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Meta-Analysis
. 2018 Dec 20;12(12):CD012033.
doi: 10.1002/14651858.CD012033.pub4.

Perioperative intravenous ketamine for acute postoperative pain in adults

Elina Cv Brinck  1 , Elina Tiippana, Michael Heesen, Rae Frances Bell, Sebastian Straube, R Andrew Moore, Vesa Kontinen
Affiliations
Meta-Analysis

Perioperative intravenous ketamine for acute postoperative pain in adults

Elina Cv Brinck et al. Cochrane Database Syst Rev. .

Abstract

Background: Inadequate pain management after surgery increases the risk of postoperative complications and may predispose for chronic postsurgical pain. Perioperative ketamine may enhance conventional analgesics in the acute postoperative setting.

Objectives: To evaluate the efficacy and safety of perioperative intravenous ketamine in adult patients when used for the treatment or prevention of acute pain following general anaesthesia.

Search methods: We searched CENTRAL, MEDLINE and Embase to July 2018 and three trials registers (metaRegister of controlled trials, ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP)) together with reference checking, citation searching and contact with study authors to identify additional studies.

Selection criteria: We sought randomised, double-blind, controlled trials of adults undergoing surgery under general anaesthesia and being treated with perioperative intravenous ketamine. Studies compared ketamine with placebo, or compared ketamine plus a basic analgesic, such as morphine or non-steroidal anti-inflammatory drug (NSAID), with a basic analgesic alone.

Data collection and analysis: Two review authors searched for studies, extracted efficacy and adverse event data, examined issues of study quality and potential bias, and performed analyses. Primary outcomes were opioid consumption and pain intensity at rest and during movement at 24 and 48 hours postoperatively. Secondary outcomes were time to first analgesic request, assessment of postoperative hyperalgesia, central nervous system (CNS) adverse effects, and postoperative nausea and vomiting. We assessed the evidence using GRADE and created a 'Summary of findings' table.

Main results: We included 130 studies with 8341 participants. Ketamine was given to 4588 participants and 3753 participants served as controls. Types of surgery included ear, nose or throat surgery, wisdom tooth extraction, thoracotomy, lumbar fusion surgery, microdiscectomy, hip joint replacement surgery, knee joint replacement surgery, anterior cruciate ligament repair, knee arthroscopy, mastectomy, haemorrhoidectomy, abdominal surgery, radical prostatectomy, thyroid surgery, elective caesarean section, and laparoscopic surgery. Racemic ketamine bolus doses were predominantly 0.25 mg to 1 mg, and infusions 2 to 5 µg/kg/minute; 10 studies used only S-ketamine and one only R-ketamine. Risk of bias was generally low or uncertain, except for study size; most had fewer than 50 participants per treatment arm, resulting in high heterogeneity, as expected, for most analyses. We did not stratify the main analysis by type of surgery or any other factor, such as dose or timing of ketamine administration, and used a non-stratified analysis.Perioperative intravenous ketamine reduced postoperative opioid consumption over 24 hours by 8 mg morphine equivalents (95% CI 6 to 9; 19% from 42 mg consumed by participants given placebo, moderate-quality evidence; 65 studies, 4004 participants). Over 48 hours, opioid consumption was 13 mg lower (95% CI 10 to 15; 19% from 67 mg with placebo, moderate-quality evidence; 37 studies, 2449 participants).Perioperative intravenous ketamine reduced pain at rest at 24 hours by 5/100 mm on a visual analogue scale (95% CI 4 to 7; 19% lower from 26/100 mm with placebo, high-quality evidence; 82 studies, 5004 participants), and at 48 hours by 5/100 mm (95% CI 3 to 7; 22% lower from 23/100 mm, high-quality evidence; 49 studies, 2962 participants). Pain during movement was reduced at 24 hours (6/100 mm, 14% lower from 42/100 mm, moderate-quality evidence; 29 studies, 1806 participants), and 48 hours (6/100 mm, 16% lower from 37 mm, low-quality evidence; 23 studies, 1353 participants).Results for primary outcomes were consistent when analysed by pain at rest or on movement, operation type, and timing of administration, or sensitivity to study size and pain intensity. No analysis by dose was possible. There was no difference when nitrous oxide was used. We downgraded the quality of the evidence once if numbers of participants were large but small-study effects were present, or twice if numbers were small and small-study effects likely but testing not possible.Ketamine increased the time for the first postoperative analgesic request by 54 minutes (95% CI 37 to 71 minutes), from a mean of 39 minutes with placebo (moderate-quality evidence; 31 studies, 1678 participants). Ketamine reduced the area of postoperative hyperalgesia by 7 cm² (95% CI -11.9 to -2.2), compared with placebo (very low-quality evidence; 7 studies 333 participants). We downgraded the quality of evidence because of small-study effects or because the number of participants was below 400.CNS adverse events occurred in 52 studies, while 53 studies reported of absence of CNS adverse events. Overall, 187/3614 (5%) participants receiving ketamine and 122/2924 (4%) receiving control treatment experienced an adverse event (RR 1.2, 95% CI 0.95 to 1.4; high-quality evidence; 105 studies, 6538 participants). Ketamine reduced postoperative nausea and vomiting from 27% with placebo to 23% with ketamine (RR 0.88, 95% CI 0.81 to 0.96; the number needed to treat to prevent one episode of postoperative nausea and vomiting with perioperative intravenous ketamine administration was 24 (95% CI 16 to 54; high-quality evidence; 95 studies, 5965 participants).

