose dependent? Effect of increasing dose on post septorhinoplasty pain. Pakistan Journal of Medical Sciences 2011;27(3):608-12. CENTRAL

Argiriadou 2004 {published data only}

Argiriadou H, Himmelseher S, Papagiannopoulou P, Georgiou M, Kanakoudis F, Giala M, et al. Improvement of pain treatment after major abdominal surgery by intravenous S(+) -ketamine. Anesthesia and Analgesia 2004;98:1413-8. CENTRAL [DOI: 10.1213/01.ANE.0000111204.31815.2D]

Argiriadou 2011 {published data only}

Argiriadou H, Papagiannopoulou P, Foroulis CN, Anastasiadis K, Thomaidou E, Papakonstantinou C, et al. Intraoperative infusion of S(+) -ketamine enhances post-thoracotomy pain control compared with perioperative parecoxib when used in conjunction with thoracic paravertebral ropivacaine infusion. Journal of Cardiothoracic and Vascular Anesthesia 2011;25(3):455-61. CENTRAL [DOI: 10.1053/j.jvca.2010.07.011]

Arikan 2016 {published data only}

Arikan M, Aslan B, Arikan O, Horasanli E, But A. Comparison of the effects of magnesium and ketamine on postoperative pain and morphine consumption. A double-blind randomized controlled study. Acta Cirurgica Brasileira 2016;31(1):67-73. CENTRAL [DOI: http://dx.doi.org/10.1590/S0102-865020160010000010]

Ataskhoyi 2013 {published data only}

Ataskhoyi S, Negargar S, Hatami-Marandi P. Effects of the addition of low-dose ketamine to propofol-fentanyl anaesthesia during diagnostic gynaecological laparoscopy. European Journal of Obstetrics and Gynecology and Reproductive Biology 2013;170:247-50. CENTRAL

Aubrun 2008 {published data only}

Aubrun F, Gaillat C, Rosenthal D, Dupuis M, Mottet P, Marchetti F, et al. Effect of a low dose ketamine regimen on pain, mood, cognitive function and memory after major gynaecological surgery: a randomized, double-blind, placebo-controlled trial. European Journal of Anaesthesiology 2008;25:97-105. CENTRAL [DOI: 10.1017/S0265021507002566]

Aveline 2006 {published data only}

Aveline C, Le Hetet H, Vautier P, Gautier JF, Bonnet F. Peroperative ketamine and morphine for postoperative pain control after lumbar disk surgery. European Journal of Pain 2006;10:653-8. CENTRAL [DOI: 10.1016/j.ejpain.2005.10.005]

Aveline 2009 {published data only}

Aveline C, Gautier JF, Vautier P, Cognet F, Le Hetet H, Attali JY, et al. Postoperative analgesia and early rehabilitation after total knee replacement: a comparison of continuous low-dose intravenous ketamine versus nefopam. European Journal of Pain 2009;13:613-9. CENTRAL [DOI: 10.1016/j.ejpain.2008.08.003]

Ayoglu 2005 {published data only}

Ayoglu H, Karadeniz Ü, Kunduracilar Z, Ayoglu FN, Erdemli Ö. The analgesic effect of magnesium sulphate and ketamine in patients undergoing laparoscopic cholecystectomy. The Pain Clinic 2005;17(1):45-53. CENTRAL

Barreveld 2013 {published data only}

Barreveld AM, Correll DJ, Liu X, Max B, McGowan JA, Shovel L, et al. Ketamine decreases postoperative pain scores in patients taking opioids for chronic pain: results of a prospective, randomized, double-blind study. Pain Medicine 2013;14:925-34. CENTRAL

Bilgen 2012 {published data only}

Bilgen S, Köner Ö, Türe H, Menda F, Ficicioglu C, Aykac B. Effect of three different doses of ketamine prior to general anesthesia on postoperative pain following Caesarean delivery: a prospective randomized study. Minerva Anestesiologica 2012;78(4):442-9. CENTRAL

Bornemann‐Cimenti 2016 {published data only}

Bornemann-Cimenti H, Wejbora M, Michaeli K, Edler A, Sandner-Kiesling A. The effects of minimal-dose versus low-dose S-ketamine on opioid consumption, hyperalgesia, and postoperative delirium: a triple-blinded, randomized, active- and placebo-controlled clinical trial. Minerva Anestesiologica 2016;82(10):1069-76. CENTRAL

Burstal 2001 {published data only}

Burstal R, Danjoux G, Hayes C, Lantry G. PCA ketamine and morphine after abdominal hysterectomy. Anaesthesia and Intensive Care 2001;29(3):246-51. CENTRAL

Cenzig 2014 {published data only}

Cenzig P, Gokcinar D, Topcu H, Cicek GS, Gogus N. Intraoperative low-dose ketamine infusion reduces acute postoperative pain following total knee replacement surgery: a prospective, randomized, placebo-controlled trial. Journal of the College of Physicians and Surgeons Pakistan 2014;24(5):299-303. CENTRAL

Chazan 2010 {published data only}

Chazan S, Buda I, Nesher N, Paz J, Weinbroum AA. Low-dose ketamine via intravenous patient-controlled analgesia device after various transthoracic procedures improves analgesia and patient and family satisfaction. Pain Management Nursing 2010;11(3):169-76. CENTRAL [DOI: 10.1016/j.pmn.2009.06.003]

Chen 2004 {published data only}

Chen JY, Bai L, You Yu YF, Zhou SJ. Effect of low dose ketamine during anesthesia on postoperative analgesia. Fudan University Journal of Medical Sciences 2004;31(1):81-3. CENTRAL

Choi 2015 {published data only}

Choi E, Lee H, Park HS, Lee HY, Kim YJ, Baik HJ. Effect of intraoperative infusion of ketamine on remifentanil-induced hyperalgesia. Korean Journal of Anesthesiology 2015;68(5):476-80. CENTRAL [DOI: 10.4097/kjae.2015.68.5.476]

Colombani 2008 {published data only}

Colombani S, Kabbani Y, Mathoulin-Pélissier S, Gékiere JP, Dixmérias F, Monnin D, et al. Administration of ketamine during induction and maintenance of anaesthesia in postoperative pain prevention. Clinical trial in oncology [Apport de l'administration de kétamine a l'induction et en entretien anesthésique dans la prévention de la douleur postopératoire. Essai clinique en oncologie]. Annales Francaises d'Anesthesie et de Reanimation 2008;27(3):202-7. CENTRAL

Crousier 2008 {published data only}

Crousier M, Cognat V, Khaled M, Guegniaud PY, Piriou V. Effect of ketamine on prevention of postmastectomy chronic pain. A pilot study [Effet de la kétamine dans la prévention des douleurs chronique post-mastectomies]. Annales Francaises d'Anesthesie et de Reanimation 2008;27:987-93. CENTRAL [DOI: 10.1016/j.annfar.2008.10.008]

D'Alonzo 2011 {published data only}

D'Alonzo RC, Bennett-Guerrero E, Podgoreanu M, D'Amico TA, Harpole DH, Shaw AD. A randomized, double blind, placebo controlled clinical trial of the preoperative use of ketamine for reducing inflammation and pain after thoracic surgery. Journal of Anesthesia 2011;25:672-8. CENTRAL [DOI: 10.1007/s00540-011-1206-4]

Dahi‐Taleghani 2014 {published data only}

Dahi-Taleghani M, Fazli B, Ghasemi M, Vosoughian M, Dabbagh A. Effect of intravenous patient controlled ketamine analgesia on postoperative pain in opium abusers. Anesthesiology and Pain Medicine 2014;4(1):e14129. CENTRAL

Dahl 2000 {published data only}

Dahl V, Ernoe PE, Steen T, Raeder JC, White PF. Does ketamine have preemptive effects in women undergoing abdominal hysterectomy procedures? Anesthesia and Analgesia 2000;90:1419-22. CENTRAL

Dal 2005 {published data only}

Dal D, Kose A, Honca M, Akinci SB, Basgul E, Aypar U. Efficacy of prophylactic ketamine in preventing postoperative shivering. British Journal of Anaesthesia 2005;95(2):189-92. CENTRAL [DOI: 10.1093/bja/aei148]

Dar 2012 {published data only}

Dar AM, Qasi SM, Sidiq S. A placebo-controlled comparison of ketamine with pethidine for the prevention of postoperative shivering. Southern African Journal of Anaesthesia and Analgesia 2012;18(6):340-3. CENTRAL [DOI: 10.1080/22201173.2012.10872875]

De Kock 2001 {published data only}

De Kock M, Lavand'homme P, Waterloos H. 'Balanced analgesia' in the perioperative period: is there a place for ketamine? Pain 2001;92:373-80. CENTRAL

Deng 2009 {published data only}

Deng G, Zheng J, Wang S, Tian B, Zhang S. Remifentanil combined with low-dose ketamine for postoperative analgesia of lower limb fracture: a double-blind, controlled study. Chinese Journal of Traumatology 2009;12(4):223-7. CENTRAL [DOI: 10.3760/cma.j.issn.1008-1275.2009.04.007]

Du 2011 {published data only}

Du J, Huang YG, Yu XR, Zhao N. Effects of preoperative ketamine on the endocrine-metabolic and inflammatory response to laparoscopic surgery. Chinese Medical Journal 2011;124(22):721-5. CENTRAL

Dualé 2009 {published data only}

Dualé C, Sibaud F, Guastella V, Vallet L, Gimbert YA, Taheri H, et al. Perioperative ketamine does not prevent chronic pain after thoracotomy. European Journal of Pain 2009;13:497-505. CENTRAL [DOI: 10.1016/j.ejpain.2008.06.013]

Dullenkopf 2009 {published data only}

Dullenkopf A, Müller R, Dillmann F, Wiedemeier P, Hegi TR, Gautschi S. An intraoperative pre-incision single dose of intravenous ketamine does not have an effect on postoperative analgesic requirements under clinical conditions. Anaesthesia and Intensive Care 2009;37(5):753-7. CENTRAL

Fiorelli 2015 {published data only}

Fiorelli A, Mazzella A, Passavanti B, Sansone P, Chiodini P, Iannotti M et al. Is pre-emptive administration of ketamine a significant adjunction to intravenous morphine analgesia for controlling postoperative pain? A randomized, double-blind, placebo-controlled clinical trial. Interactive Cardiovascular and Thoracic Surgery 2015;21:284-91. CENTRAL [DOI: 10.1093/icvts/ivv154]

Galinski 2007 {published data only}

Galinski SF, Pereira JA, Maestre Y, Francés S, Escolano F, Puig MM. The combination of intravenous dexamethasone and ketamine does not improve postoperative analgesia when compared to each drug individually. Pain Clinic 2007;19(5):223-9. CENTRAL [DOI: 10.1016/j.ajem.2006.11.016]

Ganne 2005 {published data only}

Ganne O, Abisseror M, Menault P, Malhiere S, Chambost V, Charpiat B, et al. Low-dose ketamine failed to spare morphine after a remifentanil-based anaesthesia for ear, nose and throat surgery. European Journal of Anaesthesiology 2005;22:426-30. CENTRAL [DOI: 10.1017/S0265021505000724]

Garcia‐Navia 2016 {published data only}

García-Navia JT, López JT, Egea-Guerrero JJ, Arenas AV, Gutiérrez TV. Effect of a single dose of lidocaine and ketamine on intraoperative opioids requirements in patients undergoing elective gynecological laparotomies under general anesthesia. A randomized, placebo controlled pilot study. Farmacia Hospitalaria 2016;40(1):44-51. CENTRAL [DOI: 10.7399/fh.2016.40.1.9339]

Garg 2016 {published data only}

Garg N, Panda NB, Gandhi GA, Bhagat H, Batra YK, Grover VK, et al. Comparison of small dose ketamine and dexmedetomidine infusion for postoperative analgesia in spine surgery - a prospective randomized double-blind placebo controlled study. Journal of Neurosurgical Anesthesiology 2016;28(1):27-31. CENTRAL

Gilabert Morell 2002 {published data only}

Gilabert Morell A, Sánchez Pérez C. Effect of low-dose intravenous ketamine in postoperative analgesia for hysterecomy and adnexectomy [Efecto de dosis bajas intravenosas de ketamina en la analgesia postoperatoria de histerectomía y anexectomía]. Revista Espańola de Anestesiologíga y Reanimación 2002;49(5):247-53. CENTRAL

Grady 2012 {published data only}

Grady MV, Mascha E, Sessler DI, Kurz A. The effect of perioperative intravenous lidocaine and ketamine on recovery after abdominal hysterectomy. Anesthesia and Analgesia 2012;115(5):1078-84. CENTRAL [DOI: 10.1213/ANE0b013e3182662e01]

Guignard 2002 {published data only}

Guignard B, Coste C, Costes H, Sessler DI, Lebrault C, Morris W, et al. Supplementing desflurane-remifentanil anesthesia with small-dose ketamine reduces perioperative opioid analgesic requirements. Anesthesia and Analgesia 2002;95:103-8. CENTRAL [DOI: 10.1213/01.ANE.0000020699.65934.0F]

Guillou 2003 {published data only}

Guillou N, Tanguy M, Seguin P, Branger P, Campion J, Mallédant Y. The effects of small-dose ketamine on morphine consumption in surgical intensive care unit patients after major abdominal surgery. Anesthesia and Analgesia 2003;97:843-7. CENTRAL [DOI: 10.1213/01.ANE.0000075837.67275.36]

Hadi 2010 {published data only}

Hadi BA, Al Ramadani R, Daas R, Naylor I, Zelkó R. Remifentanil in combination with ketamine versus remifentanil in spinal fusion surgery - a double blind study. International Journal of Clinical Pharmacology and Therapeutics 2010;48(8):542-8. CENTRAL [DOI: 10.5414/CPP48542]

Hadi 2013 {published data only}

Hadi BA, Daas R, Zelkó R. A randomized, controlled trial of a clinical pharmacist intervention in microdiscectomy surgery - low dose intravenous ketamine as an adjunct to standard therapy. Saudi Pharmaceutical Journal 2013;21:169-75. CENTRAL [DOI: 10.1016/j.jsps.2012.08.002]

Haliloglu 2015 {published data only}

Haliloglu M, Ozdemir M, Uzture N, Cenksoy PO, Bakan N. Perioperative low-dose ketamine improves postoperative analgesia following cesarean delivery with general anesthesia. The Journal of Maternal-Fetal & Neonatal Medicine 2016;29(6):962-6. CENTRAL [DOI: 10.3109/14767058.2015.1027190]

Hasanein 2011 {published data only}

Hasanein R, El-Sayed W, Nabil N, Elsayed G. The effect of combined remifentanil and low dose ketamine infusion in patients undergoing laparoscopic gastric bypass. Egyptian Journal of Anaesthesia 2011;27:255-60. CENTRAL [DOI: 10.1016/j.egja.2011.07.009]

Hayes 2004 {published data only}

Hayes C, Armstrong-Brown A, Burstal R. Perioperative intravenous ketamine infusion for the prevention of persistent post-amputation pain: a randomized, controlled trial. Anaesthesia and Intensive Care 2004;32(3):330-8. CENTRAL

Helmy 2015 {published data only}

Helmy N, Badawy AA, Hussein M, Reda H. Comparison of the preemptive analgesia of low dose ketamine versus magnesium sulphate on parturient undergoing cesarean section under general anesthesia. Egyptian Journal of Anaesthesia 2015;31:53-8. CENTRAL [DOI: 10.1016/j.egja.2014.12.006]

Hercock 1999 {published data only}

Hercock T, Gillham MJ, Sleigh J, Jones SF. The addition of ketamine to patient controlled morphine analgesia does not improve quality of analgesia after total abdominal hysterectomy. Acute Pain 1999;2(2):68-72. CENTRAL

Hu 2014 {published data only}

Hu J, Zhang F, Tong J, Ouyang W. Chronic postthoracotomy pain and perioperative ketamine infusion. Journal of Pain and Palliative Care Pharmacotherapy 2014;28:117-21. CENTRAL [DOI: 10.3109/15360288.2014.908992]

Ilkjaer 1998 {published data only}

Ilkjaer S, Nikolajsen L, Hansen TM, Wernberg M, Brennum J, Dahl JB. Effect of i.v. ketamine in combination with epidural bupivacaine or epidural morphine on postoperative pain and wound tenderness after renal surgery. British Journal of Anaesthesia 1998;81:707-12. CENTRAL

Jaksch 2002 {published data only}

Jaksch W, Lang S, Reichhalter R, Raab G, Dann K, Fitzal S. Perioperative small-dose S(+) -ketamine has no incremental beneficial effects on postoperative pain when standard-practice opioid infusions are used. Anesthesia and Analgesia 2002;94:981-6. CENTRAL

Javery 1996 {published data only}

Javery KB, Ussery TW, Steger HG, Colclough GW. Comparison of morphine and morphine with ketamine for postoperative analgesia. Canadian Journal of Anaesthesiology 1996;43(3):212-5. CENTRAL

Jendoubi 2017 {published data only}

Jendoubi A, Naceur IB, Bouzouita A, Trifa M, Ghedira S, Chebil S et al. A comparison between intravenous lidocaine and ketamine on acute and chronic pain after open nephrectomy: a prospective, double-blind, randomized, placebo-controlled study. Saudi Journal of Anaesthesia 2017;11(2):177-84. CENTRAL [DOI: 10.4103/1658-354X203027]

Joly 2005 {published data only}

Joly V, Richebe P, Guignard B, Fletcher D, Maurette P, Sessler DI et al. Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology 2005;103:147-55. CENTRAL

Joseph 2012 {published data only}

Joseph C, Gaillat F, Duponq R, Lieven R, Baumstarck K, Thomas P, et al. Is there any benefit to adding intravenous ketamine to patient-controlled epidural analgesia after thoracic surgery? A randomised double-blind study. European Journal of Cardio-Thoracic Surgery 2012;42:e58-65. CENTRAL [DOI: 10.1093/ejcts/ezs398]

Kafali 2004 {published data only}

Kafali H, Aldemir B, Kaygusuz K, Gürsoy S, Kunt N. Small-dose ketamine decreases postoperative morphine requirements. European Journal of Anaesthesiology 2004;21:914. CENTRAL

Kakinohana 2004 {published data only}

Kakinohana M, Huga Y, Sasara T, Saikawa A, Miyata Y, Tomiyama H, et al. Addition of ketamine to propofol-fentanyl anaesthesia can reduce post-operative pain and epidural analgesic consumption in upper abdominal surgery. Acute Pain 2004;5:75-9. CENTRAL [DOI: 0.1016/j.acpain.2003.12.001]

Kamal 2008 {published data only}

Kamal HM. Ketamine as an adjuvant to morphine for patient controlled analgesia in morbidly obese patients. Journal of Medical Sciences 2008;8(4):364-70. CENTRAL

Kapfer 2005 {published data only}

Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M. Nefopam and ketamine comparably enhance postoperative analgesia. Anesthesia & Analgesia 2005;100(1):169-74. CENTRAL [DOI: 10.1213/01.ANE.0000138037.19757.ED]

Karaman 2006 {published data only}

Karaman S, Kocabas S, Zincircioglu C, Firat V. Has ketamine preemptive analgesic effect in patients undergoing abdominal hysterectomy? [Abdominal histerektomi operasyonlarinda ketaminin preemptif analjezik etkisi var mi?]. The Journal of Turkish Society of Algology 2006;18(3):36-44. CENTRAL

Kararmaz 2003 {published data only}

Kararmaz A, Kaya S, Karaman H, Turhanoglu H, Ozyilmaz MA. Intraoperative intravenous ketamine in combination with epidural analgesia: postoperative analgesia after renal surgery. Anesthesia and Analgesia 2003;97:1092-6. CENTRAL [DOI: 10.1213/01.ANE.0000080205.24285.36]

Karcioglu 2013 {published data only}

Karcioglu M, Davarci I, Tuzcu K, Bozdogan YB, Turhanoglu S, Aydogan A, et al. Addition of ketamine to propofol-alfentanil anesthesia may reduce postoperative pain in laparoscopic cholecystectomy. Surgical Laparoscopy Endoscopy & Percutaneous Techniques 2013;23:197-202. CENTRAL [DOI: 10.1097/SLE.0b013e3182827f09]

Katz 2004 {published data only}

Katz J, Schmid R, Snijdelaar DG, Coderre TJ, McCartney CJL, Wowk A. Pre-emptive analgesia using intravenous fentanyl plus low-dose ketamine for radical prostatectomy under general anesthesia does not produce short-term or long-term reductions in pain or analgesic use. Pain 2004;110:707-18. CENTRAL [DOI: 10.1016/j.pain.2004.05.011]

Kim 2013 {published data only}

Kim SH, Kim SI, Ok SY, Park SY, Kim MG, Lee SJ et al. Opioid sparing effect of low dose ketamine in patients with intravenous patient-controlled analgesia using fentanyl after lumbar spinal fusion surgery. Korean Journal of Anesthesiology 2013;64(6):524-8. CENTRAL [DOI: 10.4097/kjae.2013.64.6.524]

Kim 2016 {published data only}

Kim DH, Choi JY, Ryu JH. Prospective, randomized, and controlled trial on ketamine infusion during bilateral axillo-breast approach (BABA) robotic or endoscopic thyroidectomy: effects on postoperative pain and recovery profiles. Medicine 2016;95(49):e5485. CENTRAL [DOI: 10.1097/MD.0000000000005485]

Köse 2012 {published data only}

Köse EA, Honca M, Akinci SB, Dal D, Aypar Ü. Efficacy of prophylactic ketamine in preventing postoperative shivering. Journal of Clinical and Analytical Medicine 2012;3(2):182-5. CENTRAL [DOI: 10.4328]

Kudoh 2002 {published data only}

Kudoh A, Takahira Y, Katagai H, Takazawa T. Small-dose ketamine improves the postoperative state of depressed patients. Anesthesia and Analgesia 2002;95:114-8. CENTRAL [DOI: 10.1213/01.ANE.0000020693.B7]

Kwok 2004 {published data only}

Kwok RFK, Lim J, Chan MTV, Gin T, Chiu WKY. Preoperative ketamine improves postoperative analgesia after gynecologic laparoscopic surgery. Anesthesia and Analgesia 2004;98:1044-9. CENTRAL [DOI: 10.1213/01.ANE.0000105911.66089.59]

Kwon 2009 {published data only}

Kwon OS, Lee HJ, Yoon JY, Kim CH, Kwon JY, Kim HK. Intraoperative low dose ketamine reduce postoperative pain after combined anesthesia with propofol and remifentanil in mastectomy patients. Korean Journal Anestesiology 2009;57(5):604-9. CENTRAL [DOI: 10.4097/kae.2009.57.5.604]

Lahtinen 2004 {published data only}

Lahtinen P, Kokki H, Hakala T, Hynynen M. S(+) -ketamine as an analgesic adjunct reduces opioid consumption after cardiac surgery. Anesthesia and Analgesia 2004;99:1295-301. CENTRAL [DOI: 10.1213/01.ANE.0000133913.07342.B9]

Lak 2010 {published data only}

Lak M, Foroozanmehr MJ, Ramazani MA, Araghizadeh H, Zahedi-Shoolami L. Assessment of ketamine effect as adjuvant to morphine in post-operative pain reduction in donor kidney transplanted. Iranian Red Crescent Medican Journal 2010;12(1):38-44. CENTRAL

Leal 2013 {published data only}

Leal PC, Sakata RK, Salomao R, Sadatsune EJ, Issy AM. Assessment of the effect of ketamine in combination with remifentanil on postoperative pain. Brazilian Journal of Anesthesiology 2013;63(2):178-82. CENTRAL

Leal 2015 {published data only}

Leal PC, Salomao R, Brunialti MKC, Sakata RK. Evaluation of the effect of ketamine on remifentanil-induced hyperalgesia: a double-blind, randomised study. Journal of Clinical Anesthesia 2015;27:331-7. CENTRAL [DOI: 10.1016/j.jclinane.2015.02.002]

Lebrun 2006 {published data only}

Lebrun T, Van Elstraete AC, Sandefo I, Polin B, Pierre-Louis L. Lack of a pre-emptive effect of low-dose ketamine on postoperative pain following oral surgery. Canadian Journal of Anesthesiology 2006;53(2):146-52. CENTRAL

Lee 2008 {published data only}

Lee EM, Lee H, Kim CH, Lee GY. A double-blinded, randomized, placebo controlled study of the effect a small dose of ketamine has on postoperative pain on sevoflurane-remifentanil anesthesia. Korean Journal of Anesthesiology 2008;54:146-51. CENTRAL

Lehmann 2001 {published data only}

Lehmann KA, Klaschik M. Lack of pre-emptive analgesic effect of low-dose ketamine in postoperative patients. A prospective, randomised doubleblind study [Klinische untersuchung über die präemptive analgesie durch niedrig dosiertes ketamin]. Schmerz 2001;15:248-53. CENTRAL

Lenzmeier 2008 {published data only}

Lenzmeier B, Moore RL, Cordts P, Garrett N. Menstrual cycle-related variations in postoperative analgesia with the preemptive use of N-methyl D-aspartate antagonist ketamine. Dimensions of Critical Care Nursing 2008;27(6):271-6. CENTRAL

Lin 2016 {published data only}

Lin H, Jia D. Effect of preemptive ketamine administration on postoperative visceral pain after gynecological laparoscopic surgery. Journal of Huazhong University of Science and Technology [Medical Sciences] 2016;36(4):584-7. CENTRAL [DOI: 10.1007/s11596-016-1629-0]

Lo 2008 {published data only}

Lo A, MacPherson N, Spiwak R. Prospective randomized trial of patient-controlled analgesia with ketamine and morphine or morphine alone after hysterectomy. Canadian Journal of Hospital Pharmacy 2008;61(5):334-9. CENTRAL

Loftus 2010 {published data only}

Loftus RW, Yeager MP, Clark JA, Brown JR, Abdu WA, Sengupta DK, et al. Intraoperative ketamine reduces perioperative opiate consumption in opiate-dependent patients with chronic back pain undergoing back surgery. Anesthesiology 2010;113:639-46. CENTRAL

Mahran 2015 {published data only}

Mahran E, Hassan ME. Comparison of pregabalin versus ketamine in postoperative pain management in breast cancer surgery. Saudi Journal of Anaesthesia 2015;9(3):253-7. CENTRAL [DOI: 10.4103/1658-354X.154X.154697]

Martinez 2014 {published data only}

Martinez V, Cymerman A, Ammar SB, Fiaud JF, Rapon C, Poindessous F, et al. The analgesic efficiency of combined pregabalin and ketamine for total hip arthroplasty: a randomised, double-blind, controlled study. Anaesthesia 2014;69:46-52. CENTRAL [DOI: 10.1111/anae.12495]

Mathisen 1999 {published data only}

Mathisen LC, Aasbo V, Raeder J. Lack of pre-emptive analgesic effect of (R)-ketamine in laparoscopic cholecystectomy. Acta Anaesthesiologica Scandinavica 1999;43:220-4. CENTRAL

McKay 2007 {published data only}

McKay WP, Donais P. Bowel function after bowel surgery: morphine with ketamine or placebo; a randomized controlled trial pilot study. Acta Anaesthesiologica Scandinavica 2007;51:1166-71. CENTRAL [DOI: 10.1111/j.1399-6576.2007.01436.x]

Mebazaa MS 2008 {published data only}

Mebazaa MS, Mestiri T, Kaabi B, Ben Ammar MS. Clinical benefits related to the combination of ketamine with morphine for patient controlled analgesia after major abdominal surgery [Benefices cliniques de l'association ketamine morphine en analgesie controlee par le patient apres chirurgie abdominale majeure]. La Tunisie Medicale 2008;86(5):435-40. CENTRAL

Mendola 2012 {published data only}

Mendola C, Cammarota G, Netto R, Cecci G, Pisterna A, Ferrante D et al. S(+) -ketamine for control of perioperative pain and prevention of post thoracotomy pain syndrome: a randomized, double-blind study. Minerva Anestesiologica 2012;78:757-66. CENTRAL

Menigaux 2000 {published data only}

Menigaux C, Fletcher D, Dupont X, Guignard B, Guirimand F, Chauvin M. The benefits of intraoperative small-dose ketamine on postoperative pain after anterior cruciate ligament repair. Anesthesia & Analgesia 2000;90:129-35. CENTRAL

Menigaux 2001 {published data only}

Menigaux C, Guignard B, Fletcher D, Sessler DI, Dupont X, Chauvin M. Intraoperative small-dose ketamine enhances analgesia after outpatient knee arthroscopy. Anesthesia and Analgesia 2001;93:606-12. CENTRAL

Michelet 2007 {published data only}

Michelet P, Guervilly C, Hélaine A, Avaro JP, Blayac D, Gaillat F, et al. Adding ketamine to morphine for patient-controlled analgesia after thoracic surgery: influence on morphine consumption, respiratory function, and nocturnal desaturation. British Journal of Anaesthesiology 2007;99(3):396-403. CENTRAL [DOI: 0.1093/bja/aem168]

