Ketamine and Spine Surgery – Review
DOI:
https://doi.org/10.66166/cjaim.2.1.2Keywords:
ketamine, spine surgery, opioids, pain managementAbstract
Introduction: Various multimodal analgesic approaches have been proposed for spine surgery. This article aims to review the evidence regarding the effect of perioperative ketamine on postoperative opioid consumption, pain scores, and side effects.
Materials and Methods: We included clinical trials in the adult population. Our primary outcome was pain management. Randomized controlled trials published in the English language from the January 1995 to September 2005 assessing postoperative pain after spine surgery were identified from the MEDLINE database.
Results: A total of 16 clinical trials were selected for inclusion in the Review.
Conclusion: Perioperative low doses of ketamine demonstrated analgesic and opioid-sparing effects with no increased adverse events after spine surgery. Further studies of qualitative randomized controlled trials are required to assess the optimal protocol of ketamine administration for postoperative pain relief.
References
1. Waelkens P, Alsabbagh E, Sauter A, Joshi GP, Beloeil H; PROSPECT Working group∗∗ of the European Society of Regional Anaesthesia and Pain therapy (ESRA). Pain management after complex spine surgery: A systematic review and procedure-specific postoperative pain management recommendations. Eur J Anaesthesiol. 2021;38(9):985-94. DOI: 10.1097/EJA.0000000000001448.
2. Czarnetzki C, Desmeules J, Tessitore E, Faundez A, Chabert J, Daali Y, et al. Perioperative intravenous low-dose ketamine for neuropathic pain after major lower back surgery: A randomized, placebo-controlled study. Eur J Pain. 2020;24(3):555-67. DOI: 10.1002/ejp.1507.
3. Brinck ECV, Maisniemi K, Kankare J, Tielinen L, Tarkkila P, Kontinen VK. Analgesic Effect of Intraoperative Intravenous S-Ketamine in Opioid-Naïve Patients After Major Lumbar Fusion Surgery Is Temporary and Not Dose-Dependent: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Anesth Analg. 2021;132(1):69-79. DOI: 10.1213/ANE.0000000000004729.
4. Dinsmore M, Nijs K, Plitman E, Al Azazi E, Venkatraghavan L, Ladha K, et al. Oral ketamine for acute postoperative analgesia (OKAPA) trial: A randomized controlled, single center pilot study. J Clin Anesth. 2025;100:111690. DOI: 10.1016/j.jclinane.2024.111690.
5. Murphy GS, Avram MJ, Greenberg SB, Benson J, Bilimoria S, Maher CE, et al. Perioperative Methadone and Ketamine for Postoperative Pain Control in Spinal Surgical Patients: A Randomized, Double-blind, Placebo-controlled Trial. Anesthesiology. 2021;134(5):697-708. DOI: 10.1097/ALN.0000000000003743.
6. Rajan S, Devarajan J, Krishnaney A, George A, Rasouli JJ, Avitsian R. Opioid Alternatives in Spine Surgery: A Narrative Review. J Neurosurg Anesthesiol. 2022;34(1):3-13. DOI: 10.1097/ANA.0000000000000708.
7. Podder D, Stala O, Hirani R, Karp AM, Etienne M. Comprehensive Approaches to Pain Management in Postoperative Spinal Surgery Patients: Advanced Strategies and Future Directions. Neurol Int. 2025 ;17(6):94. DOI: 10.3390/neurolint17060094.
8. Zhou L, Yang H, Hai Y, Cheng Y. Perioperative Low-Dose Ketamine for Postoperative Pain Management in Spine Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Pain Res Manag. 2022;2022:1507097. DOI: 10.1155/2022/1507097.
9. Edinoff AN, Askins D, Bobo E, White KL, Eswani Z, Jackson ED, et al. The Emerging Role of Ketamine in Acute Postoperative Pain Management. Curr Pain Headache Rep. 2023;27(9):387-397. DOI: 10.1007/s11916-023-01134-1.