Authors' conclusions: Perioperative intravenous ketamine probably reduces postoperative analgesic consumption and pain intensity. Results were consistent in different operation types or timing of ketamine administration, with larger and smaller studies, and by higher and lower pain intensity. CNS adverse events were little different with ketamine or control. Perioperative intravenous ketamine probably reduces postoperative nausea and vomiting by a small extent, of arguable clinical relevance.

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Conflict of interest statement

ECVB: none known. ECVB is a specialist physician in anaesthesiology and intensive care medicine and she treats patients suffering from acute postoperative pain.

ET: none known. ET is a specialist physician in anaesthesiology and intensive care medicine and she treats patients suffering from acute postoperative pain.

MH: none known. MH is a specialist physician in anaesthesiology and he treats patients with acute postoperative and chronic pain.

RFB: none known. RFB is a specialist pain physician (retired).

SS's institution (University of Alberta) received fees for his contribution to an advisory board from Daiichi Sankyo, Inc. (2015). SS is a specialist occupational medicine physician and some of the patients he assesses have painful conditions.

RAM has received grant support from Grünenthal relating to individual patient‐level analyses of trial data regarding tapentadol in osteoarthritis and back pain (2015), and Novartis for a network meta‐analysis on acute postoperative pain using data from Cochrane Reviews. He has received honoraria for attending boards with RB on understanding pharmacokinetics of drug uptake (2015). He has received honoraria from Omega Pharma (2016), and Futura Pharma (2016), for providing advice on trial and data analysis methods.

VK: none known. VK is a specialist physician in anaesthesiology and intensive care medicine and he treats patients suffering from acute postoperative pain.