Miziara 2016 {published data only}

Miziara LE, Simoni RF, Esteves LO, Cangiani LH, Grillo-Filho GFR, Paula AGL. Efficacy of continuous S(+)-ketamine infusion for postoperative pain control: a randomised placebo-controlled trial. Anesthesiology Research and Practice 2016;2016(Article ID 6918327):1-7. CENTRAL [DOI: 10.1155/2016/6918327]

Murdoch 2002 {published data only}

Murdoch CJ, Crooks BA, Miller CD. Effect of the addition of ketamine to morphine in patient-controlled analgesia. Anaesthesia 2002;57:484-8. CENTRAL [DOI: 10.1046/j.0003-2409.2001.02409.x]

Nesek‐Adam 2012 {published data only}

Nesek-Adam V, Grizelj-Stojcić, Mrsić V, Rasić Z, Schwartz D. Preemptive use of diclofenac in combination with ketamine in patients undergoing laparoscopic cholecystectomy: a randomized, double-blind, placebo-controlled study. Surgical Laparoscopy Endoscopy & Percutaneous Techniques 2012;22(3):232-8. CENTRAL

Nielsen 2017 {published data only}

Nielsen RV, Fomsgaard JS, Siegel H, Martusevicius R, Nikolajsen L, Dahl JB, et al. Intraoperative ketamine reduces immediate postoperative opioid consumption after spinal fusion surgery in chronic pain patients with opioid dependency: a randomized, blinded trial. Pain 2017;158(3):463-70. CENTRAL [DOI: 10.1097/j.pain.0000000000000782]

Ögün 2001 {published data only}

Ögun CÖ, Duman A, Ökesli S. The comparison of postoperative analgesic effects of preemptive ketamine and fentanyl use in mastectomy operations. The Journal of the Turkish Society of Algology 2001;13(2):31-40. CENTRAL

Ong 2001 {published data only}

Ong EL, Osborne GA. Ketamine for co-induction of anaesthesia in oral surgery. Ambulatory Surgery 2001;9:131-5. CENTRAL

Ozhan 2013 {published data only}

Ozhan Y, Bakan N, Karaoren GY, Tomruk SG, Topac Z. Effects of subanesthetic ketamine on pain and cognitive functions on TIVA [TIVA'da subanestezik ketaminin agri ve kognitif fonksiyonlara etkisi]. Journal of Clinical and Analytical Medicine 2015;6(4):452-7. CENTRAL [DOI: 10.4328/JCAM.2161]

Pacreu 2012 {published data only}

Pacreu S, Fernández Candil J, Moltó L, Carazo J, Fernández Galinski S. The perioperative combination of methadone and ketamine reduces post-operative opioid usage compared with methadone alone. Acta Anaesthesiologica Scandinavica 2012;56:1250-6. CENTRAL [DOI: 10.1111/j.1399-6576.2012.02743.x]

Papaziogas 2001 {published data only}

Papaziogas B, Argiriadou H, Papagiannopoulou P, Pavlidis T, Georgiou M, Sfyra M, et al. Preincisional intravenous low-dose ketamine and local infiltration with ropivacaine reduces postoperative pain after laparoscopic cholecystectomy. Surgical Endoscopy 2001;15:1030-3. CENTRAL [DOI: I0.1007/s004640090124]

Parikh 2011 {published data only}

Parikh B, Maliwad J, Shah VR. Preventive analgesia: effect of small dose of ketamine on morphine requirement after renal surgery. Journal of Anaesthesiology Clinical Pharmacology 2011;27(4):485-8. CENTRAL

Patel 2016 {published data only}

Patel J, Thosani R, Kothari J, Garg P, Pandya H. Clonidine and ketamine for stable hemodynamics in off-pump coronary artery bypass. Asian Cardiovascular & Thoracic Annals 2016;24(7):638-46. CENTRAL [DOI: 10.1177/0218492316663359]

Pirim 2006 {published data only}

Pirim A, Karaman S, Uyar M, Certug A. Addition of ketamine infusion to patient controlled analgesia with intravenous morphine after abdominal hysterectomy. The Journal of the Turkish Society of Algology 2006;18(1):52-8. CENTRAL

Remérand 2009 {published data only}

Remérand F, Le Tendre C, Baud A, Couvret C, Pourrat X, Favard L, et al. The early and delayed analgesic effects of ketamine after total hip arthroplasty: a prospective, randomized, controlled, double-blind study. Pain Medicine 2009;109(6):1963-71. CENTRAL [DOI: 10.1213/ANE.0b013e3181bdc8a0]

Reza 2010 {published data only}

Reza FM, Zahra F, Esmaeel F, Hossein A. Preemptive analgesic effect of ketamine in patients undergoing elective cesarean section. The Clinical Journal of Pain 2010;26(3):223-6. CENTRAL

Roytblat 1993 {published data only}

Roytblat L, Korotkoruthko A, Katz J, Glazer M, Greemberg L, Fisher A. Postoperative pain: the effect of low-dose ketamine in addition to general anesthesia. Regional Anesthesia and Pain Management 1993;77:1161-5. CENTRAL

Safavi 2011 {published data only}

Safavi M, Honarmand A, Nematollahy Z. Pre-incisional analgesia with intravenous or subcutaneous infiltration of ketamine reduces postoperative pain in patients after open cholecystectomy: a randomized, double-blind, placebo-controlled study. Pain Medicine 2011;12:1418-26. CENTRAL

Sahin 2004 {published data only}

Sahin A, Canbay O, Cuhadar A, Celebi N, Aypar U. Bolus ketamine does not decrease hyperalgesia after remifentanil infusion. The Pain Clinic 2004;16(4):407-11. CENTRAL

Sen 2009 {published data only}

Sen H, Sizlan A, Yanarates O, Emirkadi H, Ozkan S, Dagli G, et al. A comparison of gabapentin and ketamine in acute and chronic pain after hysterectomy. Pain Medicine 2009;109(5):1645-50. CENTRAL [DOI: 10.1213/ANE.0b013e3181b65ea0]

Siddiqui 2015 {published data only}

Siddiqui KM, Khan FA. Effect of preinduction low-dose ketamine on intraoperative and immediate postoperative analgesia requirement in day care surgery: a randomized controlled trial. Saudi Journal of Anaesthesia 2015;9(4):422-7. CENTRAL [DOI: 10.4103/1658-354X.159468]

Singh 2013 {published data only}

Singh H, Kundra S, Singh RM, Grewal A, Kaul TK, Sood D. Preemptive analgesia with ketamine for laparoscopic cholecystectomy. Journal of Anaesthesiology Clinical Pharmacology 2013;29(4):478-84. CENTRAL [DOI: 10.4103/0970-9185.119141]

Snijdelaar 2004 {published data only}

Snijdelaar DG, Cornelisse HB, Schmid RL, Katz J. A randomised, controlled study of peri-operative low dose S(+) -ketamine in combination with postoperative patient-controlled S(+) -ketamine and morphine after radical prostatectomy. Anaesthesia 2004;59:222-8. CENTRAL

Song 2013 {published data only}

Song JW, Kim JK, Song Y, Yang SY, Park SJ, Kwak YL. Effect of ketamine as an adjunct to intravenous patient-controlled analgesia, in patients at high risk of postoperative nausea and vomiting undergoing lumbar spinal surgery. British Journal of Anaesthesia 2013;111(4):630-5. CENTRAL [DOI: 10.1093/bja/aet192]

Song 2014 {published data only}

Song YK, Lee C, Seo DH, Park SN, Moon SY, Park CH. Interaction between postoperative shivering and hyperalgesia caused by high-dose remifentanil. Korean Journal of Anesthesiology 2014;66(1):44-51. CENTRAL [DOI: 10.4097/kjae.2014.66.1.44]

Spreng 2010 {published data only}

Spreng UJ, Dahl V, Raeder J. Effects of perioperative S(+) ketamine infusion added to multimodal analgesia undergoing ambulatory haemorrhoidectomy. Scandinavian Journal of Pain 2010;1:100-5. CENTRAL [DOI: 10.1016/j.sjpain.2010.01.009]

Stubhaug 1997 {published data only}

Stubhaug A, Breivik H, Eide PK, Kreunen M, Foss A. Mapping of punctuate hyperalgesia around a surgical incision demonstrates that ketamine is a powerful suppressor of central sensitization to pain following surgery. Acta Anaesthesiologica Scandinavica 1997;41:1124-32. CENTRAL [DOI: 10.1111/j.1399-6576.1997.tb04854.x]

Subramaniam 2011 {published data only}

Subramaniam K, Akhouri V, Glazer PA, Rachlin J, Kunze L, Cronin M, et al. Intra- and postoperative very low dose intravenous ketamine infusion does not increase pain relief after major spine surgery in patients with preoperative narcotic analgesic intake. Pain Medicine 2011;12:1276-83. CENTRAL

Suzuki 1999 {published data only}

Suzuki M, Tsueda K, Lansing PS, Tolan MM, Fuhrman TM, Ignacio CI, et al. Small-dose ketamine enhances morphine-induced analgesia after outpatient surgery. Anesthesia and Analgesia 1999;89:98-103. CENTRAL

Suzuki 2006 {published data only}

Suzuki M, Haraguti S, Sugimoto K, Kikutani T, Shimada Y, Sakamoto A. Low-dose intravenous ketamine potentiates epidural analgesia after thoracotomy. Anesthesiology 2006;105:111-9. CENTRAL

Tena 2014 {published data only}

Tena B, Gomar C, Rios J. Perioperative epidural or intravenous ketamine does not improve the effectiveness of thoracic epidural analgesia for acute and chronic pain after thoracotomy. Clinical Journal of Pain 2014;30(6):490-500. CENTRAL

Ünlügenc 2003 {published data only}

Ünlügenc H, Özalevi M, Güler T, Isik G. Postoperative pain management with intravenous patient-controlled morphine: comparison of the effect of adding magnesium or ketamine. European Journal of Anaesthesiology 2003;20:416-21. CENTRAL

Van Elstraete 2004 {published data only}

Van Elstraete AC, Lebrun T, Sandefi I, Polin B. Ketamine does not decrease postoperative pain after remifentanil-based anaesthesia for tonsillectomy in adults. Acta Anaesthesiologica Scandinavica 2004;48:756-60. CENTRAL [DOI: 10.1111/j.1399-6576.2004.00399.x]

Webb 2007 {published data only}

Webb AR, Skinner BS, Leong S, Kolawole H, Crofts T, Taverner M, et al. The addition of a small-dose ketamine infusion to tramadol for postoperative analgesia: a double-blinded, placebo-controlled, randomized trial after abdominal surgery. Pain Medicine 2007;104(4):912-7. CENTRAL [DOI: 10.1213/01.ane.0000256961.01813.da]

Woo 2014 {published data only}

Woo JH, Kim YJ, Baik HJ, Han JI, Chung RH. Does intravenous ketamine enhance analgesia after arthroscopic shoulder surgery with ultrasound guided single-injection interscalene block? a randomized, prospective, double-blind trial. Journal of Korean Medical Science 2014;29:1001-6. CENTRAL [DOI: 10.3346/jkms.2014.29.7.1001]

Wu 2009 {published data only}

Wu Y, Li H, Xiong J, Xu Z, Ma L, Huang X, et al. Effects of patient-controlled analgesia with small dose ketamine combined with morphine and the influence thereof on plasma beta-endorphin level in patients after radical operation for esophageal carcinoma. Journal of the Chinese Medical Association 2009;89(5):314-7. CENTRAL

Yalcin 2012 {published data only}

Yalcin N, Uzun ST, Reisli R, Borazan H, Otelcioglu S. A comparison of ketamine and paracetamol for preventing remifentanil induced hyperalgesia in patients undergoing total abdominal hysterectomy. International Journal of Medical Sciences 2012;9:327-33. CENTRAL [DOI: 10.7150/ijms.4222]

Yamauchi 2008 {published data only}

Yamauchi M, Asano M, Watanabe M, Iwasaki S, Furuse S, Namiki A. Continuous low-dose ketamine improves the analgesic effects of fentanyl patient-controlled analgesia after cervical spine surgery. Anesthesia and Analgesia 2008;107(3):1041-4. CENTRAL [DOI: 10.1213/ane.0b013e31817f1e4a]

Yazigi 2012 {published data only}

Yazigi A, Abou-Zeid H, Srouji T, Madi-Jebara S, Haddad F, Jabbour K. The effects of low-dose intravenous ketamine on continuous intercostal analgesia following thoracotomy. Annals of Cardiac Anaesthesia 2012;15(1):32-8. CENTRAL

Yeom 2012 {published data only}

Yeom JH, Chon MS, Jeon WJ, Shim JH. Peri-operative ketamine with the ambulatory elastometric infusion pump as an adjuvant to manage acute postoperative pain after spinal fusion in adults: a prospective randomized trial. Korean Journal of Anesthesiology 2012;63(1):54-8. CENTRAL [DOI: 10.4097/kjae.2012.63.1.54]

Ysasi 2010 {published data only}

Ysasi A, Calderón E, Wendt T, Gracia T, Torres LM, Llorens R. Efficacy of low doses of ketamine in postoperative analgesia and the use of morphine after myocardial revascularisation surgery [Efecto de dosis bajas de ketamine en la analgesia postoperatoria y consumo de morfina tras cirurgía de revascularizatión miocárdica]. Revista de la Sociedad Espanola del Dolor 2010;17(4):190-5. CENTRAL [DOI: 10.1016/j.resed.2010.04.002]

Zakine 2008 {published data only}

Zakine J, Samarcq D, Lorne E, Moubarak M, Montravers P, Beloucif S, et al. Postoperative ketamine administration decreases morphine consumption in major abdominal surgery. A prospective, randomized, double-blind, controlled study. Pain Medicine 2008;106:1856-61. CENTRAL [DOI: 10.1213/ane.0b013e3181732776]

Referencias de los estudios excluidos de esta revisión

Ir a:

Abrishamkar 2012 {published data only}

Abrishamkar S, Eshraghi N, Feizi A, Talakoub R, Rafiei A, Rahmani P. Analgesic effects of ketamine infusion on postoperative pain after fusion and instrumentation of the lumbar spine: a prospective randomized clinical trial. Medical Archives 2012;66(2):107-10. CENTRAL

Adams 2003 {published data only}

Adams Ha, Meyer H, Stoppa A, Müller-Goch A, Bayer P, Hecker H. Anaesthesia for caesarean section. Comparison of two general anaesthetic regimens and spinal anaesthesia [Anästhesie zur Sectio caesarea. Ein Vergleich von zwei Verfahren der Allgemeinanästhesie sowie der Spinalanästhesie]. Anaesthesist 2003;52:23-32. CENTRAL [DOI: 10.1007/s00101-002-0440-4]

Aghamohammadi 2012 {published data only}

Aghamohammadi D, Hosseinzadeh H, Eidy M, Vizhe ZM, Fakhri MBA, Movassagi R, et al. Multimodal preincisional premedication to prevent acute pain after cholecystectomy. Journal of Cardiovascular and Thoracic Research 2012;4(3):65-8. CENTRAL [DOI: 10.5681/jcvtr.2012.016]

Akca 2016 {published data only}

Acka B, Aydogan-Eren E, Canbay Ö, Karagöz AH, Ûzümcügil F, Ankay-Yilbas A, et al. Comparison of efficacy of prophylactic ketamine and dexmedetomidine on postoperative bladder catheter-related discomfort. Saudi Medical Journal 2016;37(1):55-9. CENTRAL [DOI: 10.15537/smj.2016.1.14122]

Avidan 2017 {published data only}

Avidan MS, Maybrier HR, Abdallah AB, Jacobsohn E, Vlisides PE, Pryor KO, et al. Intraoperative ketamine for prevention of postoperative delirium or pain after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial. Lancet 2017;390:267-75. CENTRAL [DOI: 10.1016/S0140-6736(17)31467-8]

Behdad 2011 {published data only}

Behdad A, Hosseinpour M, Khorasani P. Preemptive use of ketamine on post operative pain of appendectomy. Korean Journal of Pain 2011;24(3):137-40. CENTRAL [DOI: 10.3344/kjp.2011.24.3.137]

Bentley 2005 {published data only}

Bentley MW, Stas JM, Johnson JM, Viet BC, Garrett N. Effects of preincisional ketamine treatment on natural killer cell activity and postoperative pain management after oral maxillofacial surgery. American Association of Nurse Anesthetists 2005;73(6):427-36. CENTRAL

Bilgin 2005 {published data only}

Bilgin H, Özcan B, Bilgin T, Kerimoglu B, Uckunkaya N, Toker A, et al. The influence of timing of systemic ketamine administration on postoperative morphine consumption. Journal of Clinical Anesthesia 2005;17:592-7. CENTRAL [DOI: 10.1016/j.jclinane.2005.04.005]

Clausen 1975 {published data only}

Clausen L, Sinclair DM, Van Hasselt CH. Intravenous ketamine for postoperative analgesia. South African Medical Journal 1975;49(35):1437-40. CENTRAL

Edwards 1993 {published data only}

Edwards ND, Fletcher A, Cole JR, Peacock JE. Combined infusions of morphine and ketamine for postoperative pain in elderly patients. Anaesthesia 1993;48:124-7. CENTRAL [DOI: 10.1111/j.1365-2044.1993.tb06849.x]

Gillies 2007 {published data only}

Gillies A, Lindholm D, Angliss M, Orr A. The use of ketamine as rescue analgesia in the recovery room following morphine administration -a double-blind randomised controlled trial in postoperative patients. Anaesthesia and Intensive Care 2007;35(2):199-203. CENTRAL

Guan 2008 {published data only}

Guan JQ, Gan XL, Hei ZQ, Gao WL, Cai J. Effects of ketamine on analgesia of morphine and levels of cell factors in colorectal cancer. Chinese Journal of New Drugs 2008;17(18):1615-8. CENTRAL

Heinke 1999 {published data only}

Heinke W, Grimm D. Preemptive effects caused by co-analgesia with ketamine in gynecological laparotomies? Anaesthesiologie und Reanimation 1999;24(3):60-4. CENTRAL

Hong 2011 {published data only}

Hong BH, Lee WY, Kim YH, Yoon SH, Lee WH. Effects of intraoperative low dose ketamine on remifentanil-induced hyperalgesia in gynecologic surgery with sevoflurane anesthesia. Korean Journal of Anesthesiology 2011;61(3):238-43. CENTRAL [DOI: 10.4097/kjae.2011.61.3.238]

Ito 1974 {published data only}

Ito Y, Ichiyanagi K. Post-operative pain relief with ketamine infusion. Anaesthesia 1974;29:222-9. CENTRAL

Jahangir 1993 {published data only}

Jahangir SM, Islam M, Aziz L. Ketamine infusion for postoperative analgesia in asthmatics: a comparison with intermittent meperidine. Anesthesia and Analgesia 1993;76:45-9. CENTRAL

Jensen 2008 {published data only}

Jensen LL, Handberg G, Helbo-Hansen HS, Skaarup I, Munk T, Lund N. No morphine sparing effect of ketamine added to morphine for patient-controlled intraveous analgesia after uterine artery embolization. Acta Anaesthesiologica Scandinavica 2008;52:479-86. CENTRAL [DOI: 10.1111/j.1399-6576.2008.01602.x]

Jiang 2016 {published data only}

Jiang M, Wang MH, Wang XB, Liu L, Wu JL, Yang XL et al. Effect of intraoperative application of ketamine on postoperative depressed mood on patients undergoing elective orthopedic surgery. Journal of Anesthesia 2016;30:232-7. CENTRAL [DOI: 10.1007/s00540-015-2096-7]

Joachimmson 1986 {published data only}

Joachimmsson PO, Hedstrand U, Eklund A. Low-dose ketamine infusion for analgesia during postoperative ventilator treatment. Acta Anaesthesiologica Scandinavica 1986;30(8):697-702. CENTRAL [DOI: 10.1111/j.1399-6576.1986.tb02505.x]

Kadic 2016 {published data only}

Kadic L, Van Haren FG, Wilder-Smith O, Bruhn J, Driessen JJ, De Waal Malefijt MC. The effect of pregabalin and S-ketamine in total knee arthroplasty patients: a randomized study. Journal of Anaesthesiology Clinical Pharmacology 2016;32(4):476-82. CENTRAL [DOI: 10.4103/0970-9185.194762]

Kim 2001 {published data only}

Kim CJ, Chea JS, Chung MY, Song DH, Park JJ, Lee BH. The analgesic effect of combined infusions of morphine and ketamine using an intravenous PCA after a cesarean section. Korean Journal of Anesthesiology 2001;40:509-14. CENTRAL [DOI: 10.4097/kjae.2001.40.4.509]

Kim 2005 {published data only}

Kim YJ, Baik HJ, Kim JH. The effects of the intravenous continuous infusion of low-dose ketamine on postoperative pain after total intravenous anesthesia. Korean Journal of Anesthesiology 2005;48:163-70. CENTRAL [DOI: 10.4097/kjae.2005.48.2.163]

Kollender 2008 {published data only}

Kollender Y, Bickels J, Stocki D, Maruoani N, Chazan S, Nirkin A, et al. Subanaesthetic ketamine spares postoperative morphine and controls pain better than standard morphine does alone in orthopaedic-oncological patients. European Journal of Cancer 2008;44:954-62. CENTRAL [DOI: 10.1016/j.ejca.2008.02.021]

Kose 2008 {published data only}

Kose EA, Dal D, Akinci SB, Saricaoglu F, Aypar U. The efficacy of ketamine for the treatment of postoperative shivering. Anesthesia and Analgesia 2008;106(1):120-2. CENTRAL [DOI: 10.1213/01.ane.0000296458.16313.7c]

Launo 2004 {published data only}

Launo C, Bassi C, Spagnolo L, Badano S, Ricci C, Lizzi A, et al. Preemptive ketamine during general anesthesia for postoperative analgesia in patients undergoing laparoscopic cholecystectomy. Minerva Anestesiologica 2004;70:727-38. CENTRAL

Lee 2005 {published data only}

Lee HD, Kim HK, Lee SN, Lee SY, Lee JH, Park DH. The effect of low dose i.v. ketamine in combination with epidural morphine on postoperative pain. Korean Journal of Anesthesiology 2005;49:81-5. CENTRAL [DOI: 10.4097/kjae.2005.49.1.81]

Lee 2006 {published data only}

Lee YS, Kim WY, Cha MH, Kim JH, Kim JH, Park YC, et al. Effects of preincisional ketamine on postoperative pain after laparoscopic assisted vaginal hysterectomy. Anesthesia and Pain Medicine 2006;1:44-7. CENTRAL

Lee 2013 {published data only}

Lee W, Shin D, Cho K, Kim MH. Comparison of dexmedetomidine and ketamine for the analgesic effect using intravenous patient-controlled analgesia after gynecological abdominal surgery. Korean Journal of Anesthesiology 2013;65(6 Suppl):S132-4. CENTRAL [DOI: 10.4097/kjae.2013.65.6S.S132]

Lee 2014 {published data only}

Lee MH, Chung MH, Han CS, Lee JH, Choi YR, Choi EM, et al. Comparison of effects of intraoperative esmolol and ketamine infusion on acute postoperative pain after remifentanil-based anesthesia in patients undergoing laparoscopic cholecystectomy. Korean Journal of Anesthesia 2014;66(3):222-9. CENTRAL [DOI: 10.4097/kjae.2014.66.3.222]

Liang 2006 {published data only}

Liang S, Chen Y, Lin C. Low-dose ketamine combined with fentanyl for intravenous postoperative analgesia in elderly patients. Journal of Southern Medical University 2006;26(11):1663-4. CENTRAL

Lux 2009 {published data only}

Lux EA, Hinrichs T, Mathejka E, Wilhelm W. Ketamine racemate and fast track anaesthesia: influence on recovery times and postoperative opioid needs [Ketaminrazemat bei "fast-track" -anästhesie. Einfluss auf aufwachzeiten und postoperativen opioidbedarf]. Anaesthesist 2009;58(10):1027-34. CENTRAL [DOI: 10.1007/s00101-009-1607-z]

Malek 2006 {published data only}

Malek J, Kurzová A, Bendová M, Nosková P, Strunová M, Vedral T. The prospective study on the effect of a preemptive long-term postoperative administration of a low-dose ketamine on the incidence of chronic post-mastectomy pain [Efekt perioperacního podávání ketaminu na potlacení vzniku chronické bolesti po operaci prsu -prospktivní studie]. Anestesziologie a intevzivní medicína 2006;17:34-7. CENTRAL

Maurset 1989 {published data only}

Maurset A, Skoglund LA, Hustveit O, Oye I. Comparison of ketamine and pethidine in experimental and postoperative pain. Pain 1989;36:37-41. CENTRAL [DOI: 10.1016/0304-3959(89)90109-7]

Nayar 2009 {published data only}

Nayar R, Sahajanand H. Does anesthetic induction for Cesarean section with a combination of ketamine and thiopentone confer any benefits over thiopentone or ketamine alone? A prospective randomized study. Minerva Anestesiologica 2009;75(4):185-90. CENTRAL

Ndoye 2008 {published data only}

NDoye Diop M, Khalil Y, Diatta B, Seck M, Ndiaye M, Niang B, et al. Prevention of the acute tolerance with opioids by ketamine [Prevention de la tolerance aigue au fentanyl par la ketamine a faible poids]. Dakar Medical Journal 2008;53(2):122-6. CENTRAL

Nesher 2008 {published data only}

Nesher N, Serovian I, Marouani N, Chazan S, Weinbroum AA. Ketamine spares morphine consumption after transthoracic lung and heart surgery without adverse effects. Pharmacological Research 2008;58:38-44. CENTRAL [DOI: 10.1016/j.phrs.2008.06.003]

Nesher 2009 {published data only}

Nesher N, Eksterin MP, Paz Y, Marouani N, Chazan S, Weinbroum AA. Morphine with adjuvant ketamine vs higher dose of morphine alone for immediate postthoracotomy analgesia. Chest 2009;136(1):245-52. CENTRAL [DOI: 10.1378/chest.08-0246]

Nikolayev 2008 {published data only}

Nikolayev AP, Nikoda VV, Svetlov VA. Multimodal approach to postoperative analgesia in patients with neuropathic pain. Anesteziologiia i Reanimatologiia 2008;5:99-103. CENTRAL

Nitta 2013 {published data only}

Nitta R, Goyagi T, Nishikawa T. Combination of oral clonidine and intravenous low-dose ketamine reduces the consumption of postoperative patient-controlled analgesia morphine after spine surgery. Acta Anaesthesiologica Taiwanica 2013;51:14-7. CENTRAL [DOI: 10.1016/j.aat.2013.03.003]

Nourozi 2010 {published data only}

Nourozi A, Talebi H, Fateh S, Mohammadzadeh A, Eghtesadi-Araghi P, Ahmadi Z, et al. Effect of adding ketamine to pethidine on postoperative pain in patients undergoing major abdominal operations: double blind randomized controlled trial. Pakistan Journal of Biological Sciences 2010;13(24):1214-8. CENTRAL [DOI: 10.3923/pjbs.2010.1214.1218]

Oliveira 2005 {published data only}

Oliveira CMB, Issy AM, Sakata RK, Garcia JBS, Martins CR. Preemptive effect of IV S(+) -ketamine for hysterectomy. Acute Pain 2005;7:139-43. CENTRAL [DOI: 10.1016/j.acpain.2005.08.001]

Owen 1987 {published data only}

Owen H, Reekie RM, Clements JA, Watson R, Nimmo WS. Analgesia from morphine and ketamine. Anaesthesia 1987;42:1051-6. CENTRAL [DOI: 10.1111/j.1365-2044.1987.tb05167.x]

Park 2004 {published data only}

Park HJ, Kim ST. The effect of intravenous ketamine on the recovery from total intravenous anesthesia with propofol. Korean Journal of Anesthesiology 2004;46(5):517-23. CENTRAL [DOI: 10.4097/kjae.2004.46.5.517]

Perrin 2009 {published data only}

Perrin SB, Purcell AN. Intraoperative ketamine may influence persistent pain following knee arthroplasty under combined general and spinal anaesthesia: a pilot study. Anaesthesia and Intensive Care 2009;37(2):248-53. CENTRAL

Reeves 2001 {published data only}

Reeves M, Lindholm DE, Myles PE, Fletcher H, Hunt JO. Adding ketamine to morphine for patient-controlled analgesia after major abdominal surgery: a double-blinded, randomized, controlled trial. Anesthesia and Analgesia 2001;93:116-20. CENTRAL [DOI: 10.1097/00000539-200107000-00025]

Sadove 1971 {published data only}

Sadove MS, Shulman M, Hatano S, Fevold N. Analgesic effects of ketamine administered in subdissociative doses. Anesthesia and Analgesia 1971;50(3):452-7. CENTRAL