Figures

1
1
Study flow diagram
2
2
'Risk of bias' graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
3
3
'Risk of bias' summary: review authors' judgements about each risk of bias item for each included study
1.1
1.1. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 1: Opioid consumption at 24 hours
1.2
1.2. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 2: Opioid consumption at 48 hours
1.3
1.3. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 3: Pain intensity at rest at 24 hours
1.4
1.4. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 4: Pain intensity during movement at 24 hours
1.5
1.5. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 5: Pain intensity at rest at 48 hours
1.6
1.6. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 6: Pain intensity during movement at 48 hours
1.7
1.7. Analysis
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
1.8. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 8: CNS adverse events ‐ all studies
1.9
1.9. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 9: Hyperalgesia
1.10
1.10. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 10: CNS adverse events ‐ studies with events
1.11
1.11. Analysis
Comparison 1: Perioperative ketamine versus control in a non‐stratified study population, Outcome 11: Postoperative nausea and vomiting ‐ all studies
2.1
2.1. Analysis
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 1: Opioid consumption at 24 hours
2.2
2.2. Analysis
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 2: Opioid consumption at 48 hours
2.3
2.3. Analysis
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 3: Pain intensity at 24 hours
2.4
2.4. Analysis
Comparison 2: Pre‐incisional and postoperative ketamine versus control in a non‐stratified patient population, Outcome 4: Pain intensity at 48 hours
2.5
2.5. Analysis
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
3.1
3.1. Analysis
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
3.2. Analysis
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
3.3. Analysis
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
3.4. Analysis
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
3.5. Analysis
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
3.6. Analysis
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
4.1
4.1. Analysis
Comparison 4: CNS adverse events in studies with benzodiazepine premedication, Outcome 1: CNS adverse events
5.1
5.1. Analysis
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 1: Opioid consumption at 24 hours
5.2
5.2. Analysis
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 2: Opioid consumption at 48 hours
5.3
5.3. Analysis
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 3: Pain intensity at rest at 24 hours
5.4
5.4. Analysis
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 4: Pain intensity during movement at 24 hours
5.5
5.5. Analysis
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 5: Pain intensity at rest at 48 hours
5.6
5.6. Analysis
Comparison 5: Perioperative ketamine versus control: thoracotomy, Outcome 6: Pain intensity during movement at 48 hours
6.1
6.1. Analysis
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 1: Opioid consumption at 24 hours
6.2
6.2. Analysis
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 2: Opioid consumption at 48 hours
6.3
6.3. Analysis
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 3: Pain intensity at rest at 24 hours
6.4
6.4. Analysis
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 4: Pain intensity during movement at 24 hours
6.5
6.5. Analysis
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 5: Pain intensity at rest at 48 hours
6.6
6.6. Analysis
Comparison 6: Perioperative ketamine versus control: major orthopaedic surgery, Outcome 6: Pain intensity during movement at 48 hours
7.1
7.1. Analysis
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 1: Opioid consumption at 24 hours
7.2
7.2. Analysis
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 2: Opioid consumption at 48 hours
7.3
7.3. Analysis
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 3: Pain intensity at rest at 24 hours
7.4
7.4. Analysis
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 4: Pain intensity during movement at 24 hours
7.5
7.5. Analysis
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 5: Pain intensity at rest at 48 hours
7.6
7.6. Analysis
Comparison 7: Perioperative ketamine versus control: major abdominal surgery, Outcome 6: Pain intensity during movement at 48 hours
8.1
8.1. Analysis
Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 1: Opioid consumption at 24 hours
8.2
8.2. Analysis
Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 2: Opioid consumption at 48 hours
8.3
8.3. Analysis
Comparison 8: Perioperative ketamine versus control: total abdominal hysterectomy, Outcome 3: Pain intensity at rest at 24 hours
9.1
9.1. Analysis
Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 1: Opioid consumption at 24 hours
9.2
9.2. Analysis
Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 2: Opioid consumption at 48 hours
9.3
9.3. Analysis
Comparison 9: Perioperative ketamine versus control: laparoscopic procedures, Outcome 3: Pain intensity at rest at 24 hours
See this image and copyright information in PMC