Sollazzi 2008 {published data only}

Sollazzi L, Modesti C, Vitale F, Sacco T, Ciocchetti P, Idra AS, et al. Preinductive use of clonidine and ketamine improves recovery and reduces postoperative pain after bariatric surgery. Surgery for Obesity and Related Diseases 2009;5:67-71. CENTRAL [DOI: 10.1016/j.soard.2008.09.018]

Song 2004 {published data only}

Song X, Li X, Zhao H, Yang T, Wang F. Pre-emptive analgesia effects of ketamine on postoperative pain management and stress responses. Journal of Jilin University (Medicine Edition) 2004;30(4):605-7. CENTRAL

Sveticic 2008 {published data only}

Sveticic G, Farzanegan F, Zmoos P, Zmoos S, Eichenberger U, Curatolo M. Is the combination of morphine with ketamine better than morphine alone for postoperative intravenous patient-controlled analgesia. Anesthesia and Analgesia 2008;106(1):287-93. CENTRAL [DOI: 10.1213/01.ane.0000289637.11065.8f]

Talu 2002 {published data only}

Talu Gk, Özyacin S, Dereli N, Sentürk M, Yücel A. The effect of ketamine administered preoperatively through different routes on thoracotomy pain: a randomized, double blind, placebo controlled study [Torakotomi Agrisinda preoperatif farkli yollardan uygulanan ketaminin etkinligi: randomize, cift kör, plasebo kontrollü klinik calisma]. Journal of Turkish Society of Algology 2002;14(2):54-9. CENTRAL

Thomas 2012 {published data only}

Thomas M, Tennant I, Augier R, Gordon-Strachan G, Harding H. The role of pre-induction ketamine in the management of postoperative pain in patients undergoing elective gynaecological surgery at the university hospital of the West Indies. West Indian Medical Journal 2012;61(3):224-9. CENTRAL

Tverskoy 1994 {published data only}

Tverskoy M, Ozy Y, Isakson A, Finger J, Bradley EL Jr, Kissin I. Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesthesia and Analgesia 1994;78(2):205-9. CENTRAL

Tverskoy 1996 {published data only}

Tverskoy M, Oren M, Vaskovich M, Dashakovsky I, Kissin I. Ketamine enhances local anesthetic and analgesic effects of bupivacaine by peripheral mechanism: a study in postoperative patients. Neuroscience Letters 1996;215:5-8. CENTRAL [DOI: 10.1016/S0304-3940(96)12922-0]

Ünlügenc 2002 {published data only}

Ünlügenc H, Gündüz M, Özalevli M, Akman H. A comparative study on the analgesic effect of tramadol, tramadol plus magnesium, and tramadol plus ketamine for postoperative pain management after major abdominal surgery. Acta Anaesthesiologica Scandinavica 2002;46:1025-30. CENTRAL

Urban 2008 {published data only}

Urban MK, Deau JTY, Wukovits B, Lipnistky JY. Ketamine as an adjunct to postoperative pain management in opioid tolerant patients after spinal fusions: a prospective randomized trial. Hospital for Special Surgery Journal 2008;4(1):62-5. CENTRAL [DOI: 10.1007/s11420-007-9069-9]

Weinbroum 2003 {published data only}

Weinbroum AA. A single small dose of postoperative ketamine provides rapid and sustained improvement in morphine analgesia in the presence of morphine-resistant pain. Anesthesia and Analgesia 2003;96:879-95. CENTRAL [DOI: 10.1213/01.ANE.0000048088.17761.B4]

Wilder‐Smith 1998 {published data only}

Wilder-Smith OHG, Arendt-Nielsen L, Gäumann D, Tassonyi E, Rifat KR. Sensory changes and pain after abdominal hysterectomy: a comparison of anesthetic supplementation with fentanyl versus magnesium or ketamine. Anesthesia and Analgesia 1998;86:95-101. CENTRAL [DOI: 10.1213/00000539-199801000-00019]

Xie 2003 {published data only}

Xie H, Wang X, Liu G, Wang G. Analgesic effects and pharmacokinetics of a low dose of ketamine preoperatively administered epidurally or intravenously. Clinical Journal of Pain 2003;19:317-22. CENTRAL

Xu 2017 {published data only}

Xu Y, Li Y, Huang X, Chen D, She B, Ma D. Single bolus low-dose of ketamine does not prevent postpartum depression: a randomized, double-blind, placebo-controlled, prospective trial. Archives of Gynecology and Obstetrics 2017;295:1167-74. CENTRAL [DOI: 10.1007/s00404-017-4334-8]

Referencias de los estudios en espera de evaluación

Ir a:

Lee 2018 {published data only}

Lee J, Park HP, Jeong MH, Song JD, Kim HC. Efficacy of ketamine for postoperative pain following robotic thyroidectomy: A prospective randomised study. Journal of International Medical Research 2018;46(3):1109-20. CENTRAL

Lou 2017 {published data only}

Lou QB, Nan K, Xiang FF, Zhu WS, Zhang XT, Li J. Effect of perioperative multi-day low-dose ketamine infusion on prevention of postmastectomy pain syndrome. National Medical Journal of China 2017;97(46):3636-41. CENTRAL

Moon 2018 {published data only}

Moon YE, Kim MH, Lee HM, Yoon HM, Jeon YH. Preventative effect of ketamine on postsurgical hyperalgesia induced at a body part remote from the surgical site. Minerva Anestesiologica 2018;84(4):481-7. CENTRAL

AlBalawi 2013

AlBalawi Z, McAlister FA, Thorlund K, Wong M, Wetterslev J. Random error in cardiovascular meta-analyses: how common are false positive and false negative results? International Journal of Cardiology 2013;168(2):1102-7. [DOI: 10.1016/j.ijcard.2012.11.048]

Anderson 2001

Anderson R, Saiers JH, Abram S, Schlict C. Accuracy in equianalgesic dosing: conversion dilemmas. Journal of Pain and Symptom Management 2001;21(5):397-406. [DOI: 10.1016/S0885-3924(01)00271-8]

Angst 2006

Angst MS, Clark JD. Opioid-induced hyperalgesia. A qualitative systematic review. Anesthesiology 2006;104(3):570-87.

Arendt‐Nielsen 1996

Arendt-Nielsen L, Nielsen J, Petersen-Felix S, Schnider TW, Zbinden AM. Effect of racemic mixture and the (S+) isomer of ketamine on temporal and spatial summation of pain. British Journal of Anaesthesia 1996;77:625-31. [DOI: 10.1093/bja/77.5.625]

Aroni 2009

Aroni F, Iacovidou N, Dontas I, Pourzotaki C, Xanthos T. Pharmacological aspects and potential new clinical applications of ketamine: reevaluation of an old drug. Journal of Clinical Pharmacology 2009;49:957-64. [DOI: 10.1177/0091270009337941]

Beals 2003

Beals JK, Carter LB, Jevtovic-Todorovic V. Neurotoxicity of nitrous oxide and ketamine is more severe in aged than in young rat brain. Annals of the New York Academy of Sciences 2003;993:115; discussion 123-4. [DOI: 10.1111/j.1749-6632.2003.tb07518.x]

Begon 2001

Begon S, Pickering G, Eschalier A, Mazur A, Rayssiguier Y, Dubray C. Role of spinal NMDA receptors, protein kinase C and nitric oxide synthase in the hyperalgesia induced by magnesium deficiency in rats. British Journal of Pharmacology 2001;134:1227-36. [DOI: 10.1038/sj.bjp.0704354]

Bell 2017

Bell RF, Eccleston C, Kalso EA. Ketamine as an adjuvant to opioids for cancer pain. Cochrane Database of Systematic Reviews 2017, Issue 6. Art. No: CD003351. [DOI: 10.1002/14651858.CD003351.pub3]

Benarroch 2013

Benarroch EE. HCN channels: function and clinical implications. Neurology 2013;80:304-10.

Bredlaw 2013

Bredlaw AL, Thakur R, Korones DN, Dworkin RH. Ketamine for pain in adults and children with cancer; a systematic review and synthesis of the literature. Pain Medicine 2013;14(10):1505-17. [DOI: 10.1111/pme.12182]

Bulutcu 2002

Bulutcu F, Dogrul A, Oguz Güc M. The involvement of nitric oxide in the analgesic effects of ketamine. Life Sciences 2002;71:841-53. [DOI: 10.1016/S0024-3205(02)01765-4]

Chen 2009

Chen X, Shu S, Bayliss DA. HCN1 channel subunits are a molecular substrate for hypnotic actions of ketamine. Journal of Neuroscience 2009;29(3):600-9. [DOI: 10.1523/JNEUROSCI.3481-08.2009]

Collins 1997

Collins SL, Moore RA, McQuay HJ. The visual analogue pain intensity scale: what is moderate pain in millimetres? Pain 1997;72(1-2):95-7. [DOI: 10.1016/S0304-3959(97)00005-5]

Colvin 2010

Colvin LA, Fallon MT. Opioid-induced hyperalgesia: a clinical challenge. British Journal of Anaesthesia 2010;104(2):125-7. [DOI: 10.1093/bja/aep392]

Dechartres 2013

Dechartres A, Trinquart L, Boutron I, Ravaud P. Influence of trial sample size on treatment effect estimates: meta-epidemiological study. BMJ 2013;346:f2304. [DOI: 10.1136/bmj.f2304]

Dechartres 2014

Dechartres A, Altman DG, Trinquart L, Boutron I, Ravaud P. Association between analytic strategy and estimates of treatment outcomes in meta-analyses. JAMA 2014;312(6):623-30. [DOI: 10.1001/jama.2014.8166]

Deeks 2017

Deeks JJ, Higgins JP, Altman DG (editors) on behalf of the Cochrane Statistical Methods Group. Chapter 9: Analysing data and undertaking meta-analyses. In: Higgins JPT, Churchill R, Chandler J, Cumpston MS (editors), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017), Cochrane, 2017. Available from www.training.cochrane.org/handbook.

Eikermann 2012

Eikermann M, Grosse-Sundrup M, Zaremba S, Henry ME, Bittner EA, Hoffmann U, et al. Ketamine activates breathing and abolishes the coupling between loss of consciousness and upper airway dilator muscle dysfunction. Anesthesiology 2012;116(1):35-46. [DOI: 10.1097/ALN.0b013e31823d010a]

Elia 2005

Elia N, Tramer M. Ketamine and postoperative pain – a quantitative systematic review of randomised trials. Pain 2005;113:61-70. [DOI: 10.1016/j.pain.2004.09.036]

Farrar 2000

Farrar JT, Portenoy RK, Berlin JA, Kinman JL, Strom BL. Defining the clinically important difference in pain outcome measures. Pain 2000;88(3):987-94.

Fisher 2000

Fisher K, Coderre T, Hagen NA. Targeting the N-methyl-D-aspartate receptor for chronic pain management: preclinical animal studies, recent clinical experience and future research directions. Journal of Pain and Symptom Management 2000;20(5):358-73. [DOI: 10.1016/S0885-3924(00)00213-X]

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Flather MD, Farkouh ME, Pogue JM, Yusuf S. Strengths and limitations of meta-analysis: larger studies may be more reliable. Controlled Cinical Trials 1997;18(6):568-79. [DOI: 10.1016/S0197-2456(97)00024-X]

Gavaghan 2000

Gavaghan DJ, Moore RA, McQuay HJ. An evaluation of homogeneity tests in meta-analyses in pain using simulations of individual patient data. Pain 2000;85(3):415-24. [DOI: 10.1016/S0304-3959(99)00302-4]

Geisslinger 1993

Geisslinger G, Hering W, Thomann P, Knoll R, Kamp HD, Brune K. Pharmacokinetics and pharmaco-dynamics of ketamine enantiomers in surgical patients using a stereoselective analytical method. British Journal of Anesthesia 1993;70(6):666-71. [DOI: 10.1093/bja/70.6.666]

GRADE 2004

GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ 2004;328:1490-4.

Guyatt 2011

Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M et al. GRADE guidelines: 7. Rating the quality of evidence--inconsistency. Journal of Cinical Epidemiology 2011;64(12):1294-302. [DOI: 10.1016/j.jclinepi.2011.03.017]

Guyatt 2013a

Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso-Coello P et al. GRADE guidelines: 11. Making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. Journal of Clinical Epidemiology 2013;66:151-7. [DOI: 10.1016/j.jclinepi.2012.01.006]

Guyatt 2013b

Guyatt GH, Oxman AD, Santesso N, Helfand M, Vist G, Kunz R, et al. GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes. Journal of Clinical Epidemiology 2013;66:158-72. [DOI: 10.1016/j.jclinepi.2012.01.012]

Hayashi 2011

Hayashi Y, Kawaji K, Sun L, Zhang X, Kogano K, Yokoyama T, et al. Microglial Ca-activated K-channels are possible molecular targets for the analgesic effects of s-ketamine on neuropathic pain. Journal of Neuroscience 2011;31(48):17,370-82. [DOI: 10.1523/JNEUROSCI.4152-11.2011]

Heesen 2014

Heesen M, Böhmer J, Brinck EC, Kontinen VK, Klöhr S, Rossaint R, et al. Intravenous ketamine during spinal and general anaesthesia for caesarean section: systematic review and meta-analysis. Acta Anaesthesiologica Scandinavica 2015;59(4):414-26. [DOI: 10.1111/aas.12468]

Higgins 2003

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ 2003;327:557-60.

Higgins 2011a

Higgins JP, Deeks JJ (editors). Chapter 7: Selecting studies and collecting data. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.

Higgins 2011b

Higgins JP, Deeks JJ, Altman DG (editors). Chapter 16: Special topics in statistics. In: Higgins JPT, Green S (editors), Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.

Higgins 2017

Higgins JP, Altman DG, Sterne JA (editors). Chapter 8: Assessing risk of bias in included studies. In: Higgins JPT, Churchill R, Chandler J, Cumpston MS (editors), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017), Cochrane, 2017. Available from www.training.cochrane.org/handbook.

Hirota 2011

Hirota K, Lambert DG. Ketamine: new uses for an old drug? British Journal of Anaesthesia 2011;107(2):123-6. [DOI: 10.1093/bja/aer221]

IntHout 2015

IntHout J, Ioannidis JP, Borm GF, Goeman JJ. Small studies are more heterogeneous than large ones: a meta-meta-analysis. Journal of Clinical Epidemiology 2015;68:860-9. [DOI: 10.1016/j.jclinepi.2015.03.017]

Jevtović‐Todorović 1998

Jevtović-Todorović V, Todorović SM, Mennerick S, Powell S, Dikranian K, Benshoff N, et al. Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin. Nature Medicine 1998;4(4):460-3. [DOI: 10.1038/nm0498-460]

Jevtovic‐Todorovic 2000

Jevtovic-Todorovic V, Benshoff N, Olney JW. Ketamine potentiates cerebrocortical damage induced by the common anaesthetic agent nitrous oxide in adult rats. British Journal of Pharmacology 2000;130(7):1692-8. [DOI: 10.1038/sj.bjp.0703479]

Katz 2009

Katz J, Seltzer Z. Transition from acute to chronic postsurgical pain: risk factors and protective factors. Expert Review of Neurotherapeutics 2009;9(5):723-44. [DOI: 10.1586/ern.09.20]

Kay 1971

Kay B. A clinical investigation of piritramide in the treatment of postoperative pain. British Journal of Anaesthesia 1971;43:1167-71. [DOI: 10.1093/bja/43.12.1167]

Kehlet 2006

Kehlet H, Jensen TJ, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet 2006;367:1618-25.

Kulinskaya 2015

Kulinskaya E, Dollinger MB. An accurate test for homogeneity of odds ratios based on Cochran's Q-statistic. BMC Medical Research Methodology 2015;15:49. [DOI: 10.1186/s12874-015-0034-x]

Kumar 1999

Kumar N, Rowbotham DJ. Editorial II. Piritramide. British Journal of Anaesthesia 1999;82(1):3-5.

Laskowski 2011

Laskowski K, Stirling A, McKay WP, Hyun JL. A systematic review of intravenous ketamine for postoperative analgesia. Canadian Journal of Anaesthesia 2011;58:911-23.

Lee 2011

Lee M, Silverman S, Hansen H, Patel V, Manchikanti L. A comprehensive review of opioid-induced hyperalgesia. Pain Physician 2011;14:145-61.

Lefebvre 2011

Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 (updated March 2011). The Cochrane Collaboration, 2011. Available from www.handbook.cochrane.org.

Lilius 2015

Lilius TO, Jokinen V, Neuvonen MS, Niemi M, Kalso EA, Rauhala PV. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat. British Journal of Pharmacology 2015;172(11):2799-813.

Low 2012

Low Y, Clarke CF, Huh BK. Opioid-induced hyperalgesia: a review of epidemiology, mechanisms and management. Singapore Medical Journal 2012;53(5):537-60.

Lundeberg 2012

Lundeberg S. Pharmacokinetic and pharmacodynamic aspects on opioid administration, morphine and ketobemidone, in the pediatric population [Doctoral thesis]. Stockholm, Sweden: Department of Physiology and Pharmacology, Section of Anesthesiology and Intensive Care, Karolinska Institutet, 2012.

Macintyre 2010

Macintyre PE, Schug SA, Scott DA, Visser EJ, Walker SM, APM:SE Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine. Acute Pain Management: Scientific Evidence. 3rd edition. Melbourne ANZCA & FPM, 2010. [ONLINE ISBN: 978-0-9775174-5-9]

Mao 2002

Mao J. Opioid-induced abnormal pain sensitivity: implications in clinical opioid therapy. Pain 2002;100:213-7.

Marland 2013

Marland S, Ellerton J, Andolfatto G, Strapazzon G, Thomassen O, Brandner B, et al. Ketamine: use in anesthesia. CNS Neuroscience and Therapeutics 2013;19:381-9. [DOI: 10.1111/cns.12072]

McQuay 2012

McQuay HJ, Derry S, Eccleston C, Wiffen PJ, Moore RA. Evidence for analgesic effect in acute pain - 50 years on. Pain 2012;153(7):1364-7. [DOI: 10.1016/j.pain.2012.01.024]

Mhuircheartaigh 2009

Mhuircheartaigh RJ, Moore RA, McQuay HJ. Analysis of individual patient data from clinical trials: epidural morphine for postoperative pain. British Journal of Anaesthesia 2009;103(6):974-81. [DOI: 10.1093/bja/aep300]

Mion 2013

Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neuroscience & Therapeutics 2013;19:370-80. [DOI: 10.1111/cns.12099]

Moher 2009

Moher D, Liberati A, Tetzlaff J, Altman DG, the PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Medicine 2009;6(7):e1000097.

Moore 1998

Moore RA, Gavaghan D, Tramer MR, Collins SL, McQuay HJ. Size is everything -large amounts of information are needed to overcome random effects in estimating direction and magnitude of treatment effects. Pain 1998;78:209-16. [DOI: 10.1016/S0304-3959(98)00140-7]

Moore 2008

Moore RA. Systematic reviews: Are we getting it right yet? In: Moore RA, Kalso E, McQuay HJ, editors(s). Systematic Reviews in Pain Research: Methodology Refined. 1 edition. Seattle: IASP Press, 2008:3-14.

Moore 2010

Moore RA, Moore OA, Derry S, Peloso PM, Gammaitoni AR, Wang H. 10.Responder analysis for pain relief and numbers needed to treat in a meta-analysis of etoricoxib osteoarthritis trials: bridging a gap between clinical trials and clinical practice. Annals of the Rheumatic Diseases 2010;69(2):374-9. [DOI: 10.1136/ard.2009.107805]

Moore 2011

Moore RA, Ní Mhuirchearthaigh RJ, Derry S, McQuay HJ. Mean analgesic consumption is inappropriate for testing analgesic efficacy in post-operative pain: analysis and alternative suggestion. European Journal of Anaesthesiology 2011;28:427-32. [DOI: 10.1097/EJA.0b013e328343c569]

Moore 2013

Moore RA, Straube S, Aldington D. Pain measures and cut-offs - 'no worse than mild pain' as a simple, universal outcome. Anaesthesia 2013;68(4):400-12. [DOI: 10.1111/anae.12148]

Nüesch 2010

Nüesch E, Trelle S, Reichenbach S, Rutjes AW, Tschannen B, Altman DG, et al. Small study effects in meta-analyses of osteoarthritis trials: meta-epidemiological study. BMJ 2010;341:c3515. [DOI: 10.1136/bmj.c3515]

Patanwala 2007

Patanwala AE, Duby J, Waters D, Erstad BL. Opioid conversion in acute care. The Annals of Pharmacotherapy 2007;41:255-67. [DOI: 10.1345/aph.1H421]

Peltoniemi 2016

Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine. A review of clinical pharmacokinetics and pharmacodynamics in anesthesia and pain therapy. Clinical Pharmacokinetics 2016;55:1059-77.

Pereira 2001

Pereira J, Lawlor P, Vigano A, Dorgan M, Bruera E. Equianalgesic dose ratios for opioids: a critical review and proposals for long-term dosing. Journal of Pain and Symptom Management 2001;22(2):672-87. [DOI: 10.1016/S0885-3924(01)00294-9]

Pogue 1997

Pogue JM, Yusuf S. Cumulating evidence from randomized trials: utilizing sequential monitoring boundaries for cumulative meta-analysis. Controlled Clinical Trials 1997;18(6):580-93. [DOI: 10.1016/S0197-2456(97)00051-2]

Pogue 1998

Pogue JM, Yusuf S. Overcoming the limitations of current meta-analysis of randomised controlled trials. Lancet 1998;351(9095):47-52. [DOI: 10.1016/S0140-6736(97)08461-4]

Prabhakar 2014

Prabhakar A, Mancuso KF, Owen CP, Lissauer J, Merritt CK, Urman RD, et al. Perioperative analgesia outcomes and strategies. Best Practice & Research Clinical Anaesthesiology 2014;28:105-15.

Price 2000

Price DD, Mayer DJ, Mao J, Caruso F. NMDA-receptor antagonists and opioid receptor interactions as related to analgesia and tolerance. Journal of Pain and Symptom Management 2000;S1:S7-15. [DOI: 10.1016/S0885-3924(99)00121-9]

Review Manager 2014 [Computer program]

Nordic Cochrane Centre, The Cochrane CollaborationReview Manager 5 (RevMan 5). Version 5.3. Copenhagen: Nordic Cochrane Centre, The Cochrane Collaboration, 2014.

Roberts 2015

Roberts I, Ker K, Edwards P, Beecher D, Manno D, Sydenham E. The knowledge system underpinning healthcare is not fit for purpose and must change. BMJ 2015;250:h2463. [DOI: 10.1136/bmj.h2463]

Ruschweyeh 2011

Ruschweyeh, Wilder-Smith O, Drdla R, Liu X-G, Sandkühler J. Long-term potentiation in spinal nociceptive pathways as a novel target for pain therapy. Molecular Pain 2011;7:20.

Sandkühler 2012

Sandkühler J, Gruber-Schoffnegger D. Hyperalgesia by synaptic long-term potentiation (LTP): an update. Current Opinion in Pharmacology 2012;12(1):18-27. [DOI: 10.1016/j.coph.2011.10.018]

Schmid 1999

Schmid RL, Sandler NA, Katz J. Use and efficacy of low-dose ketamine in the management of acute postoperative pain: a review of current techniques and outcomes. Pain 1999;82(2):111-25. [DOI: 10.1016/S0304-3959(99)00044-5]

Schünemann 2017

Schünemann HJ, Oxman AD, Vist GE, Higgins JP, Deeks JJ, Glasziou P, et al, on behalf of the Cochrane Applicability and Recommendations Methods Group. Chapter 12: Interpreting results and drawing conclusions. In: Higgins JPT, Churchill R, Chandler J, Cumpston MS (editors), Cochrane Handbook for Systematic Reviews of Interventions version 5.2.0 (updated June 2017). Cochrane, 2017. Available from www.training.cochrane.org/handbook.

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Sigtermans M, Dahan A, Mooren R, Bauer M, Kest B, Sarton E, et al. S(+)-ketamine effect on experimental pain and cardiac output a population pharmacokinetic-pharmacodynamic modeling study in healthy volunteers. Anesthesiology 2009;111:892-903. [DOI: 10.1097/ALN.0b013e3181b437b1]

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Silverman JM. Opioid induced hyperalgesia: clinical implications for the pain practitioner. Pain Physician 2009;12:679-84.

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Zhou C, Douglas JE, Kumar NN, Shu S, Bayliss DA, Chen XC. Forebrain HCN1 channels contribute to hypnotic actions of ketamine. Anesthesiology 2013;118(4):785-95. [DOI: 10.1097/ALN.0b013e318287b7c8]

Referencias de otras versiones publicadas de esta revisión

Ir a:

Bell 2006

Bell FR, Dahl JD, Moore RA, Kalso EA. Perioperative ketamine for acute postoperative pain. Cochrane Database of Systematic Reviews 2006, Issue 1. Art. No: CD004603. [DOI: 10.1002/14651858.CD004603.pub2]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Abdolahi 2013

Study characteristics

Methods

Randomised, placebo control

Participants

N = 88, about 41% women

Interventions

Ketamine 0.5 mg/kg bolus IV during induction of anaesthesia

Outcomes

Pain intensity (VAS). Analgesic consumption. Pain outcomes reported during the recovery room stay. PONV

Surgery type

Ophthalmic surgery (retinal detachment, strabismus, keratoplasty)

Group numbers after end of study (treatment/control)

44/44

Age of patient population (treatment/control)

35 ± 13.4

36.3 ± 17.8

Notes

No funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not described

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded investigator not participating in patient care performed data collection

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

44 participants per treatment arm
Adam 2005

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, about 68% women

Interventions

Ketamine 0.5 mg/kg bolus IV just after the induction of anaesthesia followed by a continuous infusion of 3 µg/kg/min intraoperatively and then 1.5 µg/kg/min for 48 h postoperatively

Outcomes

Pain intensity (VAS) before and after mobilisation. PCA morphine consumption. Main outcomes reported hourly for 4 h, then every 4 h for 48 h. Time to first analgesic request. AEs

Surgery type

Total knee arthroplasty

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

68 ± 8

69 ± 6

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A random number table was generated

Allocation concealment (selection bias)

Low risk

Allocation concealed in sealed and sequentially numbered envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel; a nurse not involved in the evaluation of the participants prepared study drugs

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel; none of the other investigators involved in participant management and data collection was aware of the group assignment.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

5% was withdrawn

Selective reporting (reporting bias)

High risk

No data available of all predefined AEs

Size

High risk

20 participants per treatment arm
Adriaenssens 1999

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 30, about 77% women

Interventions

Ketamine IV infusion initially 10 µg/kg/min, gradually decreased to 2.5 µg/kg/min for 48 h after surgery

Outcomes

Pain intensity (VAS). PCA morphine consumption. AEs. Outcomes reported at 0, 1, 2, 4, 6, 12, 24, 36 and 48 h after surgery

Surgery type

Laparotomy

Group numbers after end of study (treatment/control)

15/15

Age of patient population (treatment/control)

Mean values (range)

53 (27‐83)

51 (17‐82)

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described, only mentioned "patients were randomly allocated"

Allocation concealment (selection bias)

Unclear risk

Allocation concealment not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Said to be double‐blind but blinding process not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

All pre‐defined outcomes reported

Size

High risk

15 participants per treatment arm
Aida 2000

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 121, of whom 60 participants in groups 2 and 4 (IV ketamine and control). 40% women

Interventions

  1. Ketamine 1 mg/kg IV prior to surgical incision, 0.5 mg/kg/h infusion IV until skin closure

  2. Morphine ED bolus prior to surgical incision + infusion + placebo IV bolus + continuous infusion until skin closure

  3. Placebo ED + ketamine IV bolus 1 mg/kg + infusion 0.5 mg/kg/h

  4. Morphine ED + ketamine IV

Outcomes

Pain intensity (VAS). Maximum 48 h pain (categorical scale). PCA morphine consumption. Outcomes reported at 6, 12, 24 and 48 h

Surgery type

Distal or total gastrectomy

Group numbers after end of study (treatment/control)

29/31

Age of patient population (treatment/control)

62 ± 14

63 ± 13

Notes

Support from institutional and/or departmental sources

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "According to a computer‐generated table of random number assignments, each patient was assigned to one of four groups."

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "The study supervisor prepared the drug solutions, which were sealed in an envelope and transferred to the anesthesiologist blinded to the solutions."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes were reported

Size

High risk

29 and 31 participants per treatment arms, respectively
Aqil 2011

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 120, about 58% women

Interventions

  1. Ketamine 0.5 mg/kg bolus IV at induction

  2. Ketamine 1 mg/kg bolus IV

  3. Ketamine 1.5 mg/kg bolus IV

Outcomes

Pain intensity (VAS). Pain intensity results not reported though predefined in methods. Analgesic consumption (ketoprofen) at 24 h. AEs

Surgery type

Septorhinoplasty

Group numbers after end of study (treatment/control)

90/30

Age of patient population (treatment/control)

22.9 ± 4.5

22.3 ± 3.89

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel and identical study drug syringes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

High risk

VAS scores not reported but defined in methods. Time to first request for analgesia reported but not predefined

Size

High risk

30 participants per treatment arm
Argiriadou 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 45, 20% women

Interventions

  1. S‐ketamine 0.5 mg/kg bolus IV prior to surgical incision

  2. Pre‐incisional S‐ketamine 0.5 mg/kg bolus IV + intraoperative 0.2 mg/kg boluses IV at 20‐min intervals until skin closure

Outcomes

Pain intensity (VAS). Cumulative consumption of diclofenac and dextropropoxyphene. Outcomes recorded at 3, 6 and 24 h after awakening.

Surgery type

Major abdominal surgery

Group numbers after end of study (treatment/control)

30/15

Age of patient population (treatment/control)

61 ± 14

61 ± 10

Notes

Supported in part by Pfizer Parke‐Davis Pharmaceuticals, Freiburg‐ Karlsruhe, Germany.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation table.

Quote: "With use of a computer‐generated randomization table, patients were assigned to one of three groups."

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "Patients and personnel who participated in the study were unaware of group assignment."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "Patients and personnel who participated in the study were unaware of group assignment."

Incomplete outcome data (attrition bias)
All outcomes

High risk

11% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported adequately

Size

High risk

30 and 15 participants per treatment arm
Argiriadou 2011

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 80, 21% women

Interventions

Pre‐incisional S‐ketamine 0.5 mg/kg bolus IV + intraoperative infusion 6.7µg/kg/min until 20 min before the end of surgery

Outcomes

Pain intensity (VAS) at 4, 12, 24 and 48 h after surgery at rest and during movement (coughing). Supplemental analgesic requirement. Pulmonary function. Return of bowel functions. Length of ICU and hospital stay

Surgery type

Elective open thoracotomy

Group numbers after end of study (treatment/control)

27/26

Age of patient population (treatment/control)

52 ± 17

59 ± 11

Notes

No funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation schedule

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2% was withdrawn

Selective reporting (reporting bias)

Low risk

All predefined outcomes reported

Size

High risk

26, 27 and 27 participants per treatment arm
Arikan 2016

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 120, of whom 80 participants in IV ketamine and control treatment arms. 100% women

Interventions

Postoperatively:

  1. ketamine 0.2 mg/kg IV bolus followed by an infusion of ketamine 0.05 mg/kg/h for 48 h

  2. 0.9% saline bolus IV followed by an infusion of 0.9% saline for 48 h

  3. (IV bolus of magnesium 50 mg/kg followed by an infusion of magnesium 10 mg/kg/h)

Outcomes

48 h cumulative morphine consumption. Pain intensity (NPRS) reported at 2, 6, 12, 24 and 48 h postoperatively. AEs

Surgery type

Total abdominal hysterectomy

Group numbers after end of study (treatment/control)

40/40

Age of patient population (treatment/control)

59.35 ± 4.96

58.46 ± 5.71

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation list

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

40 participants per treatment arm
Ataskhoyi 2013

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, 100% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV

Outcomes

Pain intensity (VAS) reported at 1, 2, 3, 6, 12 and 24 h postoperatively. Time to first request for analgesia. Analgesic consumption reported at 24 h. AEs

Surgery type

Diagnostic gynaecological laparoscopy

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

32.7 ± 3.4

34.3 ± 5.4

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded outcome assessors

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

30 participants per treatment arm
Aubrun 2008

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 90, 100% women

Interventions

Pre‐incisional ketamine 0.15 mg/kg bolus IV + IV PCA ketamine 0.5 mg/bolus

Outcomes

Pain intensity (VAS). Analgesic consumption. AEs. Outcomes reported every 6 h up to 48 h

Surgery type

Major gynaecological operation

Group numbers after end of study (treatment/control)

45/45

Age of patient population (treatment/control)

50 ± 10

49 ± 12

Notes

Support provided by departmental sources

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

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

12% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

45 participants per treatment arm
Aveline 2006

Study characteristics

Methods

Randomised, double‐blind, ketamine vs ketamine + morphine vs morphine

Participants

N = 69, of whom 45 participants in IV ketamine and control arms. About 50% women

Interventions

Pre‐incisional bolus of ketamine 0.15 mg/kg + morphine 0.1 mg/kg IV

Outcomes

Pain intensity (VAS). Analgesic consumption. AEs. Outcomes reported every 4 h up to 24 h

Surgery type

Elective surgical lumbar discectomy with partial laminectomy and nucleotomy

Group numbers after end of study (treatment/control)

45/23

Age of patient population (treatment/control)

46.6 ± 10.6

44.4 ± 11.2

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated list of random numbers

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

22, 23 and 23 participants per treatment arm
Aveline 2009

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 75, of whom 49 participants in IV ketamine and control arms. About 61% women

Interventions

Pre‐incisional ketamine 0.2 mg/kg bolus IV + continuous IV infusion 120 µg/kg/h until the end of surgery, then 60 µg/kg/h until the second postoperative day

Outcomes

Pain intensity (VAS). Analgesic consumption. Time to first morphine demand, AEs. Pain outcomes reported at 2, 6, 12 24 and 48 h

Surgery type

Elective unilateral total knee replacement

Group numbers after end of study (treatment/control)

25/24

Age of patient population (treatment/control)

71 ± 9

70 ± 7

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated list of random numbers

Allocation concealment (selection bias)

Low risk

Sequence allocation concealed by opaque, sealed envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

4% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

25, 24 and 25 participants per treatment arm
Ayoglu 2005

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, of whom 40 participants in IV ketamine and control treatment arms. 65% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV + infusion 0.15 mg/kg/h for the next 4 h

Outcomes

Pain intensity (VRS, NRS). PCA morphine requirement. Pain outcomes reported hourly up to 4 h postoperatively, then at 8 and 20 h postoperatively. AEs

Surgery type

Laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

52.9 ± 9

49.1 ± 3.7

Notes

Third group received a bolus and infusion of magnesium sulphate. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation done by using coloured balls

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

High risk

Unpleasant dreams not predefined in 'methods' but reported in 'results'

Size

High risk

20 participants per treatment arm. Lacks power analysis
Barreveld 2013

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 59, 56% women

Interventions

Postoperative ketamine 0.2 mg/kg/h infusion IV for 24 h

Outcomes

Pain intensity (NRS for categorical pain states). Analgesic consumption at 24 h. AEs

Surgery type

Nononcologic surgery leading to hospitalisation

Group numbers after end of study (treatment/control)

29/30

Age of patient population (treatment/control)

48.5 ± 11.9

55 ± 11.2

Notes

Intraoperative anaesthetic management was at the discretion of the attending anaesthetist (not standardised). No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described in detail

Allocation concealment (selection bias)

Low risk

Central allocation by Investigational Drug Service (IDS (a third party)). IDS also prepared study solutions that were identical in appearance and labelled as "ketamine/placebo"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel assessed outcomes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

8% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

29 and 30 participants per treatment arm
Bilgen 2012

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 140, 100% women

Interventions

Before induction of anaesthesia

  1. Ketamine 0.25 mg/kg

  2. Ketamine 0.5 mg/kg

  3. Ketamine 1 mg/kg bolus IV

Outcomes

Pain intensity (NRS). Analgesic consumption. Outcomes reported at 2, 6, 12, 18, 24, 48 h and 2 weeks, 1 and 6 months and 1 year postoperatively

Surgery type

Caesarean section

Group numbers after end of study (treatment/control)

105/35

Age of patient population (treatment/control)

31 ± 4

32 ± 4

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Unclear risk

Allocation method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

High risk

Outcomes that are not defined in "methods" are reported

Size

High risk

35 participants per treatment arm
Bornemann‐Cimenti 2016

Study characteristics

Methods

Randomised, triple‐blind, placebo control

Participants

N = 60, about 52% women

Interventions

After induction of anaesthesia

  1. 0.25 mg/kg IV bolus of S‐ketamine followed by a 0.125 mg/kg/h infusion for 48 h

  2. 0.9% IV saline bolus followed by a 0.015 mg/kg/h infusion of S‐ketamine for 48 h

  3. 0.9% saline bolus IV followed by a 0.9% saline infusion for 48 h

Outcomes

Postoperative opioid consumption, pain intensity (NRS), hyperalgesia at the incision site, delirium scores. Pain outcomes reported over time every 4 h up to 48 h. Hyperalgesia and ICDSC reported at 48 h

Surgery type

Major abdominal surgery

Group numbers after end of study (treatment/control)

37/19

Age of patient population (treatment/control)

60.2 ± 9

61 ± 12.4

Notes

Institutional funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation list

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail. Only mentioned that an anaesthetist with no further involvement in the study prepared and labelled study drug syringes with "study medication" and the randomisation number of the participant

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

An independent anaesthesiologist prepared study drugs. Participants and nursing staff were blinded

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel made outcome assessment

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Burstal 2001

Study characteristics

Methods

Randomised, double‐blind. Ketamine + morphine vs morphine

Participants

N = 70, 100% women

Interventions

Postoperative PCA ketamine 2 mg/bolus IV

Outcomes

Pain intensity (VAS) and PCA morphine consumption reported at 24 and 48 h. Area of allodynia (von Frey) reported at 48 h

Surgery type

Total abdominal hysterectomy

Group numbers after end of study (treatment/control)

37/33

Allodynia subset: 25/18

Age of patient population (treatment/control)

Median values, IQR

43 (10)

45 (7)

Allodynia subset: 45 (10), 44 (7)

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated groups

Allocation concealment (selection bias)

Low risk

Quote: "A sealed envelope system"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

16% was withdrawn

Selective reporting (reporting bias)

Unclear risk

Predefined outcomes reported but surgeon or participant decided on PCA cessation based on how they felt

Size

High risk

37 and 33 participants per treatment arm
Cenzig 2014

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N= 60, about 73% women

Interventions

Intraoperative ketamine infusion 6 µg/kg/min after orotracheal intubation until wound closure

Outcomes

Pain intensity (VAS) and analgesic consumption, reported at 1, 3, 6, 12 and 24 h. Time to first analgesic request. AEs during the first 24 h

Surgery type

Total knee replacement surgery

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

58.2 ± 9.58

58.8 ± 11.5

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Nurses unaware of the study protocol performed assessments

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported adequately

Size

High risk

30 participants per treatment arm
Chazan 2010

Study characteristics

Methods

Randomised, double‐blind

Participants

N = 46, about 35% women

Interventions

Postoperative ketamine 5 mg + morphine 1 mg/bolus IV via PCA vs morphine alone

Outcomes

Pain intensity (VAS) reported at 24 and 48 h. Analgesic consumption reported at 72 h. AEs.

Surgery type

Minimally invasive direct coronary artery bypass, off‐pump coronary artery bypass, thoracotomy

Group numbers after end of study (treatment/control)

24/22

Age of patient population (treatment/control)

60 ± 16

57 ± 18

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation sequence

Allocation concealment (selection bias)

Low risk

Quote: "The allocation sequence of the patients was generated and concealed at the computer"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel and participants

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

22 and 24 participants per treatment arm
Chen 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40. Demographic data of study participants not presented

Interventions

Pre‐incisional ketamine 0.3 mg/kg bolus IV followed by an infusion 3 µg/kg/min until 15 mins prior to completion of the operation

Outcomes

Pain intensity (VAS). Analgesic consumption. Pain outcomes reported at 3, 6, 12, 24 and 48 h postoperatively. Psychotomimetic AEs

Surgery type

Upper abdominal surgery

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

Not mentioned

Notes

Article in Chinese. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Only mentioned "randomised"

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Withdrawals not reported

Selective reporting (reporting bias)

High risk

Not all predefined outcomes reported

Size

High risk

20 participants per treatment arm
Choi 2015

Study characteristics

Methods

Randomised, double‐blind

Participants

N = 75, 100% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV followed by an infusion 5 µg/kg/min

Outcomes

Analgesic consumption reported at 48 h postoperatively. Pain intensity (NRS) reported at 0, 1, 6 and 24 h postoperatively. Time to first analgesic demand. Hyperalgesia (sensory threshold)

Surgery type

Laparoscopic gynaecologic surgery

Group numbers after end of study (treatment/control)

25/25

Age of patient population (treatment/control)

44.4 ± 9.2

43.7 ± 7.6

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Only mentioned "randomised"

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not described

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded investigator

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

25 participants per treatment arm
Colombani 2008

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 208, 100% women

Interventions

Pre‐incisional ketamine 0.15 mg/kg bolus IV followed by an infusion 2 µg/kg/min until the end of surgery

Outcomes

Analgesic consumption reported at 48 h postoperatively. Pain intensity (VAS), reported as participant proportion with VAS score > 4

Surgery type

Breast surgery (partial resection of breast with axillary lymph node evacuation or mastectomy with or without axillary lymph node evacuation)

Group numbers after end of study (treatment/control)

106/102

Age of patient population (treatment/control)

57.6 ± 12.5

59 ± 11.4

Notes

Article in French. Only participant proportion (%) with VAS score > 4 reported. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation list generated at the department of biostatistics

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded participants and personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

5% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

Unclear risk

106 and 102 participants per treatment arm
Crousier 2008

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 36, 100% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV followed by an infusion 0.25 mg/kg/h until wound closure

Outcomes

Pain intensity (VAS) and analgesic consumption reported at 24 h. AEs. Hyperalgesia on 5th postoperative day and after 3 months

Surgery type

Mastectomy

Group numbers after end of study (treatment/control)

18/18

Age of patient population (treatment/control)

60 ± 11

49 ± 12

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Only mentioned double‐blind

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Only mentioned double‐blind

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3% was withdrawn

Selective reporting (reporting bias)

High risk

Pain score measures at certain time points predefined in methods but only average pain scores in the postoperative period reported

Size

High risk

18 participants per treatment arm
D'Alonzo 2011

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, about 43% women

Interventions

Ketamine 0.5 mg/kg bolus IV prior to chest wall incision

Outcomes

Pain intensity (NRS). Reported at baseline, 4 and 24 h postoperatively

Surgery type

Video assisted thoracoscopic surgery or thoracotomy

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

61 ± 12

66 ± 10

Notes

Inflammatory response as a primary outcome of the study. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation list

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Unclear risk

Predefined outcomes reported but the anaesthetic procedure was left to the discretion of the anaesthesiologist; general anaesthesia was supplemented by an epidural catheter placement as needed to control pain (16 participants in the treatment group, 19 participants in the control group)

Size

High risk

20 participants per treatment arm
Dahi‐Taleghani 2014

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 140, 100% men

Interventions

Postoperative ketamine 2 mg + morphine 2 mg via PCA

Outcomes

Pain intensity (VAS) reported at 1, 6 and 24 h postoperatively. Analgesic consumption reported at 24 h postoperatively. AEs

Surgery type

Elective orthopedic surgery for the lower limb

Group numbers after end of study (treatment/control)

70/70

Age of patient population (treatment/control)

39.1 ± 7.2

38.3 ± 7.5

Notes

The study was supported financially in part by a research grant from the Anesthesiology Research Center, Shadid Beheshti University of Medical Sciences, Tehran, Iran

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Only mentioned double‐blind

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Only mentioned double‐blind

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

All predefined outcomes reported

Size

Unclear risk

70 participants per treatment arm
Dahl 2000

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 89, 100% women

Interventions

  1. Ketamine bolus 0.4 mg/kg IV prior to skin incision

  2. Ketamine bolus 0.4 mg/kg IV at skin closure

Outcomes

Pain intensity (VAS, VRS) reported every 1 h up to 6 h postoperatively, then 6‐24 and 24‐96 h. Analgesic consumption at 0‐6, 6‐24 and 24‐48 h postoperatively. Level of activity. AEs

Surgery type

Abdominal hysterectomy

Group numbers after end of study (treatment/control)

60/29

Age of patient population (treatment/control)

50.1 ± 5.3

48 ± 7

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated table of random numbers

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding process not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding process not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

10% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

33 and 27 participants per treatment arm and 29 participants in the control group
Dal 2005

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 90, of whom 60 participants in IV ketamine and control treatment arms. 78% women

Interventions

Ketamine 0.5 mg/kg bolus IV 20 mins before the end of surgery

Outcomes

Postoperative shivering. Pain intensity (VAS) reported on arrival in the recovery room and at 1st and 2nd h postoperatively. Time to first analgesic requirement. AEs

Surgery type

Various procedures. General anaesthesia for an anticipated duration of 60‐180 mins excluding procedures that might require administration of blood or blood products and urological endoscopic operations

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

45 (21‐66)

43 (18‐65)

Notes

Main outcome was postoperative shivering. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported adequately

Size

High risk

30 participants per treatment arm
Dar 2012

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 90, of whom 60 participants in IV ketamine and control treatment arms. 30% women

Interventions

Ketamine 0.5 mg/kg bolus IV 20 mins before the end of surgery. Various surgical procedures

Outcomes

Postoperative shivering, pain intensity (VAS), AEs, vital parameters. Pain intensity not reported

Surgery type

Various procedures under general anaesthesia with an anticipated duration of 60‐180 mins excluding urological endoscopic operations

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

36.63 ± 1.2

38.7 ± 1.7

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described in detail

Allocation concealment (selection bias)

Low risk

Quote: "Study drugs were prepared, diluted to a volume of 5 ml and presented as coded syringes by an anaesthetist who was not involved in the management of the patients"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

A blinded anaesthetist made assessments

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

High risk

Predefined VAS scores are not reported. Mean time to rescue analgesia is reported even though not predefined in methods.

Size

High risk

30 participants per treatment arm
De Kock 2001

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 100, of whom 60 participants in IV ketamine or control treatment arms. About 48% women

Interventions

  1. ± 30 min before skin incision: ketamine bolus 0.25 mg/kg IV + infusion 0.125 mg/kg/h until end of surgery

  2. ± 30 min before skin incision: ketamine bolus 0.5 mg/kg IV + infusion 0.25 mg/kg/h IV until skin closure

  3. Ketamine 0.25 mg/kg bolus ED + infusion 0.125 mg/kg/h ED until end of surgery

  4. Ketamine 0.5 mg/kg bolus ED + infusion 0.25 mg/kg/h ED until end of surgery

Outcomes

Pain intensity (VAS) reported at 15 min, 2, 6, 12, 24, 36 and 48 h postoperatively. Area of hyperalgesia reported at 24, 48 and 72 h postoperatively. Postoperative residual pain at 2 weeks, 1 and 6 months, 1 year. Cumulative number of met and unmet PCA morphine demands. AEs

Surgery type

Rectal adenocarcinoma surgery

Group numbers after end of study (treatment/control)

40/20

Age of patient population (treatment/control)

67 ± 8.4

67 ± 9

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated table of random numbers

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals in the immediate postoperative period. 8% of participants died during the one‐year follow up

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Deng 2009

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 200, about 43% women

Interventions

  1. Pre‐incisional ketamine 0.5 mg/kg bolus IV + 0.1 mg/kg/h infusion IV during surgery and for 24 h postoperatively

  2. Pre‐incisional ketamine 0.5 mg/kg bolus IV + 0.05 mg/kg/h infusion IV during surgery and for 24 h postoperatively

  3. Pre‐incisional ketamine 0.5 mg/kg bolus IV + 0.01 mg/kg/h infusion IV during surgery and for 24 h postoperatively

Outcomes

Pain intensity (VAS) reported at 24 h postoperatively. PCA remifentanil consumption, reported at 0‐12 h, 12‐24 h and 0‐24 h postoperatively. AEs. Participant satisfaction with analgesia

Surgery type

Lower limb fracture operation

Group numbers after end of study (treatment/control)

150/50

Age of patient population (treatment/control)

49.6 ± 5.6

50.1 ± 6.3

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation method not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Withdrawals not reported

Selective reporting (reporting bias)

Low risk

Predefined outcomes addressed

Size

Unclear risk

50 participants per treatment arm
Du 2011

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, 100% women

Interventions

Preinductional ketamine 0.25 mg/kg bolus IV

Outcomes

Pain intensity (VAS) and analgesic consumption reported at 15 min intervals during the first postoperative hour. AEs

Surgery type

Gynaecological laparoscopic surgery

Group numbers after end of study (treatment/control)

20/20. Power analysis calculated based on the primary outcome (serum glucose level)

Age of patient population (treatment/control)

35.4 ± 7.9

39.1 ± 11.5

Notes

Main outcome was endocrine metabolic and inflammatory responses to preoperative low‐dose ketamine. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated table of random numbers

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded outcome assessors

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Dualé 2009

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 86, about 30% women

Interventions

Ketamine 1 mg/kg bolus IV at induction + 1 mg/kg/h infusion IV

Outcomes

Pain intensity (VAS) reported on arrival in the PACU and 1, 2, 4, 8, 12, 16, 24, 62, 40 and 48 h postoperatively. Analgesic consumption reported at 24 and 48 h postoperatively. AEs. NPSI scores reported at 6 weeks and 4 months postoperatively

Surgery type

Thoracotomy

Group numbers after end of study (treatment/control)

42/44

Age of patient population (treatment/control)

61.9 ± 8.3

58.5 ± 8.5

Notes

No financial arrangements that may represent a conflict of interest

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described in detail

Allocation concealment (selection bias)

Low risk

Quote: "An inclusion number was allocated randomly and kept in a sealed envelope."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

5% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported adequately

Size

High risk

42 and 44 participants per treatment arm
Dullenkopf 2009

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 120; about 59% women

Interventions

  1. Pre‐incisional ketamine 0.15 mg/kg bolus IV

  2. Pre‐incisional ketamine 0.5 mg/kg bolus IV

Outcomes

Pain intensity (VAS) at arrival in PACU and at 3 months postoperatively. Analgesic consumption reported at 24 h postoperatively. AEs

Surgery type

General surgical or orthopaedic operation anticipated to last 30 to 90 mins and assumed hospital stay of 48 h

Group numbers after end of study (treatment/control)

77/33

Age of patient population (treatment/control)

52.6 ± 18

52.3 ± 17.9

Notes

Basis for group size unclear (power analysis not presented). No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated block randomisation

Allocation concealment (selection bias)

Low risk

Study solutions prepared and blinded by a hospital pharmacist (a third party). Syringes containing study drugs identical in appearance

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

8% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

36, 41 and 33 participants per treatment arm
Fiorelli 2015

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 75, 27% women

Interventions

Ketamine 1 mg/kg bolus IV before thoracotomy

Outcomes

Pain intensity (VAS) and morphine consumption reported at 6, 12, 24, 36 and 48 h postoperatively. AEs. Inflammatory response

Surgery type

Thoracotomy

Group numbers after end of study (treatment/control)

38/37

Age of patient population (treatment/control)

59.5 ± 15.3

58.6 ± 17.4

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation list

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7% was withdrawn

Selective reporting (reporting bias)

Low risk

All predefined outcomes reported

Size

High risk

38 and 37 participants per treatment arm
Galinski 2007

Study characteristics

Methods

Randomised, double‐blind. Ketamine + dexamethasone vs dexamethasone

Participants

N = 65, about 26% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV

Outcomes

Pain intensity (VAS) and analgesic consumption, reported at 15 and 30 min postoperatively. AEs

Surgery type

Inguinal hernia repair

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

47.55 ± 17.46

49.6 ± 13.36

Notes

Support provided by institutional and/or departmental sources

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described in detail

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not described in detail, said to be double‐blind

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not described

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Withdrawals not reported

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Ganne 2005

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 61, about 7% women

Interventions

Ketamine 0.15 mg/kg bolus IV before induction of anaesthesia + 2 µg/kg/min infusion IV during anaesthesia

Outcomes

Pain intensity (VAS). Analgesic consumption. AEs. Pain outcomes reported every 8 h up to 48 h postoperatively

Surgery type

Ear, throat and nose surgery

Group numbers after end of study (treatment/control)

30/31

Age of patient population (treatment/control)

56.9 ± 9.5

59.3 ± 8.9

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Low risk

Allocation concealment in sealed envelopes. Syringes containing study drugs were identical in appearance.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

30 and 31 participants per treatment arm
Garcia‐Navia 2016

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 33, 100% women

Interventions

Ketamine 0.5 mg/kg bolus IV prior to incision

Outcomes

Opioid consumption during surgery, emergence time, pain intensity (VAS) on admission to PACU and at 2, 4, 8 and 24 h postoperatively. Analgesic consumption at 24 h postoperatively. AEs

Surgery type

Gynecological laparotomy excluding oncologic surgery

Group numbers after end of study (treatment/control)

11/11

Age of patient population (treatment/control)

43.1 ± 7.2

45.2 ± 4.2

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated list of random numbers

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described. Only mentioned that an independent nurse not involved in the study prepared study solutions

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel assessed outcomes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

11 participants per treatment arm
Garg 2016

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 66, about 63% women

Interventions

Postoperative administration of

  1. ketamine bolus 0.25 mg/kg IV followed by a continuous infusion at a rate of 0.25 mg/kg/h for 24 h or

  2. 0.9% saline bolus IV followed by a 0.9% saline infusion (or an IV bolus of dexmedetomidine 0.5µg/kg followed by an infusion at a rate of 0.3 µg/kg/h

Outcomes

Pain intensity (NRS) at 0, 2, 6, 12, 18, 24 and 48 h postoperatively. Pain‐free period. Analgesic consumption at 12, 24 and 48 h postoperatively. AEs

Surgery type

Spine surgery

Group numbers after end of study (treatment/control)

22/22

Age of patient population (treatment/control)

36.45 ± 13.39

36.32 ± 14.32

Notes

Surgery types include laminectomy and excision, pedicle screw fixation, decompression and stabilisation, detethering and excision of tumour). No funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated randomisation list

Allocation concealment (selection bias)

Low risk

Allocation concealment achieved by sequentially numbered, opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not described in detail. Only mentioned "double‐blind"

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not described in detail. Only mentioned double‐blind

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

22 participants per treatment arm
Gilabert Morell 2002

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 69, 100% women

Interventions

  1. Ketamine 0.15 mg/kg bolus IV at induction

  2. Ketamine 0.15 mg/kg bolus IV at wound closure

Outcomes

Pain intensity (VAS) at rest at 1, 6, 24 and 48 h postoperatively and during movement on 1st and 5th day postoperatively. Time to first request of PCA. Morphine consumption at 6, 24 and 48 h postoperatively. AEs

Surgery type

Hystectomy and adenectomy

Group numbers after end of study (treatment/control)

44/22

Age of patient population (treatment/control)

47.8 ± 8.3

48 ± 7

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

4% was withdrawn

Selective reporting (reporting bias)

Low risk

All predefined outcomes reported

Size

High risk

23 participants per treatment arm
Grady 2012

Study characteristics

Methods

Randomised, double‐blind, placebo control. Factorial design. No direct comparison between ketamine vs non‐ketamine

Participants

N = 64, 100% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV + a continuous infusion 0.12 mg/kg/h until 15 mins before completion of the operation

Outcomes

Pain intensity (VRS) reported on PACU admit and discharge and on 1st and 2nd postoperative days. Analgesic consumption reported in PACU and on 1st and 2nd postoperative days. AEs

Surgery type

Abdominal hysterectomy

Group numbers after end of study (treatment/control)

30/32

Age of patient population (treatment/control)

46 ± 8

46 ± 8

Notes

Internal funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation based on a computer‐generated list

Allocation concealment (selection bias)

Low risk

Allocation maintained in sequentially numbered, sealed, opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

30 and 32 participants per treatment arm.
Guignard 2002

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 50, 50% women

Interventions

Ketamine bolus 0.15 mg/kg + infusion 2 µg/kg/min IV from prior to skin incision until skin closure

Outcomes

Pain intensity (VAS and 4‐point VRS; data not shown). Total morphine consumption (PCA and nurse‐administered) at 0‐4, 5‐24 and 0‐24 h postoperatively. Time to first request for morphine. AEs

Surgery type

Abdominal surgery

Group numbers after end of study (treatment/control)

25/25

Age of patient population (treatment/control)

64 ± 10

61 ± 13

Notes

Supported, in part, by NIH Grant GM 58273 (Bethesda, MD), the Joseph Drown Foundation (Los Angeles, CA), and the Commonwealth of Kentucky Research Challenge Trust Fund (Louisville, KY).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random‐number table

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail. Only mentioned that a hospital pharmacist prepared study drugs

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded person collecting data

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

25 participants per treatment arm
Guillou 2003

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 101, about 54% women

Interventions

Ketamine 0.5 mg/kg bolus IV after surgery + infusion 2 µg/kg/min for 24 h and 1 µg/kg/min from 24‐48 h

Outcomes

Pain intensity (VAS) at rest and during movement. Cumulative dose of PCA morphine. Outcomes reported every 4 h up to 48 h postoperatively

Surgery type

Major abdominal surgery

Group numbers after end of study (treatment/control)

41/52

Age of patient population (treatment/control)

60 ± 16

60 ± 15

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded observer

Incomplete outcome data (attrition bias)
All outcomes

Low risk

8% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

Unclear risk

41 and 52 participants per treatment arm
Hadi 2010

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 30. Table of demographic data not presented

Interventions

Ketamine 1 µg/kg/min infusion IV until the end of surgery

Outcomes

Pain intensity (visual face‐rating scale), reported as number of participants with different degrees of pain. Time to first request for analgesia. Analgesic consumption reported at 24 h postoperatively. AEs

Surgery type

Lumbar and thoracic spinal fusion surgery

Group numbers after end of study (treatment/control)

15/15

Age of patient population (treatment/control)

Age range

53‐59

49‐58

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not described, only mentioned double‐blind

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Data assessment by blinded pharmacy students

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Withdrawals not reported

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported adequately

Size

High risk

15 participants per treatment arm
Hadi 2013

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 45, about 53% women

Interventions

  1. Ketamine 1 µg/kg/min infusion IV intraoperatively

  2. Ketamine 1 µg/kg/min infusion IV intraoperatively and 24 h after surgery

Outcomes

Pain intensity (VAS). Analgesic consumption. Pain outcomes reported at 6, 12 and 24 h postoperatively. Time to first request for analgesia. AEs

Surgery type

Lumbar microdiscectomy

Group numbers after end of study (treatment/control)

30/15

Age of patient population (treatment/control)

55 ± 2.5

51 ± 2.47

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Pharmacist prepared study solutions

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel collecting data

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Unclear risk

Pain intensity scale reported differs (VAS, NRS)

Size

High risk

15 participants per treatment arm
Haliloglu 2015

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 52, 100% women

Interventions

Ketamine 0.5 mg/kg bolus IV at induction followed by an infusion 10 mcg/kg/min until the end of surgery

Outcomes

Pain intensity (NRS) reported at 15 min, at 2 and 6 h, then every 6 h up to 24 h postoperatively. Analgesic consumption reported at 6‐h intervals up to 24 h postoperatively. Cumulative analgesic consumption reported at 24 h postoperatively. Rescue analgesia. AEs

Surgery type

Elective caesarean section

Group numbers after end of study (treatment/control)

26/26

Age of patient population (treatment/control)

29.1 ± 2.2

29 ± 2.2

Notes

No mention of sponsorship or funding. The study authors report that they have no conflicts of interest

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

26 participants per treatment arm
Hasanein 2011

Study characteristics

Methods

Randomised, blinded, placebo controlled

Participants

N = 60, about 47% women

Interventions

Ketamine 1 µg/kg/min infusion IV during anaesthesia

Outcomes

Pain intensity (VAS), reported at 1 and 2 h postoperatively. Time to first request for analgesia. Analgesic consumption, reported at 24 h postoperatively. AEs

Surgery type

Laparoscopic Roux‐en‐Y‐gastric bypass

Group numbers after end of study (treatment/control)

30/30. Power analysis not provided

Age of patient population (treatment/control)

29 ± 6

27 ± 8

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No data provided

Allocation concealment (selection bias)

High risk

The attending anaesthesiologist was aware of the treatment condition but study participants and personnel in the operating room and recording data were unaware of treatment allocation.