Comment in

References

References to studies included in this review

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Bilgen 2012 {published data only}
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Bornemann‐Cimenti 2016 {published data only}
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Burstal 2001 {published data only}
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Cenzig 2014 {published data only}
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Chen 2004 {published data only}
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Choi 2015 {published data only}
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Colombani 2008 {published data only}
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Crousier 2008 {published data only}
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Dal 2005 {published data only}
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Deng 2009 {published data only}
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Du 2011 {published data only}
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Dualé 2009 {published data only}
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Dullenkopf 2009 {published data only}
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Fiorelli 2015 {published data only}
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Galinski 2007 {published data only}
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Ganne 2005 {published data only}
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Garcia‐Navia 2016 {published data only}
    1. 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. [DOI: 10.7399/fh.2016.40.1.9339] - DOI - PubMed
Garg 2016 {published data only}
    1. 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. - PubMed
Gilabert Morell 2002 {published data only}
    1. 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. - PubMed
Grady 2012 {published data only}
    1. 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. [DOI: 10.1213/ANE0b013e3182662e01] - DOI - PubMed
Guignard 2002 {published data only}
    1. 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. [DOI: 10.1213/01.ANE.0000020699.65934.0F] - DOI - PubMed
Guillou 2003 {published data only}
    1. 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. [DOI: 10.1213/01.ANE.0000075837.67275.36] - DOI - PubMed
Hadi 2010 {published data only}
    1. 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. [DOI: 10.5414/CPP48542] - DOI - PubMed
Hadi 2013 {published data only}
    1. 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. [DOI: 10.1016/j.jsps.2012.08.002] - DOI - PMC - PubMed
Haliloglu 2015 {published data only}
    1. 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. [DOI: 10.3109/14767058.2015.1027190] - DOI - PubMed
Hasanein 2011 {published data only}
    1. 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. [DOI: 10.1016/j.egja.2011.07.009] - DOI
Hayes 2004 {published data only}
    1. 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. - PubMed
Helmy 2015 {published data only}
    1. 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. [DOI: 10.1016/j.egja.2014.12.006] - DOI
Hercock 1999 {published data only}
    1. 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.
Hu 2014 {published data only}
    1. 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. [DOI: 10.3109/15360288.2014.908992] - DOI - PubMed
Ilkjaer 1998 {published data only}
    1. 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. - PubMed
Jaksch 2002 {published data only}
    1. 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. - PubMed
Javery 1996 {published data only}
    1. 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. - PubMed
Jendoubi 2017 {published data only}
    1. 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. [DOI: 10.4103/1658-354X203027] - DOI - PMC - PubMed
Joly 2005 {published data only}
    1. 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. - PubMed
Joseph 2012 {published data only}
    1. 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. [DOI: 10.1093/ejcts/ezs398] - DOI - PubMed
Kafali 2004 {published data only}
    1. Kafali H, Aldemir B, Kaygusuz K, Gürsoy S, Kunt N. Small-dose ketamine decreases postoperative morphine requirements. European Journal of Anaesthesiology 2004;21:914. - PubMed
Kakinohana 2004 {published data only}
    1. 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. [DOI: ]
Kamal 2008 {published data only}
    1. 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.
Kapfer 2005 {published data only}
    1. Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M. Nefopam and ketamine comparably enhance postoperative analgesia. Anesthesia & Analgesia 2005;100(1):169-74. [DOI: 10.1213/01.ANE.0000138037.19757.ED] - DOI - PMC - PubMed
Karaman 2006 {published data only}
    1. 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. - PubMed
Kararmaz 2003 {published data only}
    1. 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. [DOI: 10.1213/01.ANE.0000080205.24285.36] - DOI - PubMed
Karcioglu 2013 {published data only}
    1. 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. [DOI: 10.1097/SLE.0b013e3182827f09] - DOI - PubMed
Katz 2004 {published data only}
    1. 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. [DOI: 10.1016/j.pain.2004.05.011] - DOI - PubMed
Kim 2013 {published data only}
    1. 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. [DOI: 10.4097/kjae.2013.64.6.524] - DOI - PMC - PubMed
Kim 2016 {published data only}
    1. 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. [DOI: 10.1097/MD.0000000000005485] - DOI - PMC - PubMed
Köse 2012 {published data only}
    1. 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. [DOI: ] - PubMed
Kudoh 2002 {published data only}
    1. 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. [DOI: 10.1213/01.ANE.0000020693.B7] - DOI - PubMed
Kwok 2004 {published data only}
    1. 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. [DOI: 10.1213/01.ANE.0000105911.66089.59] - DOI - PubMed
Kwon 2009 {published data only}
    1. 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. [DOI: 10.4097/kae.2009.57.5.604] - DOI - PubMed
Lahtinen 2004 {published data only}
    1. 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. [DOI: 10.1213/01.ANE.0000133913.07342.B9] - DOI - PubMed
Lak 2010 {published data only}
    1. 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.
Leal 2013 {published data only}
    1. 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. - PubMed
Leal 2015 {published data only}
    1. 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. [DOI: 10.1016/j.jclinane.2015.02.002] - DOI - PubMed