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Participants and investigators recording data in the operating room were blinded to the treatment but the attending anaesthesiologist was aware of the treatment condition

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Investigators recording data were blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

High risk

Predefined outcome (PCA morphine consumption during the first 4 h after surgery) is not reported

Size

High risk

30 participants per treatment arm
Hayes 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 45, about 42% women

Interventions

Pre‐induction ketamine 0.5 mg/kg bolus IV followed by 0.15 mg/kg/h infusion IV for 72 h postoperatively

Outcomes

Incidence of post‐amputation pain (phantom and stump pain, number of participants) on 3rd and 6th postoperative day and 6 months after surgery. Analgesic consumption reported at 24 and 72 h postoperatively, reported as medians. Postoperative central sensitisation on 3rd and 6th day postoperatively. AEs

Surgery type

Above or below knee amputation

Group numbers after end of study (treatment/control)

22/23

Age of patient population (treatment/control)

68.7 ± 12.2

68.9 ± 10.9

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A random‐number generator

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7% was withdrawn in the immediate postoperative period

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Helmy 2015

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, 100% women

Interventions

Ketamine 0.3 mg/kg bolus IV before induction of anaesthesia

Outcomes

Pain intensity (VAS) reported at 2, 6, 12 and 24 h postoperatively. Analgesic consumption reported at 24 h postoperatively. Sedation level. PONV. Time to first analgesic request

Surgery type

Elective caesarean section

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

Median (range)

33 (24‐43)

30 (22‐41)

Notes

The authors declare that there is no conflict of interest

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not sufficiently described

Quote: "using a sealed envelope method, parturients were randomly assigned into 3 groups"

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding not described (only said "double blind")

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

19 and 20 participants per treatment arm
Hercock 1999

Study characteristics

Methods

Randomised, double‐blind. Intraoperative IV ketamine vs placebo/postoperative ketamine vs morphine

Participants

N = 50, 100% women

Interventions

Ketamine 0.3 mg/kg bolus IV after induction. Postoperative IV PCA 1 mg/bolus

Outcomes

Pain intensity. PCA morphine consumption. Outcomes reported at 24 h postoperatively

Surgery type

Total abdominal hysterectomy

Group numbers after end of study (treatment/control)

24/25

Age of patient population (treatment/control)

45.7

45.8

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Low risk

An independent anaesthetist, who subsequently had no role in the care of the participant, prepared the study drugs. Allocation was concealed in sealed, sequentially numbered envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

24 and 25 participants per treatment arm
Hu 2014

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 78, about 19% women

Interventions

Pre‐incisional ketamine 0.1 mg/kg bolus IV followed by an infusion 2 µg/kg/min for 72 h

Outcomes

Pain intensity (NRS) reported on the 1st 7 postoperative days and at 2 and 6 months after surgery. Analgesic consumption reported at 72 h postoperatively. AEs. Evaluation of chronic postoperative pain

Surgery type

Muscle‐sparing axillary thoracotomy

Group numbers after end of study (treatment/control)

31/47

Age of patient population (treatment/control)

51.39 ± 9.85

48.28 ± 13.95

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Only mentioned "double blind"

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Only mentioned "double blind"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

4% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

31 and 47 participants per treatment arm
Ilkjaer 1998

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, about 38% women

Interventions

Ketamine 10 mg bolus IV before surgical incision + 10 mg/h infusion IV for 48 h postoperatively

Outcomes

Pain intensity (VAS) at rest and during movement, reported at 4, 6, 8 h, then beginning at 22nd postoperative h every 2 h up to 32 h postoperatively, then at 46 and 48 h postoperatively. Number of PCA morphine doses at 0‐24 h and 24‐48 h postoperatively. Pressure pain detection threshold at 0, 6, 22, 30 and 46 h postoperatively. Pain sensitivity. AEs

Surgery type

Elective nephrectomy or operation on pelvic structures

Group numbers after end of study (treatment/control)

24/28

Age of patient population (treatment/control)

Median age

50 (43‐68)

55 (50‐65)

Notes

Supported by a grant from the Danish Medical Council (Reg. no. 28809), Novo Nordisk Foundation, Danish Foundation for the Advancement of Medical Science and Agnes and Poul Friis Foundation

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Low risk

Quote: "Study drugs (ketamine 10 mg/ml) and placebo (isotonic saline) were prepared under sterile conditions by the hospital pharmacy in identical containers, marked with the name of the project, the investigator's name and consecutive patient number"

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Only stated "double‐blind" but blinding process not described in detail

Incomplete outcome data (attrition bias)
All outcomes

High risk

13% was withdrawn from the study and completed participants were analysed

Selective reporting (reporting bias)

Unclear risk

Insufficient information (precise numbers) of some outcomes, only reported P values

Size

High risk

24 and 28 participants per treatment arm
Jaksch 2002

Study characteristics

Methods

Randomised, double‐blind, placebo‐control

Participants

N = 30, 50% women

Interventions

S‐ketamine 0.5 mg/kg bolus IV before incision + infusion 2 µg/kg/min until 2 h after emergence from anaesthesia

Outcomes

Pain intensity (VAS) and PCA morphine consumption reported at 1, 24, 48, 72 and 120 h postoperatively. Time to first request for analgesia

Surgery type

Elective arthroscopic anterior cruciate ligament repair

Group numbers after end of study (treatment/control)

15/15

Age of patient population (treatment/control)

30 ± 8

33 ± 7

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not described

Allocation concealment (selection bias)

Low risk

Quote: "Envelopes containing identification of the preparation administered were available for emergencies"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Nurses not involved in the study prepared study solutions

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

15 participants per treatment arm
Javery 1996

Study characteristics

Methods

Randomised, double‐blind. Ketamine + morphine vs morphine

Participants

N = 42, about 10% women

Interventions

Postoperative IV PCA ketamine 1 mg/bolus

Outcomes

Pain intensity (VAS). PCA morphine consumption. AEs. Outcomes reported at 24 h postoperatively

Surgery type

Lumbar microdiscectomy

Group numbers after end of study (treatment/control)

22/20

Age of patient population (treatment/control)

37.3 ± 9.9

39.5 ± 7.2

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 and 22 participants per treatment arm
Jendoubi 2017

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, of whom 40 participants in IV ketamine and control treatment arms. 50% women

Interventions

At the induction of anaesthesia, ketamine bolus 0.15 mg/kg IV followed by infusion of 0.1 mg/kg/h for 24 h postoperatively

Outcomes

Cumulative morphine consumption reported every 6 h up to 24 h postoperatively. Pain intensity (VAS) at rest and during movement and coughing every 6 h up to 24 h and at 48 h postoperatively. AEs

Surgery type

Open nephrectomy

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

55.8 ± 13.5

48.3 ± 13.5

Notes

No sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described in detail. Only stated "randomised"

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail. Only mentioned that a nurse not participating in the study prepared study drugs

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

5% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Joly 2005

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 75, of whom 50 participants in IV ketamine and control treatment arms. 64% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV + 5 µg/kg/min infusion IV until skin closure, then 2 µg/kg/min during the initial 48 postoperative hours

Outcomes

Pain intensity (VAS) reported at 24 and 48 h postoperatively. Analgesic consumption reported at 48 h postoperatively. AEs. Hyperalgesia on day 1 and 2 postoperatively

Surgery type

Major abdominal surgery

Group numbers after end of study (treatment/control)

24/25

Age of patient population (treatment/control)

59 ± 13

56 ± 12

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Low risk

Allocation concealed in sealed, sequentially numbered envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

1% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

25 participants per treatment arm
Joseph 2012

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, about 53% women

Interventions

Ketamine 0.5 mg/kg bolus IV at anaesthesia induction + IV infusion 3 µg/kg/min during surgery, then 1.5 µg/kg/min for 48 h postoperatively

Outcomes

Pain intensity (NRS). Cumulative epidural ropivacaine consumption. Supplemental IV analgesia requirement. AEs. Outcomes reported on admission to PACU, at 12, 24, 48 h and 1 and 3 months after surgery

Surgery type

Thoracotomy

Group numbers after end of study (treatment/control)

22/25

Age of patient population (treatment/control)

median age (range)

60 (24‐80)

60 (31‐79)

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Patients were randomized to one of the two groups using a computer‐generated randomization schedule."

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail. Only described that a hospital pharmacist dispensed study drugs that were identical in appearance

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7% was withdrawn

Selective reporting (reporting bias)

Low risk

Results of predefined outcomes reported

Size

High risk

22 and 25 participants per treatment arm
Kafali 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, about 48% women

Interventions

Pre‐incisional ketamine 0.15 mg/kg bolus IV

Outcomes

Pain intensity (VAS) reported at 30 min, then 2, 12, 24 and 48 h postoperatively. Time to first analgesic demand. Analgesic consumption reported at 48 h postoperatively. Adverse effects

Surgery type

Lower abdominal surgery

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

47.2 ± 4.2

45.2 ± 3

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A random number table

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding not described, mentioned "double blind"

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding not described, only mentioned "double‐blind"

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

High risk

Not all predefined outcomes are reported (adverse effects: pruritus)

Size

High risk

30 participants per treatment arm
Kakinohana 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 50, 58% women

Interventions

Pre‐incisional ketamine bolus 1 mg/kg IV + infusion 1 mg/kg/h IV, maintained until 2 mg/kg administered

Outcomes

Pain intensity (VAS) reported at 5, 24 and 48 h postoperatively. Cumulative PCEA volume consumed reported at 5 h, 5‐24 h, 24‐48 h and at 48 h postoperatively. AEs

Surgery type

Elective open cholecystectomy

Group numbers after end of study (treatment/control)

25/25

Age of patient population (treatment/control)

48.1 ± 10.1

49.9 ± 12.0

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Assessment accomplished by blinded nurses

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

25 participants per treatment arm
Kamal 2008

Study characteristics

Methods

Randomised, double‐blind. Ketamine + morphine vs morphine

Participants

N = 80, about 49% women

Interventions

Postoperative IV PCA Ketamine 1 mg /mL

Outcomes

Pain intensity (VAS). Analgesic consumption. Adverse effects. Pain outcomes reported every 8 h up to 48 h postoperatively

Surgery type

Upper abdominal surgery

Group numbers after end of study (treatment/control)

40/40

Age of patient population (treatment/control)

38 ± 14

39 ± 12

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

A nurse not involved in the care of participants prepared study drug syringes

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Results of predefined outcomes reported

Size

High risk

40 participants per treatment arm
Kapfer 2005

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 65, of whom 43 participants in IV ketamine and control treatment arms. About 37% women

Interventions

Postoperative ketamine 10 mg bolus over a twelve‐min period. IV if preceding opioid analgesia insufficient

Outcomes

Morphine consumption. Failure of morphine titration to produce adequate analgesia. Delay between the end of morphine titration and reappearance of a VRS pain score 2 or more

Surgery type

Laparotomy, lumbotomy, orthopedic surgery (hip or knee arthroplasty)

Group numbers after end of study (treatment/control)

22/21

Age of patient population (treatment/control)

51 ± 13

49 ± 15

Notes

Different types of surgery included. Supported by NIH Grant GM 061655 (Bethesda, MD), the Gheens Foundation (Louisville, KY), the Joseph Drown Foundation (Los Angeles, CA), and the Commonwealth of Kentucky Research Challenge Trust Fund (Louisville, KY).

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation list

Allocation concealment (selection bias)

Low risk

Quote: "Randomization was based on computer‐generated codes that were maintained in sequentially numbered, opaque envelopes until just before use."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

22 and 21 participants per treatment arm
Karaman 2006

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, 100% women

Interventions

  1. Pre‐incisional ketamine 0.4 mg/kg bolus IV

  2. Ketamine 0.4 mg/kg bolus IV at wound closure

Outcomes

Pain intensity (VAS, VRS). Analgesic consumption. Time to first analgesic request. AEs. Pain outcomes reported at 1, 2, 3, 4, 8, 12 and 24 h postoperatively

Surgery type

Total abdominal hysterectomy

Group numbers after end of study (treatment/control)

40/20

Age of patient population (treatment/control)

48.2 ± 5.3

46.4 ± 3.5

Notes

Article in Turkish. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation achieved by shuffling envelopes

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Kararmaz 2003

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, 80% women

Interventions

Ketamine 0.5 mg/kg bolus IV + 0.5 mg/kg/h IV infusion until skin closure

Outcomes

Pain intensity (VAS) reported at 0.5, 1, 2, 4, 6, 12, 24 and 48 h postoperatively. Mean PCEA analgesic consumption on 1st and 2nd postoperative day. Time to first analgesic request. AEs

Surgery type

Elective renal surgery

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

36.7 ± 13.8

38.2 ± 15.4

Notes

No mention of funding or sponsorship

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random sequence

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Karcioglu 2013

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, gender of participants not presented in demographic data

Interventions

Ketamine 1 mg/kg bolus IV at anaesthesia induction + 25 mcg/kg/min IV infusion until the end of surgery

Outcomes

Pain intensity (VAS) reported at PACU discharge and at 24 h postoperatively. Analgesic consumption reported as proportion (%) of participants receiving analgesics. AEs

Surgery type

Laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

17/20

Age of patient population (treatment/control)

38.6 ± 11.7

43.4 ± 12.1

Notes

No mention of sponsorship or funding. The authors declare no conflicts of interest

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random sequence

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not reported

Incomplete outcome data (attrition bias)
All outcomes

Low risk

8% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported (three participants withdrawn from the ketamine group because of hypertension)

Size

High risk

17 and 20 participants per treatment arm
Katz 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 168, 100% men

Interventions

  1. Pre‐incisional ketamine 0.2 mg/kg bolus IV + 0.0025 mg/kg/min infusion IV for 70 mins

  2. Ketamine 0.2 mg/kg bolus IV 70 mins after the incision + 0.0025 mg/kg/min infusion IV up to 80 mins

Outcomes

Pain intensity (VAS), reported at 3, 6, 12, 24, 48 and 72 h postoperatively. Analgesic consumption reported at 0‐3, 3‐6, 6‐12, 12‐24, 24‐48 and 48‐72 h postoperatively. Touch and pain threshold (von Frey)

Surgery type

Radical prostatectomy

Group numbers after end of study (treatment/control)

97/46

Age of patient population (treatment/control)

62 ± 6.8

61 ± 6.7

Notes

The study was supported by Grants MT‐12052 and MOP‐37845 from the Canadian Institutes of Health Research (CIHR), Ontario, Canada, and a CIHR Investigator Award to the lead author.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation list

Allocation concealment (selection bias)

Low risk

Quote: "An opaque envelope containing the patient number and group assignment was prepared, sealed and numbered for each patient by the hospital pharmacist" (a third party)

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

11% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

47, 46 and 50 participants per treatment arm
Kim 2013

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, about 47% women

Interventions

  1. Pre‐incisional ketamine 0.5 mg/kg bolus IV + 1 mcg/kg/min intraoperative infusion IV until 48 h postoperatively

  2. Pre‐incisional ketamine 0.5 mg/kg bolus IV + 2 mcg/kg/min intraoperative infusion IV until 48 h postoperatively

Outcomes

Pain intensity (VAS) reported at 1, 6, 12 and 24 h postoperatively. Analgesic consumption reported at 48 h postoperatively. AEs

Surgery type

Lumbar spinal fusion surgery

Group numbers after end of study (treatment/control)

35/17

Age of patient population (treatment/control)

55.5 ± 11.8

56 ± 13

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation method not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

12% was withdrawn

Selective reporting (reporting bias)

Low risk

All predefined outcomes reported

Size

High risk

18, 17 and 17 participants per treatment arm
Kim 2016

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 58, 95% women

Interventions

After the induction on anaesthesia, ketamine bolus 1 mg/kg IV followed by a continuous infusion 60 µg/kg/h until skin closure

Outcomes

Pain intensity (NRS). Analgesic consumption. Pain outcomes reported at 1, 6, 24 and 48 h postoperatively. AEs

Surgery type

Bilateral axillo‐breast approach robotic or endoscopic thyroidectomy

Group numbers after end of study (treatment/control)

28/29

Age of patient population (treatment/control)

40 ± 9

39 ± 8

Notes

No mention of sponsorship or funding. The study authors have no conflicts of interest.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated table of random numbers (Random‐Allocation Software Version 1.0)

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel collected data

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

28 and 29 participants per treatment arm
Köse 2012

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 150, of whom 120 participants in IV ketamine and control treatment arms. About 74% women

Interventions

Ketamine 0.1 mg/kg OR ketamine 0.25 mg/kg OR ketamine 0.5 mg/kg bolus IV 20 mins before the end of surgery. Heterogeneous surgery types

Outcomes

Pain intensity (VAS) reported at 0, 1 and 2 h postoperatively. Time to first analgesic request. AEs. Postoperative shivering

Surgery type

Various operations under general anaesthesia

Group numbers after end of study (treatment/control)

90/30

Age of patient population (treatment/control)

41.2 ± 12

44.5 ± 9.2

Notes

Primary endpoint was postoperative shivering. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Low risk

Allocation in closed envelopes, identical study drug syringes prepared and labelled by an independent investigator not participating in the further study

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded investigator made assessments

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

30 participants per treatment arm
Kudoh 2002

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 70. Participants diagnosed as having major depression. Gender of participants not presented

Interventions

Pre‐incisional ketamine 1 mg/kg bolus IV

Outcomes

Pain intensity (VAS) reported every 8 h for the first 24 h, then every 24 h till 4th postoperative day. Postoperative confusion

Surgery type

Orthopedic surgery

Group numbers after end of study (treatment/control)

35/35

Age of patient population (treatment/control)

46.9 ± 8.8

48.2 ± 7.4

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

35 participants per treatment arm
Kwok 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 135, 100% women

Interventions

  1. Pre‐incisional bolus of ketamine 0.15 mg/kg IV

  2. At wound closure: ketamine bolus 0.15 mg/kg IV

Outcomes

Pain intensity (VAS) reported hourly up to 7 h postoperatively, then at 24 h. Analgesic consumption until VAS < 20 mm. AEs

Surgery type

Laparoscopic gynaecological surgery

Group numbers after end of study (treatment/control)

90/45

Age of patient population (treatment/control)

33 ± 6.1

34 ± 6

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers

Allocation concealment (selection bias)

Low risk

Allocation was concealed in opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

45 participants per treatment arm
Kwon 2009

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, 100% women

Interventions

Intraoperative ketamine 0.3 mg/kg bolus IV followed by an infusion 3 µg/kg/min

Outcomes

Pain intensity (VAS) reported at 24 and 48 h postoperatively. Analgesic consumption reported at 0‐6 h, 6‐12 h, 12‐24 h and 24‐48 h postoperatively. AEs

Surgery type

Mastectomy

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

50.5 ± 8.8

47.2 ± 7.4

Notes

Article in Korean. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not described in detail

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Prespecified outcomes reported

Size

High risk

20 participants per treatment arm
Lahtinen 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 102, about 11% women

Interventions

S‐ketamine 75 µg/kg bolus IV immediately after anaesthesia induction + intraoperative IV infusion 1.25 µg/kg/min for 48 h after arrival to the PACU

Outcomes

Pain intensity (VAS) reported after extubation, after titration of oxycodone until VAS < 30 mm, on the day of surgery at 12 pm, on first postoperative day at 8 am, 4 pm and 12 pm, on second postoperative day at 8 pm and 4 pm. Cumulative analgesic consumption at 48 h postoperatively. AEs

Surgery type

Sternotomy

Group numbers after end of study (treatment/control)

44/46

Age of patient population (treatment/control)

59 ± 5

58 ± 7

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Randomization was performed with a computer program by using random numbers and a balanced design."

Allocation concealment (selection bias)

Low risk

Mentioned: "the code remained blinded until the end of the study" and that study drug syringes were identical in appearance but not described in detail how the allocation was concealed

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

11% was withdrawn

Selective reporting (reporting bias)

Low risk

All predefined outcomes reported adequately

Size

High risk

44 and 46 participants per treatment arm
Lak 2010

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, 12% women

Interventions

Ketamine 0.5 mg/kg bolus IV postoperatively + IV infusion 2 µg/kg/min for 24 h, then 1 µg/kg/min the following 24 h

Outcomes

Pain intensity (VAS and face pain scale) reported hourly during the first 4 h, then at 8, 12, 24 and 48 h postoperatively. Analgesic consumption reported at 48 h postoperatively. AEs

Surgery type

Nephrectomy

Group numbers after end of study (treatment/control)

25/25

Age of patient population (treatment/control)

27.3 ± 5.5

27.9 ± 3.9

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Randomization was assigned to patients of the two groups according to random numbers table"

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Described as "double blind" but not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding process not described

Incomplete outcome data (attrition bias)
All outcomes

High risk

20% was withdrawn

Selective reporting (reporting bias)

High risk

Pain outcome not reported using predefined pain scale (face pain scale)

Size

High risk

25 participants per treatment arm
Leal 2013

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, about 83% women

Interventions

Ketamine 5 µg/kg/min infusion IV until wound closure

Outcomes

Pain intensity (NRS) reported every 30 min up to 4 h, then every 6 h up to 24 h postoperatively. Time to the first analgesic supplementation. Cumulative analgesic consumption reported at 24 h postoperatively. AEs

Surgery type

Laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

46 ± 12.5

45.5 ± 16.1

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation achieved by drawing envelopes

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

High risk

AEs are defined and reported in 'results' section, but not predefined in 'methods' section

Size

High risk

20 participants per treatment arm
Leal 2015

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 56, about 84% women

Interventions

Ketamine 5 µg/kg/min infusion IV until skin closure

Outcomes

Pain intensity (NRS) reported in 30‐min intervals up to 4 h, then in 6‐h intervals up to 24 h postoperatively. Analgesic consumption reported at 24 h postoperatively. Time to first morphine supplementation. Extent of hyperalgesia reported at 24 h after surgery. AEs

Surgery type

Laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

28/28

Age of patient population (treatment/control)

45.8 ± 13.1

43.4 ± 15.9

Notes

Funded by grant 2009/5335‐4, São Paulo Research Foundation and Coordenacão de Aperfeicoamento de Pessoal De Nível Superior

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation achieved by a computer program "Randomizer"

Allocation concealment (selection bias)

Low risk

Opaque, sealed envelopes contained allocation information

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Binded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7% was withdrawn

Selective reporting (reporting bias)

High risk

Adverse effects not defined in 'methods' section but are reported

Size

High risk

28 participants per treatment arm
Lebrun 2006

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 84, about 42% women

Interventions

  1. Ketamine 0.3 mg/kg bolus IV at anaesthesia induction

  2. Ketamine 0.3 mg/kg bolus IV at the end of surgery

Outcomes

Pain intensity (VAS) reported at 0.5, 1, 2, 4, 24 and 48 h postoperatively. Time to first request for analgesia. AEs. Analgesic consumption in PACU

Surgery type

Third molar surgical removal

Group numbers after end of study (treatment/control)

54/30

Age of patient population (treatment/control)

19 ± 6.7

20.7 ± 8.7

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers

Allocation concealment (selection bias)

Unclear risk

Allocation concealment not described in detail. Only mentioned that a nurse not involved in the study prepared study drugs

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel and participants

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

13% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

31, 23 and 30 participants per treatment arm
Lee 2008

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 32, about 55% women

Interventions

Pre‐incisional ketamine 0.15 mg/kg bolus IV

Outcomes

Pain intensity (NRS) reported on arrival to PACU and at 5, 10, 15 and 30 min, then at 5 and 24 h postoperatively. Analgesic consumption (either ketorolac or tramadol) reported as additional count per day

Surgery type

Laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

16/15

Age of patient population (treatment/control)

40.7 ± 7.8

43.8 ± 10.8

Notes

Article in Korean. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Study authors do not describe randomisation

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding not described, only stated "double blind" in the title

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

A blinded investigator assessed postoperative pain scores

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3% was withdrawn

Selective reporting (reporting bias)

Unclear risk

The study protocol was not available

Size

High risk

16 and 15 participants per treatment arm
Lehmann 2001

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 80, about 58% women

Interventions

Pre‐incisional bolus of ketamine 0.15 mg/kg IV

Outcomes

Pain intensity (VAS, VRS). PCA piritramide consumption. Rescue medication. AEs. Pain outcomes reported hourly up to 6 h postoperatively, then at 12 and 24 h after surgery

Surgery type

Laparotomy or proctologic surgery

Group numbers after end of study (treatment/control)

40/40

Age of patient population (treatment/control)

46 ± 12

43 ± 10

Notes

In the English abstract, the operation is laparoscopic surgery, in the original article (in German), it is said to be laparotomy. We contacted the study author and he clarified that the procedure was laparotomy or proctologic surgery. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation list

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

A person not involved in patient care prepared the study solutions

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not described

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Withdrawals not reported

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported. Results as percentage

Size

High risk

40 participants per treatment arm
Lenzmeier 2008

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 22, 100% women

Interventions

Ketamine 0.5 mg/kg bolus IV at anaesthesia induction

Outcomes

Pain intensity (VAS) reported upon admission to and at discharge from PACU. Opioid consumption during PACU stay

Surgery type

Laparoscopic abdominal procedures

Group numbers after end of study (treatment/control)

11/11

Age of patient population (treatment/control)

29.7 ± 8.5

31.6 ± 6.7

Notes

A pilot study, findings reported as descriptive statistics. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Sequence generation not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Mentioned "double‐blind" but blinding process not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

11 participants per treatment arm.
Lin 2016

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

90, 100% women

Interventions

Pre‐incisional ketamine 0.3 mg/kg bolus IV

Outcomes

Pain intensity (VAS) reported at 2, 6, 12 and 24 h postoperatively. Mean analgesic dose per participant. Time to first analgesic request. AEs

Surgery type

Gynecological laparoscopic surgery

Group numbers after end of study (treatment/control)

30/29

Age of patient population (treatment/control)

39.6 ± 9.8

43.4 ± 10.1

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation method not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Only mentioned double‐blind with no further description

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Not described in detail

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2% was withdrawn

Selective reporting (reporting bias)

High risk

Results of time to first request for analgesia are reported but this outcome was not predefined in methods

Size

High risk

29 and 30 participants per treatment arm
Lo 2008

Study characteristics

Methods

Randomised, double‐blind. Ketamine + morphine vs morphine

Participants

N = 30, 100% women

Interventions

Ketamine 2 mg /bolus via IV‐PCA postoperatively

Outcomes

Pain intensity (VAS) reported at 24 h and 48 h postoperatively. Analgesic consumption reported at 48 h postoperatively. AEs

Surgery type

Abdominal hysterectomy

Group numbers after end of study (treatment/control)

15/15

Basis for group size unclear (power analysis not presented). Study authors state that the study was underpowered because of cessation of the recruitment by a labour disruption

Age of patient population (treatment/control)

Mean values without standard deviations reported

49.2

47.4

Notes

Study not sufficiently powered because of interruption by a labour disruption. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation achieved by selecting envelopes

Allocation concealment (selection bias)

Low risk

Group allocation was enclosed in sealed envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Unclear risk

Time frame for mean analgesic consumption unclear

Size

High risk

15 participants per treatment arm
Loftus 2010

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 101, about 40% women

Interventions

Ketamine 0.5 mg/kg bolus IV on anaesthesia induction + infusion 10 µg/kg/min IV until wound closure

Outcomes

Pain intensity (VAS). Analgesic consumption. AEs.