Lebrun 2006 {published data only}
    1. 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. - PubMed
Lee 2008 {published data only}
    1. 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.
Lehmann 2001 {published data only}
    1. 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. - PubMed
Lenzmeier 2008 {published data only}
    1. 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. - PubMed
Lin 2016 {published data only}
    1. 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. [DOI: 10.1007/s11596-016-1629-0] - DOI - PubMed
Lo 2008 {published data only}
    1. 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.
Loftus 2010 {published data only}
    1. 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. - PubMed
Mahran 2015 {published data only}
    1. 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. [DOI: 10.4103/1658-354X.154X.154697] - DOI - PMC - PubMed
Martinez 2014 {published data only}
    1. 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. [DOI: 10.1111/anae.12495] - DOI - PubMed
Mathisen 1999 {published data only}
    1. 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. - PubMed
McKay 2007 {published data only}
    1. 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. [DOI: 10.1111/j.1399-6576.2007.01436.x] - DOI - PubMed
Mebazaa MS 2008 {published data only}
    1. 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. - PubMed
Mendola 2012 {published data only}
    1. 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. - PubMed
Menigaux 2000 {published data only}
    1. 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. - PubMed
Menigaux 2001 {published data only}
    1. 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. - PubMed
Michelet 2007 {published data only}
    1. 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. [DOI: ] - PubMed
Miziara 2016 {published data only}
    1. 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. [DOI: 10.1155/2016/6918327] - DOI - PMC - PubMed
Murdoch 2002 {published data only}
    1. Murdoch CJ, Crooks BA, Miller CD. Effect of the addition of ketamine to morphine in patient-controlled analgesia. Anaesthesia 2002;57:484-8. [DOI: 10.1046/j.0003-2409.2001.02409.x] - DOI - PubMed
Nesek‐Adam 2012 {published data only}
    1. 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. - PubMed
Nielsen 2017 {published data only}
    1. 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. [DOI: 10.1097/j.pain.0000000000000782] - DOI - PubMed
Ögün 2001 {published data only}
    1. 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.
Ong 2001 {published data only}
    1. Ong EL, Osborne GA. Ketamine for co-induction of anaesthesia in oral surgery. Ambulatory Surgery 2001;9:131-5.
Ozhan 2013 {published data only}
    1. 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. [DOI: 10.4328/JCAM.2161] - DOI
Pacreu 2012 {published data only}
    1. 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. [DOI: 10.1111/j.1399-6576.2012.02743.x] - DOI - PubMed
Papaziogas 2001 {published data only}
    1. 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. [DOI: ] - PubMed
Parikh 2011 {published data only}
    1. 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. - PMC - PubMed
Patel 2016 {published data only}
    1. 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. [DOI: 10.1177/0218492316663359] - DOI - PubMed
Pirim 2006 {published data only}
    1. 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. - PubMed
Remérand 2009 {published data only}
    1. 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. [DOI: 10.1213/ANE.0b013e3181bdc8a0] - DOI - PubMed
Reza 2010 {published data only}
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Roytblat 1993 {published data only}
    1. 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. - PubMed
Safavi 2011 {published data only}
    1. 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. - PubMed
Sahin 2004 {published data only}
    1. 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.
Sen 2009 {published data only}
    1. 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. [DOI: 10.1213/ANE.0b013e3181b65ea0] - DOI - PubMed
Siddiqui 2015 {published data only}
    1. 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. [DOI: 10.4103/1658-354X.159468] - DOI - PMC - PubMed
Singh 2013 {published data only}
    1. 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. [DOI: 10.4103/0970-9185.119141] - DOI - PMC - PubMed
Snijdelaar 2004 {published data only}
    1. 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. - PubMed
Song 2013 {published data only}
    1. 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. [DOI: 10.1093/bja/aet192] - DOI - PubMed
Song 2014 {published data only}
    1. 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. [DOI: 10.4097/kjae.2014.66.1.44] - DOI - PMC - PubMed
Spreng 2010 {published data only}
    1. 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. [DOI: 10.1016/j.sjpain.2010.01.009] - DOI - PubMed
Stubhaug 1997 {published data only}
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Subramaniam 2011 {published data only}
    1. 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. - PubMed
Suzuki 1999 {published data only}
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Suzuki 2006 {published data only}
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Ünlügenc 2003 {published data only}
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Van Elstraete 2004 {published data only}
    1. 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. [DOI: 10.1111/j.1399-6576.2004.00399.x] - DOI - PubMed
Webb 2007 {published data only}
    1. 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. [DOI: 10.1213/01.ane.0000256961.01813.da] - DOI - PubMed
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Yalcin 2012 {published data only}
    1. 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. [DOI: 10.7150/ijms.4222] - DOI - PMC - PubMed
Yamauchi 2008 {published data only}
    1. 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. [DOI: 10.1213/ane.0b013e31817f1e4a] - DOI - PubMed
Yazigi 2012 {published data only}
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Yeom 2012 {published data only}
    1. 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. [DOI: 10.4097/kjae.2012.63.1.54] - DOI - PMC - PubMed
Ysasi 2010 {published data only}
    1. 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. [DOI: 10.1016/j.resed.2010.04.002] - DOI
Zakine 2008 {published data only}
    1. 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. [DOI: 10.1213/ane.0b013e3181732776] - DOI - PubMed

References to studies excluded from this review

Abrishamkar 2012 {published data only}
    1. 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. - PubMed
Adams 2003 {published data only}
    1. 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. [DOI: 10.1007/s00101-002-0440-4] - DOI - PubMed
Aghamohammadi 2012 {published data only}
    1. 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. [DOI: 10.5681/jcvtr.2012.016] - DOI - PMC - PubMed
Akca 2016 {published data only}
    1. 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. [DOI: 10.15537/smj.2016.1.14122] - DOI - PMC - PubMed
Avidan 2017 {published data only}
    1. 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. [DOI: 10.1016/S0140-6736(17)31467-8] - DOI - PMC - PubMed
Behdad 2011 {published data only}
    1. 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. [DOI: 10.3344/kjp.2011.24.3.137] - DOI - PMC - PubMed
Bentley 2005 {published data only}
    1. 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. - PubMed
Bilgin 2005 {published data only}
    1. 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. [DOI: 10.1016/j.jclinane.2005.04.005] - DOI - PubMed
Clausen 1975 {published data only}
    1. Clausen L, Sinclair DM, Van Hasselt CH. Intravenous ketamine for postoperative analgesia. South African Medical Journal 1975;49(35):1437-40. - PubMed
Edwards 1993 {published data only}
    1. 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. [DOI: 10.1111/j.1365-2044.1993.tb06849.x] - DOI - PubMed
Gillies 2007 {published data only}
    1. 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. - PubMed
Guan 2008 {published data only}
    1. 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.
Heinke 1999 {published data only}
    1. Heinke W, Grimm D. Preemptive effects caused by co-analgesia with ketamine in gynecological laparotomies? Anaesthesiologie und Reanimation 1999;24(3):60-4. - PubMed
Hong 2011 {published data only}
    1. 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. [DOI: 10.4097/kjae.2011.61.3.238] - DOI - PMC - PubMed
Ito 1974 {published data only}
    1. Ito Y, Ichiyanagi K. Post-operative pain relief with ketamine infusion. Anaesthesia 1974;29:222-9. - PubMed
Jahangir 1993 {published data only}
    1. 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. - PubMed
Jensen 2008 {published data only}
    1. 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. [DOI: 10.1111/j.1399-6576.2008.01602.x] - DOI - PubMed
Jiang 2016 {published data only}
    1. 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. [DOI: 10.1007/s00540-015-2096-7] - DOI - PubMed
Joachimmson 1986 {published data only}
    1. Joachimmsson PO, Hedstrand U, Eklund A. Low-dose ketamine infusion for analgesia during postoperative ventilator treatment. Acta Anaesthesiologica Scandinavica 1986;30(8):697-702. [DOI: 10.1111/j.1399-6576.1986.tb02505.x] - DOI - PubMed
Kadic 2016 {published data only}
    1. 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. [DOI: 10.4103/0970-9185.194762] - DOI - PMC - PubMed
Kim 2001 {published data only}
    1. 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. [DOI: 10.4097/kjae.2001.40.4.509] - DOI
Kim 2005 {published data only}
    1. 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. [DOI: 10.4097/kjae.2005.48.2.163] - DOI
Kollender 2008 {published data only}
    1. 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. [DOI: 10.1016/j.ejca.2008.02.021] - DOI - PubMed
Kose 2008 {published data only}
    1. 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. [DOI: 10.1213/01.ane.0000296458.16313.7c] - DOI - PubMed
Launo 2004 {published data only}
    1. 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. - PubMed
Lee 2005 {published data only}
    1. 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. [DOI: 10.4097/kjae.2005.49.1.81] - DOI
Lee 2006 {published data only}
    1. 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.
Lee 2013 {published data only}
    1. 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. [DOI: 10.4097/kjae.2013.65.6S.S132] - DOI - PMC - PubMed
Lee 2014 {published data only}
    1. 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. [DOI: 10.4097/kjae.2014.66.3.222] - DOI - PMC - PubMed
Liang 2006 {published data only}
    1. 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. - PubMed
Lux 2009 {published data only}
    1. 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. [DOI: 10.1007/s00101-009-1607-z] - DOI - PubMed
Malek 2006 {published data only}