Outcomes reported at 24 and 48 h, and 6 weeks

Surgery type

Major lumbar spine surgery

Group numbers after end of study (treatment/control)

52/50

Age of patient population (treatment/control)

51.7 ± 14.2

51.4 ± 14.4

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated block randomisation scheme

Allocation concealment (selection bias)

Low risk

The study infusions were prepared by the investigational pharmacy (a third party) preoperatively and labelled as "study drug/placebo"

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Less than 10% of the data pertaining to the primary outcome were missing in the final analysis. Missing data were due to unanticipated early participant discharge with equal numbers in both treatment groups. No participants enrolled in the study were excluded from the primary analysis

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported adequately

Size

Unclear risk

50 and 52 participants per treatment arm
Mahran 2015

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 90, of whom 60 participants in IV ketamine and control treatment arms. 100% women

Interventions

Ketamine 0.5 mg/kg bolus IV before anaesthesia induction + intraoperative IV infusion 0.25 mg/kg/h till the end of skin closure

Outcomes

Pain intensity (VAS) reported at 30 min, 2, 4, 6, 12 and 24 h postoperatively. Cumulative analgesic consumption at 24 h. AEs

Surgery type

Breast cancer surgery (radical mastectomy)

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

53.1 ± 6.2

53.9 ± 8.1

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number assignment

Allocation concealment (selection bias)

Low risk

Allocation concealed in sequentially numbered, opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

All predefined dropouts reported

Size

High risk

30 participants per treatment arm
Martinez 2014

Study characteristics

Methods

Randomised, double‐blind. Ketamine vs placebo. Ketamine vs pregabalin

Participants

N = 142. Total hip arthroplasty under general anaesthesia. About 48% women

Interventions

Ketamine 0.5 mg/kg bolus IV at induction + 3 µg/kg/min IV infusion until skin closure

Outcomes

Pain intensity (NRS) reported in the recovery room, at 24 and 48 h. Analgesic consumption at 48 h. Pressure pain threshold measured on the first and second postoperative days. AEs

Surgery type

Total hip arthroplasty

Group numbers after end of study (treatment/control)

Ketamine: 34

Placebo: 38

Ketamine + pregabalin 35

Pregabalin: 35

Age of patient population (treatment/control)

60 ± 17

64 ± 11

64 ± 9

59 ± 12

Notes

Divided into 2 for analysis: ketamine vs placebo and ketamine + pregabalin vs pregabalin. No external funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers

Allocation concealment (selection bias)

Low risk

Allocation concealed in opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Study solutions were prepared by an independent person.

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

13% was withdrawn

Selective reporting (reporting bias)

Low risk

All predefined outcomes reported adequately

Size

High risk

34, 38, 35 and 35 participants per treatment arm.
Mathisen 1999

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, about 82% women

Interventions

  1. Pre‐incisional bolus of R‐ketamine 1 mg /kg IV

  2. IV‐bolus of R‐ketamine 1 mg/kg at wound closure

Outcomes

Pain intensity (VAS, VRS) reported at 1, 2, 3, 4 and 24 h and 7 days after surgery. PCA opioid consumption reported at 1, 2, 3 and 4 h postoperatively. Analgesics after discharge. AEs

Surgery type

Elective laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

32/18

Age of patient population (treatment/control)

48 ± 15.8

50 ± 13

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not described

Allocation concealment (selection bias)

Low risk

Central allocation

Quote: "The hospital pharmacy prepared the drugs in identical ampules marked with patient number and injection number in a randomized, double‐blind manner."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

17% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
McKay 2007

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 41, about 46% women

Interventions

Pre‐incisional ketamine 1.5 mg/kg bolus IV followed by ketamine infusion 2.5 µg/kg/min

Outcomes

Pain intensity (VAS; reported as AUC: units (cm) x half days). AEs. Return of bowel function. Time to ambulation. Length of hospital stay. Analgesic consumption reported as total opioid use for each study participant, time frame unclear

Surgery type

Laparotomy (bowel resection)

Group numbers after end of study (treatment/control)

19/22

Age of patient population (treatment/control)

49.5 ± 16.3

51.8 ± 12.8

Notes

Primary outcome was return of bowel function. The study was funded in part by a grant from the Royal University Hospital Foundation, Saskatoon, Canada

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random number table

Allocation concealment (selection bias)

Low risk

Central allocation. Hospital pharmacy (a third party) randomised participants and prepared study drug solutions

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

19 and 22 participants per treatment arm
Mebazaa MS 2008

Study characteristics

Methods

Randomised, double‐blind. Ketamine + morphine vs morphine

Participants

N = 138, about 49% women

Interventions

Ketamine 1 mg/bolus IV via PCA

Outcomes

Pain intensity (VAS). Analgesic consumption. AEs. Outcomes reported every 4 h up to 48 h postoperatively

Surgery type

Laparotomy

Group numbers after end of study (treatment/control)

67/67

Age of patient population (treatment/control)

46 ± 13

46 ± 14

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation was stratified according to the type of surgery (i.e. visceral or gynaecological) and performed according to a table of random numbers per blocks of six

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

Unclear risk

67 participants per treatment arm
Mendola 2012

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 66, about 32% women

Interventions

S‐ketamine 0.1 mg/kg/h infusion IV during surgery and for 60 h postoperatively

Outcomes

Pain intensity (NRS) on 1st, 2nd and 3rd day postoperatively and then monthly up to 6 months. Analgesic consumption reported on 1st, 2nd and 3rd days postoperatively. AEs. NPSI at 1, 3 and 6 months postoperatively

Surgery type

Thoracotomy

Group numbers after end of study (treatment/control)

32/30

Age of patient population (treatment/control)

62 ± 10.4

65.7 ± 10.9

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation achieved by the statistic laboratory of the institution

Allocation concealment (selection bias)

Low risk

Central allocation. Hospital pharmacy (a third party) prepared the study infusions that were coded

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

6% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes addressed

Size

High risk

32 and 30 participants per treatment arm
Menigaux 2000

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 45, about 33% women

Interventions

Ketamine 0.15 mg/kg bolus IV before surgical incision or at wound closure

Outcomes

Pain intensity (VAS, VRS) reported at 1, 2, 3 h, then every 4 h up to 48 h after surgery. PCA morphine consumption. Incremental doses reported hourly up to 3 h postoperatively, then every 4 h up to 48 h. Cumulative morphine consumption reported at 24 and 48 h after surgery. AEs. Time to first analgesic request

Surgery type

Elective arthroscopic anterior cruciate ligament repair

Group numbers after end of study (treatment/control)

30/15

Age of patient population (treatment/control)

26 ± 6

28 ± 7

Notes

No mention of sponsorship or funding

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

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel at data collection

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes clearly reported

Size

High risk

15 participants per treatment arm
Menigaux 2001

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 50, 34% women

Interventions

Pre‐incisional bolus of ketamine 0.15 mg/kg IV

Outcomes

Pain intensity (VAS, VRS) reported every 15 mins for 1 h, then every 2 h up to 6 h after surgery and on 1st, 2nd and 3rd day after surgery. Rescue medication (mean number of analgesic tablets per participant required during 3 days). AEs

Surgery type

Outpatient knee arthroscopy

Group numbers after end of study (treatment/control)

25/25

Age of patient population (treatment/control)

37 ± 9

36 ± 12

Notes

Supported by NIH Grant GM 58273, the Joseph Drown Foundation, and the Commonwealth of Kentucky Research Challenge Trust Fund

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated random number table

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

25 participants per treatment arm
Michelet 2007

Study characteristics

Methods

Randomised, double‐blind. Ketamine + morphine vs morphine

Participants

N = 50, 28% women

Interventions

Ketamine 1 mg/mL via IV PCA

Outcomes

Pain intensity (VAS) and cumulative analgesic consumption, reported at baseline, at 12, 24, 36, 48 and 60 h postoperatively. AEs

Surgery type

Thoracotomy

Group numbers after end of study (treatment/control)

24/24

Age of patient population (treatment/control)

Mean (range)

64 (42‐77)

63 (42‐76)

Notes

No financial support

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Table of random numbers

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail. Only mentioned that a hospital pharmacist prepared study drugs

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

4% was withdrawn

Selective reporting (reporting bias)

Low risk

Results of predefined outcomes reported

Size

High risk

24 participants per treatment arm
Miziara 2016

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 48, patient demographic data table not presented

Interventions

S‐ketamine infusion 5 µg/kg/min beginning 5 mins before surgery and lasting till the end of surgery

Outcomes

Pain intensity (VNS 0‐10) reported during PACU stay, at 4 and 12 h postoperatively. Analgesic consumption reported during PACU stay, at 4‐12 h and as cumulative analgesic consumption at 12 h postoperatively. AEs

Surgery type

Laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

24/21

Age of patient population (treatment/control)

No data available

Notes

No mention of sponsorship or funding. Study authors state that they have no conflicts interest

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation achieved using a randomisation software

Allocation concealment (selection bias)

Low risk

Allocation sequence was concealed in sequentially numbered, sealed envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

7% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

21 participants per treatment arm
Murdoch 2002

Study characteristics

Methods

Randomised, double‐blind. Ketamine + morphine vs morphine

Participants

N = 42, 100% women

Interventions

Postoperative IV PCA ketamine 0.75 mg/bolus + morphine

Outcomes

Pain intensity (VRS), reported every 4 h up to 16 h postoperatively, then at 24 h. PCA morphine consumption reported at 24 h. AEs

Surgery type

Total abdominal hysterectomy

Group numbers after end of study (treatment/control)

21/19

Age of patient population (treatment/control)

43.2 ± 6.6

41.8 ± 8.8

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

5% was withdrawn

Selective reporting (reporting bias)

Unclear risk

Predefined outcomes reported but only P values

Size

High risk

21 and 19 participants per treatment arm
Nesek‐Adam 2012

Study characteristics

Methods

Randomised, double‐blind

Participants

N = 80, about 73% women

Interventions

  1. Pre‐incisional ketamine 0.15 mg/kg bolus IV vs placebo

  2. Pre‐incisional ketamine 0.15 mg/kg + diclofenac 1 mg/kg bolus IV vs pre‐incisional diclofenac 1 mg/kg IV

Outcomes

Pain intensity (VAS), reported every 2 h up to 6 h postoperatively, then at 12 and 24 h. Time to first analgesic request. AEs

Surgery type

Laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

20/20/20/20

Age of patient population (treatment/control)

Ketamine group 50.7 ± 11.9

Placebo group 53.6 ± 9.6

Diclofenac group 45.7 ± 15.3

Ketamine + diclofenac group 52.7 ± 15.5

Notes

4 treatment arms. Ketamine vs placebo and ketamine + diclofenac vs diclofenac. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated random number table

Allocation concealment (selection bias)

Low risk

Quote: "An envelope containing group assignment was prepared, sealed, and numbered for each patient."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Nielsen 2017

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 150, 65% women

Interventions

Intraoperative S‐ketamine bolus 0.5 mg/kg and infusion 0.25 mg/kg/h

Outcomes

Analgesic consumption, reported at the first hour in the PACU and then at 24 h. Postoperative pain intensity (VAS), reported every 2 h up to 24 h postoperatively at rest and during mobilisation. AEs (PONV reported every 6 h up to 24 h postoperatively, CNS AEs reported as number of participants experiencing CNS adverse event during 0‐24 h). Persistent pain 6 months postoperatively

Surgery type

Lumbar fusion surgery

Group numbers after end of study (treatment/control)

75/75

Age of patient population (treatment/control)

57 ± 14

55 ± 13

Notes

The study was supported by the Department of Neuroanesthesiology Rigshospitalet, Glostrup, Copenhagen University Hospital

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated randomisation list

Allocation concealment (selection bias)

Low risk

Central allocation. Hospital pharmacy (a third party) prepared and pre‐packed identical ampoules in consecutively numbered boxes according to the computer‐generated randomisation list. Information about each participant's treatment was concealed in consecutively numbered, sealed, opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3% was withdrawn in the immediate postoperative period

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

Unclear risk

75 participants per treatment arm
Ögün 2001

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 47, 100% women

Interventions

Ketamine 1 mg/kg bolus IV pre‐incisionally and after excision of tissue specimen

Outcomes

Pain intensity (VAS, VRS) reported at 0, 1, 2, 4, 6, 12 and 24 h postoperatively. Analgesic consumption reported at 24 h postoperatively. AEs

Surgery type

Mastectomy

Group numbers after end of study (treatment/control)

16/15

Age of patient population (treatment/control)

47.2 ± 12.7

47.8 ± 14.2

Notes

Article in Turkish. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment process not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Only mentioned double‐blind but lacks description of how it was achieved

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Only mentioned double‐blind but lacks description of how it was achieved

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

15 and 16 participants per treatment arm
Ong 2001

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, gender of participants not specified

Interventions

Ketamine 0.3 mg/kg bolus IV prior to induction

Outcomes

Pain intensity (VAS) reported on arrival to PACU, at 1 h postoperatively and on discharge. Analgesic requirement during PACU stay. AEs

Surgery type

Extraction of wisdom teeth

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

24.1 ± 15.3

24.1 ± 6.6

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation by drawing cards from an envelope

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Ozhan 2013

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, about 82% women

Interventions

Pre‐incisional ketamine 0.25 mg/kg bolus IV

Outcomes

Analgesic consumption at 24 h postoperatively. Preoperative and postoperative cognitive function (Mini‐Mental Test). AEs. Recovery time

Surgery type

Laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

46 ± 12.3

47 ± 11.5

Notes

No mention of sponsorship or funding. The study authors declare that they have no competing interests

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated list of random numbers

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

30 participants per treatment arm
Pacreu 2012

Study characteristics

Methods

Randomised, double‐blind. Intraoperative ketamine + postoperative IV‐PCA containing ketamine + methadone VS intraoperative placebo + postoperative IV‐PCA with methadone alone

Participants

N = 22, 70% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV + intraoperative ketamine 2.5 µg/kg/min infusion IV + postoperative IV‐PCA 0.5 mg/bolus

Outcomes

Pain intensity (NRS). Analgesic consumption. AEs

Main outcomes at 24 and 48 h

Surgery type

Lumbar arthrodesis

Group numbers after end of study (treatment/control)

10/10

Age of patient population (treatment/control)

52.9 ± 12.6

61.3 ± 11.7

Notes

Institutional support

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated randomisation list was performed by the Department of Biostatististics

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

9% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

10 participants per treatment arm
Papaziogas 2001

Study characteristics

Methods

Randomised, double‐blind. Ketamine IV + ropivacaine SC vs ropivacaine SC

Participants

N = 55, of whom 35 participants in IV ketamine and control treatment arms

Interventions

Pre‐incisional bolus of ketamine 1 mg/kg IV

Outcomes

Pain intensity (VAS, VRS) reported at baseline, at 3, 6, 12, 24 and 48 h postoperatively. Analgesic consumption reported at 48 h postoperatively. Rescue analgesia. Time to first request for analgesia. AEs

Surgery type

Elective laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

18/17

Age of patient population (treatment/control)

41.3 ± 13.6

47.9 ± 16.7

Notes

Third group received saline IV and saline SC. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding process not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding process not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

4% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

18, 17 and 18 participants per treatment arm
Parikh 2011

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, about 38% women

Interventions

Ketamine 0.15 mg/kg bolus IV 30 min before start of surgery + 2 µg/kg/min infusion IV till start of skin closure

Outcomes

Pain intensity (VAS), reported at 15, 30 and 60 min after surgery, then every 4 h up to 16 h and finally at 24 h postoperatively. Time to first analgesic request. Analgesic consumption reported at 24 h postoperatively. AEs

Surgery type

Open renal surgery by flank incision

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

39.2 ± 12.2

42.2 ± 10.5

Notes

No financial support

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation by shuffling envelopes

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded observers

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

30 participants per treatment arm
Patel 2016

Study characteristics

Methods

Randomised, double‐blind. Ketamine + clonidine vs clonidine

Participants

N = 75, of whom 50 participants in IV ketamine and control treatment arms. 10% women

Interventions

Ketamine 1 mg/kg bolus IV during induction of anaesthesia

Outcomes

Pain intensity (VAS) reported at 4, 8, 12 and 24 h postoperatively. Analgesic consumption reported as number of doses at 24 h. Intraoperative haemodynamic parameters

Surgery type

Off‐pump coronary artery bypass

Group numbers after end of study (treatment/control)

25/25

Age of patient population (treatment/control)

60.91 ± 6.17

58.52 ± 8.29

Notes

No funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated randomisation list

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

25 participants per treatment arm
Pirim 2006

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 45, 100% women

Interventions

Postoperative ketamine infusion initially 10 mg/kg/min IV and gradually lowered to 2.5 mg/kg/min for 24 h postoperatively

Outcomes

Pain intensity (VAS, VRS). Analgesic consumption. Pain outcomes reported at 1, 2, 4, 6, 12 and 24 h postoperatively. AEs reported at 24 and 48 h postoperatively

Surgery type

Total abdominal hysterectomy

Group numbers after end of study (treatment/control)

23/22

Age of patient population (treatment/control)

46.7 ± 6

45.9 ± 5.5

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described in detail

Allocation concealment (selection bias)

Low risk

Allocation concealed in envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Not described

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Assessments made by a researcher who was unaware of the study groups

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

22 and 23 participants per treatment arm
Remérand 2009

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 154, 49% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV + 2 µg/kg/min infusion IV for 24 h

Outcomes

Pain intensity (NRS) reported on 1st and 2nd day postoperatively. Analgesic consumption reported at PACU, at 24 and 48 h postoperatively and on days 4 and 7 postoperatively. AEs

Surgery type

Total hip arthroplasty

Group numbers after end of study (treatment/control)

79/75

Age of patient population (treatment/control)

64 ± 13

65 ± 14

Notes

Supported by institutional and/or departmental sources

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation process

Allocation concealment (selection bias)

Low risk

Quote: "Before the study began, as part of a computer‐generated randomization process, 160 identical white envelopes were prepared, numbered, and sealed by a person external to our clinical unit. Each envelope contained detailed instructions of the preparation of 2 syringes (ketamine or saline)."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals in the immediate postoperative period. At 6 months, 8% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported adequately

Size

Unclear risk

79 and 74 participants per treatment arm
Reza 2010

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, 100% women

Interventions

Ketamine 0.5 mg/kg bolus IV before anaesthesia induction

Outcomes

Pain intensity (VAS), reported at 2, 6, 12 and 24 h postoperatively. Analgesic consumption, reported at 0‐2 h and 2‐24 h postoperatively. AEs

Surgery type

Elective caesarean section

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

27 ± 5.1

27 ± 4.5

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers

Allocation concealment (selection bias)

Low risk

Allocation was concealed in opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes adequately addressed

Size

High risk

30 participants per treatment arm
Roytblat 1993

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 22, 100% women

Interventions

Pre‐incisional bolus of ketamine 0.15 mg/kg IV

Outcomes

Pain intensity (VAS, VRS). PCA morphine consumption. Time to first request for analgesia. AEs. Pain outcomes recorded at 1, 2, 3, 4, 5, 6, 12 and 24 h after surgery

Surgery type

Elective open cholecystectomy

Group numbers after end of study (treatment/control)

11/11

Age of patient population (treatment/control)

55.1 ± 10.7

54.8 ± 14.8

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

All participants and personnel involved in patient management were unaware of the group to which the participant had been assigned

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Personnel involved in data collection were blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

11 participants per treatment arm
Safavi 2011

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 120, of whom 60 participants in IV ketamine and control treatment arms. About 48% women

Interventions

Pre‐incisional ketamine 1 mg/kg bolus IV

Outcomes

Pain intensity (VAS), reported at 15 and 30 min, then at 1, 2, 3, 4, 8, 12 and 24 h postoperatively. Analgesic consumption reported at 24 h postoperatively. Time to first request for rescue analgesia. AEs

Surgery type

Open cholecystectomy

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

47.7 ± 11.8

54.1 ± 11.3

Notes

Four study groups in the study: 1 group where participants received ketamine IV, 2 groups where ketamine was given SC in different doses and 1 control group where the participants received saline. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Low risk

A research nurse prepared envelopes that were sealed, numbered and stored in a box

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcome adequately addressed

Size

High risk

30 participants per treatment arm
Sahin 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 47, of whom 33 participants in IV ketamine and control treatment arms. About 52% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV

Outcomes

Pain intensity (VAS), reported in 15‐min intervals during the 1st h. Cumulative analgesic consumption reported at 24 h postoperatively. Time to first analgesic request. AEs

Surgery type

Lumbar discectomy

Group numbers after end of study (treatment/control)

17/16

Age of patient population (treatment/control)

46.5 ± 7.3

48.3 ± 11.2

Notes

3 study groups. The treatment group received ketamine bolus IV + remifentanil intraoperatively. The 2nd group where participants received saline bolus IV + remifentanil intraoperatively served as a control group. The 3rd group (14 participants) received saline bolus IV + saline infusion intraoperatively and was excluded from the analysis. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Unclear risk

Predefined outcomes reported but misses exact numbers of PONV, only mentioned that the incidences of nausea, vomiting were similar among groups

Size

High risk

17 and 16 participants per treatment arm
Sen 2009

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, 100% women

Interventions

Pre‐incisional ketamine 0.3 mg/kg bolus IV + 0.05 mg/kg/h infusion IV until the end of surgery

Outcomes

Pain intensity (VRS). Analgesic consumption. AEs. Main outcomes reported every 4 h up to 24 h postoperatively

Surgery type

Abdominal hysterectomy

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

46 ± 6

46 ± 7

Notes

The third group in this study was treated with oral gabapentin. Supported by institutional and departmental sources at GATA Haydarpasa Eğitim Hastanesi.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated table of random numbers

Allocation concealment (selection bias)

Low risk

Central allocation: hospital pharmacy (a third party) prepared study drugs that were labelled identically

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported adequately

Size

High risk

20 participants per treatment arm
Siddiqui 2015

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, gender of participants not specified

Interventions

Ketamine 0.3 mg/kg bolus IV following induction

Outcomes

Pain intensity (VAS) reported at 30 min postoperatively as number of participants with VAS‐score 1‐3, 4‐5, 6‐8 and 9‐10, respectively. Analgesic consumption during recovery room stay. AEs

Surgery type

Elective day care surgery (procedures not defined)

Group numbers after end of study (treatment/control)

29/29

Age of patient population (treatment/control)

36.1 ± 10.6

36.1 ± 9

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described in detail

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Blinding method not described in detail

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding method not described in detail

Incomplete outcome data (attrition bias)
All outcomes

High risk

Discrepancy between text, "there were no dropouts" and a results table

Selective reporting (reporting bias)

High risk

All predefined outcomes are not reported (rescue analgesia)

Size

High risk

29 participants per treatment arm
Singh 2013

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 80. Only mentioned that adult patients of either gender were randomised

Interventions

  1. Pre‐incisional ketamine 1 mg/kg bolus IV

  2. Pre‐incisional ketamine 0.75 mg/kg bolus IV

  3. Pre‐incisional ketamine 0.5 mg/kg bolus IV

Outcomes

Pain intensity (VAS), reported every 30 min for first 2 h, every 1 h for the next 4 h, and then at 12 h and 24 h postoperatively. Time to first request for analgesia. Analgesic consumption, reported as mean number of analgesic doses given to participants in different groups. AEs

Surgery type

Laparoscopic cholecystectomy

Group numbers after end of study (treatment/control)

20/20/20/20

Age of patient population (treatment/control)

NA

Notes

3 groups with 3 different ketamine doses given pre‐incisionally IV vs placebo. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers

Allocation concealment (selection bias)

Low risk

Allocation was concealed in sealed, opaque envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Withdrawals not reported

Selective reporting (reporting bias)

Unclear risk

No numerical results but percentages reported. Withdrawals not reported

Size

High risk

20 participants per treatment arm
Snijdelaar 2004

Study characteristics

Methods

Randomised, double‐blind. Intraoperative S‐ketamine vs placebo/postoperative S‐ketamine + morphine vs morphine and placebo

Participants

N = 28. Radical retropubic prostatectomy. 100% men

Interventions

Intraoperative S‐ketamine 0.1 mg/kg bolus IV followed by a continuous infusion of 2 µg/kg/min IV until skin closure + postoperative IV PCA S‐ketamine 0.5 mg/bolus

Outcomes

Pain intensity (VAS) reported hourly up to 4 h, then at 8 and 12 h, then every 6 h up to 48 h postoperatively. PCA morphine consumption, reported hourly during the first 4 h, then every 6 h up to 48 h postoperatively. Hyperalgesia (pain perception threshold, pressure algometry). AEs

Surgery type

Radical retropubic prostatectomy

Group numbers after end of study (treatment/control)

13/12

Age of patient population (treatment/control)

60.1 ± 4.7

61.7 ± 4.7

Notes

Dr D G Snijdelaar is supported by an Independent Investigator Grant from Parke‐Davis (now Pfizer). Dr J. Katz is supported by a Canada Research Chair in Health Psychology at York University from the Canadian Institutes of Health Research.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation by using the random function of Microsoft EXCEL 97

Allocation concealment (selection bias)

Low risk

Central allocation. Study syringes prepared and dispensed by the hospital pharmacy (a third party). Coded syringes that were prepared in a blinded fashion for each participant and retained by the pharmacy

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel prepared study drugs

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel collected data

Incomplete outcome data (attrition bias)
All outcomes

High risk

11% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

13 and 12 participants per treatment arm
Song 2013

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 50, 100% women

Interventions

Ketamine 0.3 mg/kg bolus IV at induction + postoperative IV‐PCA with ketamine 3 mg/kg, background infusion 2 mL/h + 2 mL/bolus on‐demand

Outcomes

Pain intensity (VAS) reported at 0‐6 h, 6‐12 h, 12‐24 h, 24‐36 h and 36‐48 h postoperatively. Cumulative volume of IV‐PCA consumed reported at 6, 12, 24, 36 and 48 h postoperatively. AEs

Surgery type

Lumbar spinal fusion

Group numbers after end of study (treatment/control)

24/25

Age of patient population (treatment/control)

Mean (range)

57 (30‐65)

58 (34‐65)

Notes

Financial support provided from departmental sources

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number table

Allocation concealment (selection bias)

Low risk

Sequentially numbered, opaque, sealed envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2% was withdrawn

Selective reporting (reporting bias)

Low risk

Results of predefined outcomes reported

Size

High risk

24 and 25 participants per treatment arm
Song 2014

Study characteristics

Methods

Randomised, double‐blind

Participants

N = 75, 100% women

Interventions

Pre‐incisional ketamine 0.25 mg/kg bolus IV followed by an infusion of 5 µg/kg/min until skin closure

Outcomes

Pain intensity (VAS), reported at 1 h postoperatively. Cumulative analgesic consumption reported at 24 h postoperatively. Time to first request for analgesia. Hyperalgesia reported at 24 h postoperatively

Surgery type

Laparoscopic gynaecologic surgery

Group numbers after end of study (treatment/control)

25/25

Age of patient population (treatment/control)

48.9 ± 6.8

49.3 ± 5.7

Notes

The study was supported by Wonkwang University

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation according to computer‐generated random number table

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Participants unaware of group assignments. Not described whether anaesthesiologists in the operating room were blinded, thus unclear risk of bias

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded anaesthesiologist assessed pain

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

25 participants per treatment arm
Spreng 2010

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 83, 58% women of those included

Interventions

Pre‐incisional S‐ketamine 0.35 mg/kg bolus IV + 5 µg/kg/min infusion IV until 2 mins after the end of surgery

Outcomes

Pain intensity (VAS). Emergence time. AEs

Main measurements were 1 day, 7 days, and 3 months

Surgery type

Ambulatory haemorrhoidectomy

Group numbers after end of study (treatment/control)

39/38

Age of patient population (treatment/control)

46.4 ± 4.7

61.7 ± 4.7

Notes

Institutional funding, with no conflicts of interest

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Permuted block randomisation

Allocation concealment (selection bias)

Low risk

Central allocation by the hospital pharmacy.