    1. 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.
Maurset 1989 {published data only}
    1. Maurset A, Skoglund LA, Hustveit O, Oye I. Comparison of ketamine and pethidine in experimental and postoperative pain. Pain 1989;36:37-41. [DOI: 10.1016/0304-3959(89)90109-7] - DOI - PubMed
Nayar 2009 {published data only}
    1. 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. - PubMed
Ndoye 2008 {published data only}
    1. 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. - PubMed
Nesher 2008 {published data only}
    1. 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. [DOI: 10.1016/j.phrs.2008.06.003] - DOI - PubMed
Nesher 2009 {published data only}
    1. 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. [DOI: 10.1378/chest.08-0246] - DOI - PubMed
Nikolayev 2008 {published data only}
    1. Nikolayev AP, Nikoda VV, Svetlov VA. Multimodal approach to postoperative analgesia in patients with neuropathic pain. Anesteziologiia i Reanimatologiia 2008;5:99-103. - PubMed
Nitta 2013 {published data only}
    1. 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. [DOI: 10.1016/j.aat.2013.03.003] - DOI - PubMed
Nourozi 2010 {published data only}
    1. 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. [DOI: 10.3923/pjbs.2010.1214.1218] - DOI - PubMed
Oliveira 2005 {published data only}
    1. Oliveira CMB, Issy AM, Sakata RK, Garcia JBS, Martins CR. Preemptive effect of IV S(+) -ketamine for hysterectomy. Acute Pain 2005;7:139-43. [DOI: 10.1016/j.acpain.2005.08.001] - DOI
Owen 1987 {published data only}
    1. Owen H, Reekie RM, Clements JA, Watson R, Nimmo WS. Analgesia from morphine and ketamine. Anaesthesia 1987;42:1051-6. [DOI: 10.1111/j.1365-2044.1987.tb05167.x] - DOI - PubMed
Park 2004 {published data only}
    1. 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. [DOI: 10.4097/kjae.2004.46.5.517] - DOI
Perrin 2009 {published data only}
    1. 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. - PubMed
Reeves 2001 {published data only}
    1. 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. [DOI: 10.1097/00000539-200107000-00025] - DOI - PubMed
Sadove 1971 {published data only}
    1. Sadove MS, Shulman M, Hatano S, Fevold N. Analgesic effects of ketamine administered in subdissociative doses. Anesthesia and Analgesia 1971;50(3):452-7. - PubMed
Sollazzi 2008 {published data only}
    1. 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. [DOI: 10.1016/j.soard.2008.09.018] - PubMed
Song 2004 {published data only}
    1. 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.
Sveticic 2008 {published data only}
    1. 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. [DOI: 10.1213/01.ane.0000289637.11065.8f] - DOI - PubMed
Talu 2002 {published data only}
    1. 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.
Thomas 2012 {published data only}
    1. 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. - PubMed
Tverskoy 1994 {published data only}
    1. 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. - PubMed
Tverskoy 1996 {published data only}
    1. 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. [DOI: 10.1016/S0304-3940(96)12922-0] - DOI - PubMed
Ünlügenc 2002 {published data only}
    1. 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. - PubMed
Urban 2008 {published data only}
    1. 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. [DOI: 10.1007/s11420-007-9069-9] - DOI - PMC - PubMed
Weinbroum 2003 {published data only}
    1. 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. [DOI: 10.1213/01.ANE.0000048088.17761.B4] - DOI - PubMed
Wilder‐Smith 1998 {published data only}
    1. 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. [DOI: 10.1213/00000539-199801000-00019] - DOI - PubMed
Xie 2003 {published data only}
    1. 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. - PubMed
Xu 2017 {published data only}
    1. 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. [DOI: 10.1007/s00404-017-4334-8] - DOI - PubMed

References to studies awaiting assessment

Lee 2018 {published data only}
    1. 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. - PMC - PubMed
Lou 2017 {published data only}
    1. 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. - PubMed
Moon 2018 {published data only}
    1. 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. - PubMed

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References to other published versions of this review

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