Quote: "Permuted block randomization, blinding and packing of the study medication were performed by the hospital pharmacy. The randomization codes were provided in sealed envelopes which only were opened in case of emergency or after completion of the study protocol of all study participants."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

8% was withdrawn

Selective reporting (reporting bias)

Unclear risk

Study authors state that treatment group had more AEs. However, the difference was not statistically significant

Size

High risk

39 and 38 participants per treatment arm
Stubhaug 1997

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 20, 50% women

Interventions

Ketamine 0.5 mg/kg bolus IV + infusion 2 µg/kg/min IV for 24 h, thereafter 1 mcg/kg/min and maintained for 48 h

Outcomes

Pain intensity (VAS) reported hourly during the first 4 h. Cumulative PCA morphine consumption reported at 0‐24 h, 24‐48 h and 48‐72h postoperatively. Area of punctate hyperalgesia reported on days 1, 3 and 7 postoperatively. Pressure pain threshold. AEs

Surgery type

Nephrectomy (live kidney donors)

Group numbers after end of study (treatment/control)

10/10

Age of patient population (treatment/control)

Median (range)

44 (32‐53)

42 (25‐66)

Notes

Baxter Norway provided Baxter Ambulatory PCA Pumps with printer. No mention of additional funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random numbers (Moses Oakford algorithm)

Allocation concealment (selection bias)

Low risk

Quote: "Treatment allocation remained concealed to patients and investigators during the whole study. Study drug for each patient was prepared by the hospital pharmacy in identical containers, marked with consecutive patient numbers only and delivered by a portable pump via a separate i.v. line."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

10 participants per treatment arm
Subramaniam 2011

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 38, 50% women

Interventions

Ketamine 0.1 mg/kg bolus IV at anaesthesia induction + 2 µg/kg/min intraoperative infusion IV and 24 h postoperatively

Outcomes

Pain intensity (VAS) and analgesic consumption reported at 1, 2, 4, 8, 12, 18, 24, 36 and 48 h postoperatively. AEs

Surgery type

Lumbar or thoracolumbar laminectomy and fusion

Group numbers after end of study (treatment/control)

15/15

Age of patient population (treatment/control)

57.2 ± 12.2

56.5 ± 13.6

Notes

The study was underpowered. According to power analysis, 26 participants per study group should have been recruited in order to obtain sufficient power. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated random numbers

Allocation concealment (selection bias)

Low risk

Central allocation. Randomisation and allocation concealment by the hospital pharmacy (a third party)

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

21% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes adequately reported

Size

High risk

15 participants per treatment arm
Suzuki 1999

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 140, about 38% women

Interventions

IV‐bolus of ketamine at wound closure:

  1. 50 µg/kg

  2. 75 µg/kg

  3. 100 µg/kg

Outcomes

Pain intensity (VAS) reported at 15‐min intervals for the first hour. Rescue medication, reported as mean amount needed during the phase 1 recovery. AEs

Surgery type

Elective outpatient surgery (inguinal hernia repair, excision of skin lesions, breast or lymph node biopsy)

Group numbers after end of study (treatment/control)

105/35

Age of patient population (treatment/control)

36 ± 11

30 ± 12

Notes

3 different doses of ketamine IV vs placebo. 35 participants in each study group. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation schedule

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

A person not involved in the study prepared study drugs

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

35 participants per treatment arm. Heterogeneous procedures
Suzuki 2006

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 50, about 41% women

Interventions

Ketamine 5 µg/kg/min IV infusion after tracheal intubation lasting 72 h after surgery

Outcomes

Pain intensity (VAS) reported at 6, 12, 24 and 48 h postoperatively. Cumulative analgesic consumption reported at 0‐6 h, 6‐12 h, 12‐24 h and 24‐48 h after surgery. Abnormal sensation of pain around the wound on postoperative day 7. AEs.

Surgery type

Thoracotomy

Group numbers after end of study (treatment/control)

24/25

Age of patient population (treatment/control)

66 ± 14

66 ± 9

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Patients were assigned to one of two groups using a computer‐generated randomization schedule"

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail. Only stated that the study drugs were prepared and placed in the infusion pump by an investigator who did not participate in the administration of anaesthesia or the evaluation of postoperative pain.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

2% was withdrawn

Selective reporting (reporting bias)

Unclear risk

Predefined outcomes reported. Epidural infusion was suspended in some participants (ketamine 3, control 5) due to hypotension.

Size

High risk

24 and 25 participants per treatment arm
Tena 2014

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 125, of whom 68 participants in IV ketamine and control treatment arms. About 28% women

Interventions

Pre‐incisional ketamine 0.5 mg/kg bolus IV + postoperatively 0.25 mg/kg/h infusion IV for 48 h

Outcomes

Pain intensity (VAS) reported at 2, 4, 24 and 72 h and 3 days, 3 months and 6 months postoperatively. Hyperalgesia (von Frey filaments, electronic von Frey, electrical toothbrush) reported at 72 h, 7 days, 3 months and 6 months postoperatively. AEs

Surgery type

Thoracotomy

Group numbers after end of study (treatment/control)

33/35

Age of patient population (treatment/control)

62.9 ± 9.8

66.5 ± 9.9

Notes

The 3rd study group was not included in analysis because participants received ketamine epidurally. No mention of sponsorship or funding and the authors declare no conflict of interest

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

High risk

17% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

33 and 35 participants per treatment arm
Ünlügenc 2003

Study characteristics

Methods

Randomised, double‐blind. Ketamine + morphine vs morphine

Participants

N = 90, of whom 60 participants in IV ketamine and control treatment arms. About 43% women

Interventions

Postoperative IV PCA ketamine 0.0125 mg/kg/bolus + morphine

Outcomes

Pain intensity (VRS). PCA morphine consumption. Pain outcomes reported at 15 and 30 min, then at 1, 2, 6, 12 and 24 h postoperatively. AEs

Surgery type

Major abdominal surgery

Group numbers after end of study (treatment/control)

30/28

Age of patient population (treatment/control)

52 ± 4

51 ± 1.1

Notes

3 study groups in this study. We excluded the 3rd group from the analysis because the participants also received magnesium sulphate and the 2 other study groups did not. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

3% was withdrawn

Selective reporting (reporting bias)

High risk

All predefined AEs are not reported

Size

High risk

30, 28 and 29 participants per treatment arm
Van Elstraete 2004

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, 50% women

Interventions

Ketamine 0.5 mg/kg bolus IV after anaesthesia induction + 2 µg/kg/min infusion IV till the end of surgery

Outcomes

Pain intensity (VAS). Analgesic consumption. Time to first request for analgesia. AEs

Main outcomes at 2, 4, 8, 12, and 24 h postoperatively

Surgery type

Elective tonsillectomy

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

29 ± 7

29 ± 10

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Quote: "Patients were randomly assigned to one of two groups using a table of computer‐generated random numbers."

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail. Only stated that a research nurse not involved in the perioperative care of the participant prepared and labelled 2 syringes per randomisation list

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Quote: "The anaesthetist who was in charge of the patient during surgery was unaware of the study group assignment, as were those involved in data collection."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Quote: "The anaesthetist who was in charge of the patient during surgery was unaware of the study group assignment, as were those involved in data collection."

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

20 participants per treatment arm
Webb 2007

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 120, about 38% women

Interventions

Ketamine 0.3 mg/kg bolus IV at anaesthesia induction + intraoperative infusion 0.1 mg/kg/h for 48 h after surgery

Outcomes

Pain intensity (VRS) and analgesic consumption reported every 4 h up to 48 h postoperatively. AEs. Subjective analgesic efficacy

Surgery type

Laparotomy

Group numbers after end of study (treatment/control)

52/58

Age of patient population (treatment/control)

63 ± 15

61 ± 15

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number tables

Allocation concealment (selection bias)

Low risk

Quote: "Allocation to treatment group was determined in advance according to tables of random numbers and concealed from patients and hospital staff, using sealed opaque envelopes."

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

8% withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

Unclear risk

56 and 64 participants per treatment arm
Woo 2014

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 40, about 33% women

Interventions

Pre‐incisional ketamine 0.3 mg/kg bolus IV + continuous infusion 0.15 mg/kg/min until 5 mins before the end of surgery

Outcomes

Pain intensity (NRS). Analgesic consumption. Pain outcomes reported at 1, 6, 12, 24, 36 and 48 h postoperatively. AEs

Surgery type

Arthroscopic shoulder surgery

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

42.9 ± 19

50 ± 14.1

Notes

No mention of sponsorship or funding. The study authors declare no conflicts of interest

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation by a computer‐generated random number table

Allocation concealment (selection bias)

Unclear risk

Only said that an anaesthetist blinded to group assignments prepared study drugs but no further description of allocation concealment

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

All predefined outcomes reported

Size

High risk

20 participants per treatment arm
Wu 2009

Study characteristics

Methods

Randomised, double‐blind

Participants

N = 30, about 27% women

Interventions

Perioperative ketamine infusion 0.08 mg/kg/h IV with morphine for 50 h vs morphine alone

Outcomes

Pain intensity (VAS) reported at 4, 8, 20 and 24 h postoperatively. Analgesic consumption at 0‐8 h, 8‐24 h, 24‐48 h after surgery (median values). Cumulative analgesic consumption at 48 h postoperatively. AEs

Surgery type

Elective radical operation for oesophageal carcinoma

Group numbers after end of study (treatment/control)

15/15

Age of patient population (treatment/control)

56 ± 11

58 ± 10

Notes

Article in Chinese. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Mentioned "double blind" but blinding not described in detail

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Mentioned "double blind" but blinding not described in detail

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No withdrawals

Selective reporting (reporting bias)

High risk

Predefined observer's assessment of awareness/sedation scores not provided

Size

High risk

15 participants per treatment arm
Yalcin 2012

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 90, 100% women

Interventions

Ketamine 0.5 mg/kg bolus IV before anaesthesia induction + 5 µg/kg/min infusion IV until skin closure

Outcomes

Pain intensity (VAS). Analgesic consumption. AEs

Main outcomes at 2, 4, 6, 12 and 24 hrs postoperatively

Surgery type

Total abdominal hysterectomy

Group numbers after end of study (treatment/control)

26/27

Age of patient population (treatment/control)

48.3 ± 5.7

48.1 ± 6

Notes

The 3rd group that received paracetamol as study drug was excluded from analysis

No financial or competing interests

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

A computer‐generated random number system

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded observer

Incomplete outcome data (attrition bias)
All outcomes

High risk

12% was withdrawn

Selective reporting (reporting bias)

Unclear risk

Exact numbers of AEs not reported

Size

High risk

26 and 27 participants per treatment arm
Yamauchi 2008

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 202, about 30% women

Interventions

  1. Ketamine 1 mg/kg bolus IV at skin incision + 42 µg/kg/h infusion IV for 24 h

  2. Ketamine 1 mg/kg bolus IV at skin incision + 83 µg/kg/h infusion IV for 24 h

Outcomes

Pain intensity (VAS) at rest and during movement at 1, 6, 12, 24, 36, 48 h and 3, 6 and 10 days after surgery. Analgesic consumption. AEs

Surgery type

Posterior cervical spine and lumbar spine surgery

Group numbers after end of study (treatment/control)

133/67

Age of patient population (treatment/control)

60.2 ± 16.9

57 ± 17.3

Notes

The study consists of cervical and lumbar surgery participants with 2 different interventions and corresponding control groups. These treatment arms (4 treatment arms and corresponding control groups) were analysed separately. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomisation by shuffling envelopes

Allocation concealment (selection bias)

Low risk

Allocation concealment in envelopes

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Mentioned "double‐blind" but not described

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Blinding not described

Incomplete outcome data (attrition bias)
All outcomes

Low risk

1% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

22, 23 and 23 participants in the cervical surgery groups. 42, 46 and 44 participants in the lumbar surgery groups

Yazigi 2012

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, about 52% women

Interventions

Pre‐incisional ketamine 0.1 mg/kg bolus IV + 0.05 mg/kg/h infusion IV during surgery and for 72 h postoperatively

Outcomes

Pain intensity (VAS) reported every 6 h for 3 days postoperatively. Cumulative analgesic requirement reported at 72 h. AEs

Surgery type

Thoracotomy

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

57.3 ± 11.9

56.9 ± 12.5

Notes

No financial support or funding and no conflict of interest

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Random number table

Allocation concealment (selection bias)

Low risk

Central allocation by the hospital pharmacy (a third party). Study drugs were prepared in identical containers and marked with the name of the study and a consecutive number

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

30 participants per treatment arm
Yeom 2012

Study characteristics

Methods

Randomised, double‐blind. Ketamine + fentanyl vs fentanyl

Participants

N = 40, 70% women

Interventions

Ketamine 0.2 mg/kg bolus IV + 30 µg/mL/kg infusion IV intraoperatively

Outcomes

Pain intensity (NRS). AEs. Ketamine and fentanyl infusion rates. Outcomes recorded at 1, 24 and 48 h after surgery

Surgery type

Lumbar spinal fusion

Group numbers after end of study (treatment/control)

20/20

Age of patient population (treatment/control)

61 ± 10

64.5 ± 11.5

Notes

No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described in detail.

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded personnel prepared study drugs

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel assessed outcomes

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

High risk

Not all AEs are reported that were predefined in methods

Size

High risk

20 participants per treatment arm
Ysasi 2010

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 60, about 30% women

Interventions

Ketamine infusion 8 µg/kg/min IV during surgery

Outcomes

Pain intensity (VAS, SVS) reported at 15 and 30 mins, then 1, 2, 4, 6, 8, 12 and 24 h postoperatively. Analgesic consumption reported at 24 h postoperatively. AEs

Surgery type

Myocardial revascularisation

Group numbers after end of study (treatment/control)

30/30

Age of patient population (treatment/control)

62.2 ± 10

63.3 ± 9.6

Notes

Article in Spanish. No mention of sponsorship or funding

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Randomisation process not described

Allocation concealment (selection bias)

Unclear risk

Allocation concealment method not described

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded participants and personnel

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded personnel

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No withdrawals

Selective reporting (reporting bias)

Low risk

Predefined outcomes reported

Size

High risk

30 participants per treatment arm
Zakine 2008

Study characteristics

Methods

Randomised, double‐blind, placebo control

Participants

N = 81, 23% women

Interventions

  1. Pre‐incisional ketamine 0.5 mg/kg bolus IV + 2 µg/kg/min infusion IV during surgery

  2. Pre‐incisional ketamine 0.5 mg/kg bolus IV + 2 µg/kg/min infusion IV during surgery and for 48 h postoperatively

Heterogeneous procedures

Outcomes

Pain intensity (VAS). Analgesic consumption. AEs. Pain outcomes recorded at 4, 24 and 48 h after surgery

Surgery type

Major abdominal, urologic or vascular surgery

Group numbers after end of study (treatment/control)

50/27

Age of patient population (treatment/control)

median (interquartile range)

63 (12)

62 (14)

Notes

Various procedures. Supported by a grant from the French Ministry of Health

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation

Allocation concealment (selection bias)

Low risk

Quote: "Patients were randomized by means of computer‐generated opaque envelopes containing the patient number and group assignment."

Blinding of participants and personnel (performance bias)
All outcomes

Unclear risk

Mentioned "double‐blind" but blinding not described in detail

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Mentioned "double‐blind" but blinding not described in detail

Incomplete outcome data (attrition bias)
All outcomes

Low risk

5% was withdrawn

Selective reporting (reporting bias)

Low risk

Predefined outcomes adequately reported

Size

High risk

27, 23 and 27 participants per treatment arm

AEs: adverse events;ED: epidural, ICDSC: intensive care delirium screening checklist, h: hour(s), ICU: intensive care unit, IV: intravenous, mcg: micrograms, mg: milligrams, min: minutes, kg: kilograms, N: number of participants, NPRS: numeric pain rating scale, NPSI: neuropathic pain symptom inventory, NRS: numerical rating scale, PACU: post‐anaesthesia care unit, PCA: patient‐controlled analgesia, PCEA: patient‐controlled epidural analgesia, PONV: post‐operative nausea and vomiting; PTPS: post‐thoracotomy pain syndrome; SC: subcutaneous; VAS: visual analogue scale, VNS: verbal numeric scale; VRS: verbal rating scale

Characteristics of excluded studies [ordered by study ID]

Ir a:

Study

Reason for exclusion

Abrishamkar 2012

Open‐label study

Adams 2003

Open‐label study

Aghamohammadi 2012

Inappropriate method ‐ study compared 3 different active treatment regimens, with no placebo

Akca 2016

Inappropriate method ‐ pain measured but not reported, except as a binary outcome at short postoperative time scales

Avidan 2017

Inappropriate method ‐ different anaesthesia techniques

Behdad 2011

Open‐label study

Bentley 2005

Inappropriate method ‐ number of participants in each study group was not reported

Bilgin 2005

Inappropriate method ‐ all participants treated with ketamine

Clausen 1975

Inappropriate pain scale (measurement)

Edwards 1993

Number of participants who completed the study fewer than 10

Gillies 2007

Inappropriate method ‐ mixed population of adults and children

Guan 2008

Number of participants who completed the study fewer than 10

Heinke 1999

Inappropriate method ‐ the primary outcome was PCA consumption of piritramide, but fixed maximum dose of piritramide limited the utility of the study to detect differences

Hong 2011

Open‐label study

Ito 1974

Open‐label study

Jahangir 1993

Inappropriate method ‐ time with study drug infusion varied, and so groups may not have been comparable in ketamine dose

Jensen 2008

Inappropriate method ‐ no general anaesthesia

Jiang 2016

Pain scores were not reported in any detail (measurement)

Joachimmson 1986

Inappropriate pain scale. Participants on ventilator and probably not able to communicate easily (measurement)

Kadic 2016

Inappropriate method ‐ participants in the same study group received ketamine and pregabalin so effects of ketamine could not be identified

Kim 2001

Inappropriate description of methods ‐ not described and may not be blinded

Kim 2005

Open‐label study

Kollender 2008

Open‐label study

Kose 2008

No pain or analgesic consumption outcome reported (measurement)

Launo 2004

Inappropriate method ‐ ketamine was compared to tramadol with no placebo

Lee 2005

Open‐label study

Lee 2006

Inappropriate description of methods ‐ not described and may not be blinded

Lee 2013

Open‐label study

Lee 2014

Open‐label study

Liang 2006

Inappropriate description of methods ‐ not described and may not be blinded

Lux 2009

Inappropriate randomisation ‐ participants divided sequentially into 2 groups

Malek 2006

Inappropriate method ‐ outcome is chronic pain

Maurset 1989

Number of participants who completed the study fewer than 10

Nayar 2009

Open‐label study

Ndoye 2008

Not an RCT

Nesher 2008

Inappropriate randomisation. Participants assigned to 1 of 2 groups according to their national ID‐number

Nesher 2009

Inappropriate randomisation. Randomisation according to the national ID‐number

Nikolayev 2008

Open‐label study

Nitta 2013

Open‐label study

Nourozi 2010

Inappropriate method ‐ mixed population of adults and children

Oliveira 2005

Inappropriate method ‐ all participants treated with ketamine

Owen 1987

Inappropriate method ‐ not placebo‐controlled

Park 2004

Methods not described and may not be blinded

Perrin 2009

Number of participants in group who completed the study fewer than 10

Reeves 2001

Inappropriate method ‐ different PCA settings for different participants, so non‐standardised treatment regimens

Sadove 1971

Inappropriate method ‐ not IV ketamine administration

Sollazzi 2008

Open‐label study

Song 2004

Methods not described and may not be blinded

Sveticic 2008

Inappropriate method ‐ different anaesthesia techniques (general anaesthesia, regional anaesthesia or combined)

Talu 2002

Inappropriate method ‐ not IV

Thomas 2012

Open‐label study

Tverskoy 1994

Number of participants in group who completed the study fewer than 10

Tverskoy 1996

Number of participants in group who completed the study fewer than 10

Ünlügenc 2002

Inappropriate method ‐ different PCA settings for different participants

Urban 2008

Open‐label study

Weinbroum 2003

Inappropriate randomisation ‐ participants allocated into 1 of the 2 treatment protocols on alternate days

Wilder‐Smith 1998

Inappropriate method ‐ study compared 3 different treatment regimens without a placebo comparator group

Xie 2003

Inappropriate method ‐ placebo administered epidurally, so no comparison group for IV ketamine

Xu 2017

Inappropriate method ‐ no general anaesthesia

ID‐number: identification number, IV: intravenous; PCA: patient‐controlled analgesia; RCT: randomised controlled trial

Characteristics of studies awaiting classification [ordered by study ID]

Ir a:

Lee 2018

Methods

A prospective, randomised, double‐blind, placebo‐controlled study

Participants

N = 64, robotic thyroidectomy

Interventions

Pre‐incisional ketamine 0.15 mg/kg IV followed by a continuous infusion 2 mcg/kg/min until the end of procedure

Outcomes

Primary endpoint: pain intensity (VAS) at 6 h postoperatively. Secondary outcomes: pain intensity (VAS) at 0, 1, 24 and 48 h and at 3 months postoperatively at rest and while coughing. Incidence of hypoesthesia, time administration of the first analgesic, number of participants requiring additional analgesics, complications related to opioids or ketamine

Notes

Results for pain outcomes are provided as median (IQR) thus cannot be used in meta‐analysis. AEs are reported as N (%)

Lou 2017

Methods

Prospective, randomised study

Participants

N = 66. Mastectomy

Interventions

Ketamine 0.5 mg/kg infused in 1 h daily for 7 days vs saline (NaCl 0.9%)

Outcomes

Postoperative pain (VAS) during PACU, 4 h, 24 h and 2‐5 days after surgery. Analgesic requirement at same time points. Hospital Anxiety and Depression Scale (HADS) 5 days after surgery. Incidence of postmastectomy pain syndrome, pain site and HADS at 3 and 6 months after surgery

Notes

Original article is in Chinese. Only abstract available
Moon 2018

Methods

Not known.

Participants

N = 46. Laparoscopic hysterectomy

Interventions

Pre‐incisional ketamine 1 mg/kg IV followed by a continuous infusion 0.5 mg/kg/h vs saline (NaCl 0.9%)

Outcomes

Primary outcome: mechanical pain threshold evaluating hyperalgesia.

Secondary outcomes: postoperative pain (VAS). Analgesic and antiemetic consumption. Incidence of dizziness

Notes

Only abstract available

AEs: adverse events; IQR: interquartile range,h: hour/s, IV: intravenous, kg: kilograms, mcg: micrograms, mg: milligrams, min: minutes, N: number of participants, PACU: post‐anaesthesia care unit; VAS: visual analogue scale

Data and analyses

Open in table viewer
Comparison 1. Perioperative ketamine versus control in a non‐stratified study population

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Opioid consumption at 24 hours Show forest plot

65

4004

Mean Difference (IV, Random, 95% CI)

‐7.63 [‐8.88, ‐6.39]
Analysis 1.1
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours

1.2 Opioid consumption at 48 hours Show forest plot

37

2449

Mean Difference (IV, Random, 95% CI)

‐12.62 [‐15.06, ‐10.18]
Analysis 1.2
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours

1.3 Pain intensity at rest at 24 hours Show forest plot

82

5004

Mean Difference (IV, Random, 95% CI)

‐5.09 [‐6.55, ‐3.64]
Analysis 1.3
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours

1.4 Pain intensity during movement at 24 hours Show forest plot

29

1806

Mean Difference (IV, Random, 95% CI)

‐5.60 [‐10.72, ‐0.48]
Analysis 1.4
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours

1.5 Pain intensity at rest at 48 hours Show forest plot

49

2962

Mean Difference (IV, Random, 95% CI)

‐5.03 [‐6.65, ‐3.40]
Analysis 1.5
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours

1.6 Pain intensity during movement at 48 hours Show forest plot

23

1353

Mean Difference (IV, Random, 95% CI)

‐5.72 [‐10.15, ‐1.29]
Analysis 1.6
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours

1.7 Time to first request for analgesia/trigger of PCA Show forest plot

31

1678

Mean Difference (IV, Random, 95% CI)

53.89 [37.00, 70.78]
Analysis 1.7
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 7: Time to first request for analgesia/trigger of PCA

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 7: Time to first request for analgesia/trigger of PCA

1.8 CNS adverse events ‐ all studies Show forest plot

105

6538

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.95, 1.43]
Analysis 1.8
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 8: CNS adverse events ‐ all studies

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 8: CNS adverse events ‐ all studies

1.9 Hyperalgesia Show forest plot

7

333

Mean Difference (IV, Random, 95% CI)

‐7.08 [‐11.92, ‐2.23]
Analysis 1.9
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 9: Hyperalgesia

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 9: Hyperalgesia

1.10 CNS adverse events ‐ studies with events Show forest plot

52

3706

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.95, 1.43]
Analysis 1.10
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 10: CNS adverse events ‐ studies with events

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 10: CNS adverse events ‐ studies with events

1.11 Postoperative nausea and vomiting ‐ all studies Show forest plot

95

5965

Risk Ratio (M‐H, Random, 95% CI)

0.88 [0.81, 0.96]
Analysis 1.11
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 11: Postoperative nausea and vomiting ‐ all studies

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 11: Postoperative nausea and vomiting ‐ all studies

Open in table viewer
Comparison 2. Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Opioid consumption at 24 hours Show forest plot

28

1639

Mean Difference (IV, Random, 95% CI)

‐6.26 [‐8.42, ‐4.11]
Analysis 2.1
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 1: Opioid consumption at 24 hours

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 1: Opioid consumption at 24 hours

2.1.1 Pre‐incisional ketamine

19

1045

Mean Difference (IV, Random, 95% CI)

‐5.54 [‐7.95, ‐3.12]

2.1.2 Postoperative ketamine

9

594

Mean Difference (IV, Random, 95% CI)

‐8.66 [‐13.84, ‐3.49]

2.2 Opioid consumption at 48 hours Show forest plot

16

959

Mean Difference (IV, Random, 95% CI)

‐10.76 [‐14.84, ‐6.68]
Analysis 2.2
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 2: Opioid consumption at 48 hours

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 2: Opioid consumption at 48 hours

2.2.1 Pre‐incisional ketamine

9

534

Mean Difference (IV, Random, 95% CI)

‐3.88 [‐7.04, ‐0.72]

2.2.2 Postoperative ketamine

7

425

Mean Difference (IV, Random, 95% CI)

‐20.81 [‐27.39, ‐14.24]

2.3 Pain intensity at 24 hours Show forest plot

29

1646

Mean Difference (IV, Random, 95% CI)

‐7.08 [‐9.56, ‐4.59]
Analysis 2.3
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 3: Pain intensity at 24 hours

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 3: Pain intensity at 24 hours

2.3.1 Pre‐incisional ketamine

20

1075

Mean Difference (IV, Random, 95% CI)

‐6.65 [‐10.06, ‐3.24]

2.3.2 Postoperative ketamine

9

571

Mean Difference (IV, Random, 95% CI)

‐8.30 [‐12.55, ‐4.05]

2.4 Pain intensity at 48 hours Show forest plot

15

840

Mean Difference (IV, Random, 95% CI)

‐5.49 [‐7.72, ‐3.25]
Analysis 2.4
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 4: Pain intensity at 48 hours

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 4: Pain intensity at 48 hours

2.4.1 Pre‐incisional ketamine

9

509

Mean Difference (IV, Random, 95% CI)

‐4.36 [‐7.53, ‐1.19]

2.4.2 Postoperative ketamine

6

331

Mean Difference (IV, Random, 95% CI)

‐8.02 [‐15.79, ‐0.26]

2.5 Time to first request for analgesia/first trigger of PCA Show forest plot

13

643

Mean Difference (IV, Random, 95% CI)

37.70 [20.87, 54.52]
Analysis 2.5
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 5: Time to first request for analgesia/first trigger of PCA

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 5: Time to first request for analgesia/first trigger of PCA

Open in table viewer
Comparison 3. Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Opioid consumption at 24 hours Show forest plot

33

2176

Mean Difference (IV, Random, 95% CI)

‐7.31 [‐9.78, ‐4.84]
Analysis 3.1
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours

3.2 Opioid consumption at 48 hours Show forest plot

15

1110

Mean Difference (IV, Random, 95% CI)

‐14.78 [‐21.12, ‐8.44]
Analysis 3.2
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours

3.3 Pain intensity at rest at 24 hours Show forest plot

32

2053

Mean Difference (IV, Random, 95% CI)

‐8.13 [‐10.84, ‐5.42]
Analysis 3.3
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours

3.4 Pain intensity during movement at 24 hours Show forest plot

10

613

Mean Difference (IV, Random, 95% CI)

‐6.50 [‐18.97, 5.97]
Analysis 3.4
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours

3.5 Pain intensity at rest at 48 hours Show forest plot

18

1202

Mean Difference (IV, Random, 95% CI)

‐6.38 [‐9.91, ‐2.84]
Analysis 3.5
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours

3.6 Pain intensity during movement at 48 hours Show forest plot

8

523

Mean Difference (IV, Random, 95% CI)

‐4.47 [‐13.08, 4.14]
Analysis 3.6
Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours

Open in table viewer
Comparison 4. CNS adverse events in studies with benzodiazepine premedication

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 CNS adverse events Show forest plot

65

3943

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.86, 1.38]
Analysis 4.1
Comparison 4: CNS adverse events in studies with benzodiazepine premedication, Outcome 1: CNS adverse events

Comparison 4: CNS adverse events in studies with benzodiazepine premedication, Outcome 1: CNS adverse events

Open in table viewer
Comparison 5. Perioperative ketamine versus control: thoracotomy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

5.1 Opioid consumption at 24 hours Show forest plot

4

241

Mean Difference (IV, Random, 95% CI)

‐5.81 [‐10.28, ‐1.35]
Analysis 5.1
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 1: Opioid consumption at 24 hours

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 1: Opioid consumption at 24 hours

5.2 Opioid consumption at 48 hours Show forest plot

3

191

Mean Difference (IV, Random, 95% CI)

‐12.52 [‐18.34, ‐6.71]
Analysis 5.2
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 2: Opioid consumption at 48 hours

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 2: Opioid consumption at 48 hours

5.3 Pain intensity at rest at 24 hours Show forest plot

13

782

Mean Difference (IV, Random, 95% CI)

‐3.90 [‐8.80, 1.00]
Analysis 5.3
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 3: Pain intensity at rest at 24 hours

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 3: Pain intensity at rest at 24 hours

5.4 Pain intensity during movement at 24 hours Show forest plot

5

315

Mean Difference (IV, Random, 95% CI)

‐7.32 [‐20.10, 5.45]
Analysis 5.4
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 4: Pain intensity during movement at 24 hours

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 4: Pain intensity during movement at 24 hours

5.5 Pain intensity at rest at 48 hours Show forest plot

9

530

Mean Difference (IV, Random, 95% CI)

‐6.86 [‐10.37, ‐3.35]
Analysis 5.5
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 5: Pain intensity at rest at 48 hours

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 5: Pain intensity at rest at 48 hours

5.6 Pain intensity during movement at 48 hours Show forest plot

5

298

Mean Difference (IV, Random, 95% CI)

‐10.64 [‐15.27, ‐6.00]
Analysis 5.6
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 6: Pain intensity during movement at 48 hours

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 6: Pain intensity during movement at 48 hours

Open in table viewer
Comparison 6. Perioperative ketamine versus control: major orthopaedic surgery

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

6.1 Opioid consumption at 24 hours Show forest plot

10

797

Mean Difference (IV, Random, 95% CI)

‐19.68 [‐28.55, ‐10.82]
Analysis 6.1
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 1: Opioid consumption at 24 hours

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 1: Opioid consumption at 24 hours

6.2 Opioid consumption at 48 hours Show forest plot

9

557

Mean Difference (IV, Random, 95% CI)

‐18.69 [‐27.47, ‐9.90]
Analysis 6.2
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 2: Opioid consumption at 48 hours

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 2: Opioid consumption at 48 hours

6.3 Pain intensity at rest at 24 hours Show forest plot

11

843

Mean Difference (IV, Random, 95% CI)

‐6.45 [‐9.86, ‐3.03]
Analysis 6.3
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 3: Pain intensity at rest at 24 hours

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 3: Pain intensity at rest at 24 hours

6.4 Pain intensity during movement at 24 hours Show forest plot

4

279

Mean Difference (IV, Random, 95% CI)

‐6.73 [‐12.64, ‐0.82]
Analysis 6.4
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 4: Pain intensity during movement at 24 hours

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 4: Pain intensity during movement at 24 hours

6.5 Pain intensity at rest at 48 hours Show forest plot

7

453

Mean Difference (IV, Random, 95% CI)

‐1.39 [‐4.10, 1.32]
Analysis 6.5
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 5: Pain intensity at rest at 48 hours

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 5: Pain intensity at rest at 48 hours

6.6 Pain intensity during movement at 48 hours Show forest plot

4

157

Mean Difference (IV, Random, 95% CI)

‐7.36 [‐13.12, ‐1.60]
Analysis 6.6
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 6: Pain intensity during movement at 48 hours

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 6: Pain intensity during movement at 48 hours

Open in table viewer
Comparison 7. Perioperative ketamine versus control: major abdominal surgery

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

7.1 Opioid consumption at 24 hours Show forest plot

16

1029

Mean Difference (IV, Random, 95% CI)

‐10.26 [‐13.75, ‐6.76]
Analysis 7.1
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 1: Opioid consumption at 24 hours

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 1: Opioid consumption at 24 hours

7.2 Opioid consumption at 48 hours Show forest plot

10

704

Mean Difference (IV, Random, 95% CI)

‐14.34 [‐21.21, ‐7.48]
Analysis 7.2
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 2: Opioid consumption at 48 hours

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 2: Opioid consumption at 48 hours

7.3 Pain intensity at rest at 24 hours Show forest plot

18

1178

Mean Difference (IV, Random, 95% CI)

‐7.42 [‐10.63, ‐4.21]
Analysis 7.3
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 3: Pain intensity at rest at 24 hours

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 3: Pain intensity at rest at 24 hours

7.4 Pain intensity during movement at 24 hours Show forest plot

9

666

Mean Difference (IV, Random, 95% CI)

‐2.80 [‐11.24, 5.65]
Analysis 7.4
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 4: Pain intensity during movement at 24 hours

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 4: Pain intensity during movement at 24 hours

7.5 Pain intensity at rest at 48 hours Show forest plot

13

891

Mean Difference (IV, Random, 95% CI)

‐5.99 [‐8.89, ‐3.08]
Analysis 7.5
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 5: Pain intensity at rest at 48 hours

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 5: Pain intensity at rest at 48 hours

7.6 Pain intensity during movement at 48 hours Show forest plot

9

662

Mean Difference (IV, Random, 95% CI)

‐2.91 [‐9.15, 3.34]
Analysis 7.6
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 6: Pain intensity during movement at 48 hours

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 6: Pain intensity during movement at 48 hours

Open in table viewer
Comparison 8. Perioperative ketamine versus control: total abdominal hysterectomy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

8.1 Opioid consumption at 24 hours Show forest plot

9

511

Mean Difference (IV, Random, 95% CI)

‐5.18 [‐10.77, 0.41]
Analysis 8.1
Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 1: Opioid consumption at 24 hours

Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 1: Opioid consumption at 24 hours

8.2 Opioid consumption at 48 hours Show forest plot

5

378

Mean Difference (IV, Random, 95% CI)

‐15.32 [‐33.20, 2.56]
Analysis 8.2
Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 2: Opioid consumption at 48 hours

Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 2: Opioid consumption at 48 hours

8.3 Pain intensity at rest at 24 hours Show forest plot

8

493

Mean Difference (IV, Random, 95% CI)

‐2.58 [‐4.64, ‐0.52]
Analysis 8.3
Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 3: Pain intensity at rest at 24 hours

Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 3: Pain intensity at rest at 24 hours

Open in table viewer
Comparison 9. Perioperative ketamine versus control: laparoscopic procedures

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

9.1 Opioid consumption at 24 hours Show forest plot

4

199

Mean Difference (IV, Random, 95% CI)

‐2.67 [‐6.19, 0.84]
Analysis 9.1
Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 1: Opioid consumption at 24 hours

Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 1: Opioid consumption at 24 hours

9.2 Opioid consumption at 48 hours Show forest plot

2

85

Mean Difference (IV, Random, 95% CI)

‐4.47 [‐12.21, 3.27]
Analysis 9.2
Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 2: Opioid consumption at 48 hours

Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 2: Opioid consumption at 48 hours

9.3 Pain intensity at rest at 24 hours Show forest plot

9

484

Mean Difference (IV, Random, 95% CI)

‐2.32 [‐6.65, 2.02]
Analysis 9.3
Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 3: Pain intensity at rest at 24 hours

Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 3: Pain intensity at rest at 24 hours

Study flow diagram

Figuras y tablas -
Figure 1

Study flow diagram

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'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

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'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

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours

Figuras y tablas -
Analysis 1.1

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours

Figuras y tablas -
Analysis 1.2

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours

Figuras y tablas -
Analysis 1.3

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours

Figuras y tablas -
Analysis 1.4

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours

Figuras y tablas -
Analysis 1.5

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours

Figuras y tablas -
Analysis 1.6

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 7: Time to first request for analgesia/trigger of PCA

Figuras y tablas -
Analysis 1.7

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 7: Time to first request for analgesia/trigger of PCA

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 8: CNS adverse events ‐ all studies

Figuras y tablas -
Analysis 1.8

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 8: CNS adverse events ‐ all studies

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 9: Hyperalgesia

Figuras y tablas -
Analysis 1.9

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 9: Hyperalgesia

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 10: CNS adverse events ‐ studies with events

Figuras y tablas -
Analysis 1.10

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 10: CNS adverse events ‐ studies with events

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Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 11: Postoperative nausea and vomiting ‐ all studies

Figuras y tablas -
Analysis 1.11

Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 11: Postoperative nausea and vomiting ‐ all studies

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Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 1: Opioid consumption at 24 hours

Figuras y tablas -
Analysis 2.1

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 1: Opioid consumption at 24 hours

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Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 2: Opioid consumption at 48 hours

Figuras y tablas -
Analysis 2.2

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 2: Opioid consumption at 48 hours

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Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 3: Pain intensity at 24 hours

Figuras y tablas -
Analysis 2.3

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 3: Pain intensity at 24 hours

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Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 4: Pain intensity at 48 hours

Figuras y tablas -
Analysis 2.4

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 4: Pain intensity at 48 hours

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Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 5: Time to first request for analgesia/first trigger of PCA

Figuras y tablas -
Analysis 2.5

Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 5: Time to first request for analgesia/first trigger of PCA

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Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours

Figuras y tablas -
Analysis 3.1

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours

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Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours

Figuras y tablas -
Analysis 3.2

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours

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Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours

Figuras y tablas -
Analysis 3.3

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours

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Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours

Figuras y tablas -
Analysis 3.4

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours

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Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours

Figuras y tablas -
Analysis 3.5

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours

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Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours

Figuras y tablas -
Analysis 3.6

Comparison 3: Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours

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Comparison 4: CNS adverse events in studies with benzodiazepine premedication, Outcome 1: CNS adverse events

Figuras y tablas -
Analysis 4.1

Comparison 4: CNS adverse events in studies with benzodiazepine premedication, Outcome 1: CNS adverse events

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Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 1: Opioid consumption at 24 hours

Figuras y tablas -
Analysis 5.1

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 1: Opioid consumption at 24 hours

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Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 2: Opioid consumption at 48 hours

Figuras y tablas -
Analysis 5.2

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 2: Opioid consumption at 48 hours

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Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 3: Pain intensity at rest at 24 hours

Figuras y tablas -
Analysis 5.3

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 3: Pain intensity at rest at 24 hours

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Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 4: Pain intensity during movement at 24 hours

Figuras y tablas -
Analysis 5.4

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 4: Pain intensity during movement at 24 hours

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Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 5: Pain intensity at rest at 48 hours

Figuras y tablas -
Analysis 5.5

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 5: Pain intensity at rest at 48 hours

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Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 6: Pain intensity during movement at 48 hours

Figuras y tablas -
Analysis 5.6

Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 6: Pain intensity during movement at 48 hours

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Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 1: Opioid consumption at 24 hours

Figuras y tablas -
Analysis 6.1

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 1: Opioid consumption at 24 hours

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Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 2: Opioid consumption at 48 hours

Figuras y tablas -
Analysis 6.2

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 2: Opioid consumption at 48 hours

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Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 3: Pain intensity at rest at 24 hours

Figuras y tablas -
Analysis 6.3

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 3: Pain intensity at rest at 24 hours

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Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 4: Pain intensity during movement at 24 hours

Figuras y tablas -
Analysis 6.4

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 4: Pain intensity during movement at 24 hours

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Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 5: Pain intensity at rest at 48 hours

Figuras y tablas -
Analysis 6.5

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 5: Pain intensity at rest at 48 hours

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Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 6: Pain intensity during movement at 48 hours

Figuras y tablas -
Analysis 6.6

Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 6: Pain intensity during movement at 48 hours

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Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 1: Opioid consumption at 24 hours

Figuras y tablas -
Analysis 7.1

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 1: Opioid consumption at 24 hours

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Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 2: Opioid consumption at 48 hours

Figuras y tablas -
Analysis 7.2

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 2: Opioid consumption at 48 hours

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Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 3: Pain intensity at rest at 24 hours

Figuras y tablas -
Analysis 7.3

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 3: Pain intensity at rest at 24 hours

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Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 4: Pain intensity during movement at 24 hours

Figuras y tablas -
Analysis 7.4

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 4: Pain intensity during movement at 24 hours

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Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 5: Pain intensity at rest at 48 hours

Figuras y tablas -
Analysis 7.5

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 5: Pain intensity at rest at 48 hours

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Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 6: Pain intensity during movement at 48 hours

Figuras y tablas -
Analysis 7.6

Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 6: Pain intensity during movement at 48 hours

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Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 1: Opioid consumption at 24 hours

Figuras y tablas -
Analysis 8.1

Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 1: Opioid consumption at 24 hours

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Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 2: Opioid consumption at 48 hours

Figuras y tablas -
Analysis 8.2

Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 2: Opioid consumption at 48 hours

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Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 3: Pain intensity at rest at 24 hours

Figuras y tablas -
Analysis 8.3

Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 3: Pain intensity at rest at 24 hours

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Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 1: Opioid consumption at 24 hours

Figuras y tablas -
Analysis 9.1

Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 1: Opioid consumption at 24 hours

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Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 2: Opioid consumption at 48 hours

Figuras y tablas -
Analysis 9.2

Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 2: Opioid consumption at 48 hours

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Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 3: Pain intensity at rest at 24 hours

Figuras y tablas -
Analysis 9.3

Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 3: Pain intensity at rest at 24 hours

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Summary of findings 1. Perioperative intravenous ketamine compared to placebo for acute postoperative pain in adults

Perioperative intravenous ketamine compared to placebo for acute postoperative pain: non‐stratified analysis

Patient or population: adults undergoing any type of surgery

Settings: immediate postoperative period

Intervention: intravenous ketamine given before, during, or after surgery

Comparison: intravenous placebo

Outcomes

Details

Number of participants
(studies)

Absolute values and effect of ketamine

Quality of the evidence
(GRADE)

Measured values with placebo

Difference with perioperative intravenous ketamine
(95% CI)

Opioid consumption
(mg morphine equivalents)

24 hours

4004
(65 RCTs)

Median 31 mg

(mean 42 mg)

MD 7.6 mg lower
(8.9 lower to 6.4 lower)

Moderate1

48 hours

2449
(37 RCTs)

Median 59 mg

(mean 67 mg)

MD 12.6 mg lower
(15 lower to 10 lower)

Moderate1

Pain intensity
(0‐100 mm VAS. 7

At rest 24 hours

5004
(82 RCTs)

Median 25 mm

(mean 26 mm)

MD 5 mm (VAS) lower
(6.6 lower to 3.6 lower)

High2

On movement 24 hours

1806
(29 RCTs)

Median 43 mm

(mean 42 mm)

MD 6 mm (VAS) lower
(11 lower to 0.5 lower)

Moderate1

At rest 48 hours

2962
(49 RCTs)

Median 21 mm

(mean 23 mm)

MD 5 mm (VAS) lower
(6.7 lower to 3.4 lower)

High2

On movement 48 hours

1353
(23 RCTs)

Median 37 mm

(mean 37 mm)

MD 6 mm (VAS) lower
(10 lower to 1.3 lower)

Low3

Time to first request for analgesia/trigger of PCA
(minutes)

All data (plus analysis omitting 1 highly aberrant study reporting time of over 1000 minutes)

1678
(31 RCTs)

Median 18 minutes

(mean 39 minutes)

MD 54 minutes longer
(37 to 71 longer)

(MD 22 minutes longer omitting aberrant study

(15 to 29 longer))

Moderate4

Hyperalgesia
(cm2)

As described, any time point

333
(7 RCTs)

Mean 15 cm2

MD 7 cm2 less
(12 to 2 less)

Very low5

CNS adverse events

All events (major and minor), as described, any time point

6538
(105 RCTs)

52 per 1000

42 per 1000

RR 1.2 (0.95 to 1.4)

High6

Postoperative nausea and vomiting

All studies reporting outcomes, as described, any time point

5965
(95 RCTs)

271 per 1000

230 per 1000

RR 0.88 (0.81 to 0.96

Need to treat 24 people to prevent one episode of PONV (16 to 54)

High6

CI: confidence interval; CNS: central nervous system; MD: mean difference; PCA: patient controlled analgesia; PONV: postoperative nausea and vomiting; RCT: randomised controlled trial; RR: risk ratio; VAS: visual analogue scale

GRADE Working Group grades of evidence
High quality: we are very confident that the true effect lies close to that of the estimate of the effect
Moderate quality: we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different
Low quality: our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect
Very low quality: we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect

1 Downgraded once for small study effect.
2 Not downgraded for small study effect because no reduction in effect with larger studies.
3 Downgraded once for small study effect, and once because fewer than 1500 participants.
4 Downgraded once because all studies small, more than 1500 participants but not possible to test for small‐study effects.
5 Downgraded three times because fewer than 400 participants.
6 Not downgraded: consistent across large body of data.
7 Lower VAS means less pain.

Figuras y tablas -
Summary of findings 1. Perioperative intravenous ketamine compared to placebo for acute postoperative pain in adults
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Comparison 1. Perioperative ketamine versus control in a non‐stratified study population

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1.1 Opioid consumption at 24 hours Show forest plot

65

4004

Mean Difference (IV, Random, 95% CI)

‐7.63 [‐8.88, ‐6.39]

1.2 Opioid consumption at 48 hours Show forest plot

37

2449

Mean Difference (IV, Random, 95% CI)

‐12.62 [‐15.06, ‐10.18]

1.3 Pain intensity at rest at 24 hours Show forest plot

82

5004

Mean Difference (IV, Random, 95% CI)

‐5.09 [‐6.55, ‐3.64]

1.4 Pain intensity during movement at 24 hours Show forest plot

29

1806

Mean Difference (IV, Random, 95% CI)

‐5.60 [‐10.72, ‐0.48]

1.5 Pain intensity at rest at 48 hours Show forest plot

49

2962

Mean Difference (IV, Random, 95% CI)

‐5.03 [‐6.65, ‐3.40]

1.6 Pain intensity during movement at 48 hours Show forest plot

23

1353

Mean Difference (IV, Random, 95% CI)

‐5.72 [‐10.15, ‐1.29]

1.7 Time to first request for analgesia/trigger of PCA Show forest plot

31

1678

Mean Difference (IV, Random, 95% CI)

53.89 [37.00, 70.78]

1.8 CNS adverse events ‐ all studies Show forest plot

105

6538

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.95, 1.43]

1.9 Hyperalgesia Show forest plot

7

333

Mean Difference (IV, Random, 95% CI)

‐7.08 [‐11.92, ‐2.23]

1.10 CNS adverse events ‐ studies with events Show forest plot

52

3706

Risk Ratio (M‐H, Random, 95% CI)

1.17 [0.95, 1.43]

1.11 Postoperative nausea and vomiting ‐ all studies Show forest plot

95

5965

Risk Ratio (M‐H, Random, 95% CI)

0.88 [0.81, 0.96]
Figuras y tablas -
Comparison 1. Perioperative ketamine versus control in a non‐stratified study population
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Comparison 2. Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

2.1 Opioid consumption at 24 hours Show forest plot

28

1639

Mean Difference (IV, Random, 95% CI)

‐6.26 [‐8.42, ‐4.11]

2.1.1 Pre‐incisional ketamine

19

1045

Mean Difference (IV, Random, 95% CI)

‐5.54 [‐7.95, ‐3.12]

2.1.2 Postoperative ketamine

9

594

Mean Difference (IV, Random, 95% CI)

‐8.66 [‐13.84, ‐3.49]

2.2 Opioid consumption at 48 hours Show forest plot

16

959

Mean Difference (IV, Random, 95% CI)

‐10.76 [‐14.84, ‐6.68]

2.2.1 Pre‐incisional ketamine

9

534

Mean Difference (IV, Random, 95% CI)

‐3.88 [‐7.04, ‐0.72]

2.2.2 Postoperative ketamine

7

425

Mean Difference (IV, Random, 95% CI)

‐20.81 [‐27.39, ‐14.24]

2.3 Pain intensity at 24 hours Show forest plot

29

1646

Mean Difference (IV, Random, 95% CI)

‐7.08 [‐9.56, ‐4.59]

2.3.1 Pre‐incisional ketamine

20

1075

Mean Difference (IV, Random, 95% CI)

‐6.65 [‐10.06, ‐3.24]

2.3.2 Postoperative ketamine

9

571

Mean Difference (IV, Random, 95% CI)

‐8.30 [‐12.55, ‐4.05]

2.4 Pain intensity at 48 hours Show forest plot

15

840

Mean Difference (IV, Random, 95% CI)

‐5.49 [‐7.72, ‐3.25]

2.4.1 Pre‐incisional ketamine

9

509

Mean Difference (IV, Random, 95% CI)

‐4.36 [‐7.53, ‐1.19]

2.4.2 Postoperative ketamine

6

331

Mean Difference (IV, Random, 95% CI)

‐8.02 [‐15.79, ‐0.26]

2.5 Time to first request for analgesia/first trigger of PCA Show forest plot

13

643

Mean Difference (IV, Random, 95% CI)

37.70 [20.87, 54.52]
Figuras y tablas -
Comparison 2. Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population
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Comparison 3. Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

3.1 Opioid consumption at 24 hours Show forest plot

33

2176

Mean Difference (IV, Random, 95% CI)

‐7.31 [‐9.78, ‐4.84]

3.2 Opioid consumption at 48 hours Show forest plot

15

1110

Mean Difference (IV, Random, 95% CI)

‐14.78 [‐21.12, ‐8.44]

3.3 Pain intensity at rest at 24 hours Show forest plot

32

2053

Mean Difference (IV, Random, 95% CI)

‐8.13 [‐10.84, ‐5.42]

3.4 Pain intensity during movement at 24 hours Show forest plot

10

613

Mean Difference (IV, Random, 95% CI)

‐6.50 [‐18.97, 5.97]

3.5 Pain intensity at rest at 48 hours Show forest plot

18

1202

Mean Difference (IV, Random, 95% CI)

‐6.38 [‐9.91, ‐2.84]

3.6 Pain intensity during movement at 48 hours Show forest plot

8

523

Mean Difference (IV, Random, 95% CI)

‐4.47 [‐13.08, 4.14]
Figuras y tablas -
Comparison 3. Perioperative ketamine versus control co‐administered with nitrous oxide in a non‐stratified study population
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Comparison 4. CNS adverse events in studies with benzodiazepine premedication

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

4.1 CNS adverse events Show forest plot

65

3943

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.86, 1.38]
Figuras y tablas -
Comparison 4. CNS adverse events in studies with benzodiazepine premedication
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Comparison 5. Perioperative ketamine versus control: thoracotomy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

5.1 Opioid consumption at 24 hours Show forest plot

4

241

Mean Difference (IV, Random, 95% CI)

‐5.81 [‐10.28, ‐1.35]

5.2 Opioid consumption at 48 hours Show forest plot

3

191

Mean Difference (IV, Random, 95% CI)

‐12.52 [‐18.34, ‐6.71]

5.3 Pain intensity at rest at 24 hours Show forest plot

13

782

Mean Difference (IV, Random, 95% CI)

‐3.90 [‐8.80, 1.00]

5.4 Pain intensity during movement at 24 hours Show forest plot

5

315

Mean Difference (IV, Random, 95% CI)

‐7.32 [‐20.10, 5.45]

5.5 Pain intensity at rest at 48 hours Show forest plot

9

530

Mean Difference (IV, Random, 95% CI)

‐6.86 [‐10.37, ‐3.35]

5.6 Pain intensity during movement at 48 hours Show forest plot

5

298

Mean Difference (IV, Random, 95% CI)

‐10.64 [‐15.27, ‐6.00]
Figuras y tablas -
Comparison 5. Perioperative ketamine versus control: thoracotomy
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Comparison 6. Perioperative ketamine versus control: major orthopaedic surgery

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

6.1 Opioid consumption at 24 hours Show forest plot

10

797

Mean Difference (IV, Random, 95% CI)

‐19.68 [‐28.55, ‐10.82]

6.2 Opioid consumption at 48 hours Show forest plot

9

557

Mean Difference (IV, Random, 95% CI)

‐18.69 [‐27.47, ‐9.90]

6.3 Pain intensity at rest at 24 hours Show forest plot

11

843

Mean Difference (IV, Random, 95% CI)

‐6.45 [‐9.86, ‐3.03]

6.4 Pain intensity during movement at 24 hours Show forest plot

4

279

Mean Difference (IV, Random, 95% CI)

‐6.73 [‐12.64, ‐0.82]

6.5 Pain intensity at rest at 48 hours Show forest plot

7

453

Mean Difference (IV, Random, 95% CI)

‐1.39 [‐4.10, 1.32]

6.6 Pain intensity during movement at 48 hours Show forest plot

4

157

Mean Difference (IV, Random, 95% CI)

‐7.36 [‐13.12, ‐1.60]
Figuras y tablas -
Comparison 6. Perioperative ketamine versus control: major orthopaedic surgery
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Comparison 7. Perioperative ketamine versus control: major abdominal surgery

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

7.1 Opioid consumption at 24 hours Show forest plot

16

1029

Mean Difference (IV, Random, 95% CI)

‐10.26 [‐13.75, ‐6.76]

7.2 Opioid consumption at 48 hours Show forest plot

10

704

Mean Difference (IV, Random, 95% CI)

‐14.34 [‐21.21, ‐7.48]

7.3 Pain intensity at rest at 24 hours Show forest plot

18

1178

Mean Difference (IV, Random, 95% CI)

‐7.42 [‐10.63, ‐4.21]

7.4 Pain intensity during movement at 24 hours Show forest plot

9

666

Mean Difference (IV, Random, 95% CI)

‐2.80 [‐11.24, 5.65]

7.5 Pain intensity at rest at 48 hours Show forest plot

13

891

Mean Difference (IV, Random, 95% CI)

‐5.99 [‐8.89, ‐3.08]

7.6 Pain intensity during movement at 48 hours Show forest plot

9

662

Mean Difference (IV, Random, 95% CI)

‐2.91 [‐9.15, 3.34]
Figuras y tablas -
Comparison 7. Perioperative ketamine versus control: major abdominal surgery
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Comparison 8. Perioperative ketamine versus control: total abdominal hysterectomy

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

8.1 Opioid consumption at 24 hours Show forest plot

9

511

Mean Difference (IV, Random, 95% CI)

‐5.18 [‐10.77, 0.41]

8.2 Opioid consumption at 48 hours Show forest plot

5

378

Mean Difference (IV, Random, 95% CI)

‐15.32 [‐33.20, 2.56]

8.3 Pain intensity at rest at 24 hours Show forest plot

8

493

Mean Difference (IV, Random, 95% CI)

‐2.58 [‐4.64, ‐0.52]
Figuras y tablas -
Comparison 8. Perioperative ketamine versus control: total abdominal hysterectomy
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Comparison 9. Perioperative ketamine versus control: laparoscopic procedures

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

9.1 Opioid consumption at 24 hours Show forest plot

4

199

Mean Difference (IV, Random, 95% CI)

‐2.67 [‐6.19, 0.84]

9.2 Opioid consumption at 48 hours Show forest plot

2

85

Mean Difference (IV, Random, 95% CI)

‐4.47 [‐12.21, 3.27]

9.3 Pain intensity at rest at 24 hours Show forest plot

9

484

Mean Difference (IV, Random, 95% CI)

‐2.32 [‐6.65, 2.02]
Figuras y tablas -
Comparison 9. Perioperative ketamine versus control: laparoscopic procedures
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