10. Zhang Q, Ma Y, Liu J, Liu H. Opioid-Sparing and Opioid-Free Anaesthesia: A Review of Clinical Evidence and Implementation Considerations. Br J Hosp Med (Lond). 2026;87(5):54057. DOI: 10.31083/BJHM54057.
11. Rivkin A, Rivkin MA. Perioperative nonopioid agents for pain control in spinal surgery. Am J Health Syst Pharm. 2014;71(21):1845-57. DOI: 10.2146/ajhp130688.
12. 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 Med. 2011;12(8):1276-83. DOI: 10.1111/j.1526-4637.2011.01144.x.
13. Pendi Arif, Field Ryan, Farhan Saifal-Deen, Eichler Martin, Bederman S. Samuel. Perioperative Ketamine for Analgesia in Spine Surgery: A Meta-analysis of Randomized Controlled Trials. SPINE 2018;43(5):E299-E307. DOI: 10.1097/BRS.0000000000002318
14. Radvansky BM, Shah K, Parikh A, Sifonios AN, Le V, Eloy JD. Role of ketamine in acute postoperative pain management: a narrative review. Biomed Res Int. 2015;2015:749837. DOI: 10.1155/2015/749837.
15. Viderman D, Mukazhan D, Kapessova K, Tungushpayev M, Badenes R. The Impact of Ketamine on Outcomes in Acute Pain Management: An Umbrella Review. J Clin Med. 2024 ;13(24):7699. DOI: 10.3390/jcm13247699.
16. Michael A. Gropper, Lars I. Eriksson, Lee A. Fleisher, Neal H. Cohen, Kate Leslie, Oluwaseun Johnson-Akeju. Miller's Anesthesia, 2-Volume Set. 10th Edition - September 15, 2023.
17. Hou NN, Zhang MY, Zhang YW, Wu HJ, Luo H, Yang H. Safety and efficacy of low-dose esketamine weakly opioidized anesthesia in elderly patients with lumbar spinal stenosis undergoing surgery: a prospective, double-blind randomized controlled trial. BMC Anesthesiol. 2025;25(1):57. DOI: 10.1186/s12871-025-02908-3.
18. Licina A, Silvers A, Laughlin H, Russell J, Wan C. Pathway for enhanced recovery after spinal surgery-a systematic review of evidence for use of individual components. BMC Anesthesiol. 2021;21(1):74. DOI: 10.1186/s12871-021-01281-1.
19. 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 Anaesthesiol Scand. 2012;56(10):1250-6.DOI: 10.1111/j.1399-6576.2012.02743.x.
20. 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. Anesth Analg. 2008;107(3):1041-4. DOI: 10.1213/ane.0b013e31817f1e4a.
21. Zhang Y, Cui F, Ma JH, Wang DX. Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial. Br J Anaesth. 2023;131(2):385-96. DOI: 10.1016/j.bja.2023.05.001.
22. Garg N, Panda NB, Gandhi KA, 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. J Neurosurg Anesthesiol. 2016;28(1):27-31. DOI: 10.1097/ANA.0000000000000193.
23. Brinck ECV, Virtanen T, Mäkelä S, Soini V, Hynninen VV, Mulo J, et al. S-ketamine in patient-controlled analgesia reduces opioid consumption in a dose-dependent manner after major lumbar fusion surgery: A randomized, double-blind, placebo-controlled clinical trial. PLoS One. 2021;16(6):e0252626. DOI: 10.1371/journal.pone.0252626.
24. Nielsen RV, Fomsgaard JS, Nikolajsen L, Dahl JB, Mathiesen O. Intraoperative S-ketamine for the reduction of opioid consumption and pain one year after spine surgery: A randomized clinical trial of opioid-dependent patients. Eur J Pain. 2019;23(3):455-60. DOI: 10.1002/ejp.1317.
25. 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 Anaesthesiol Taiwan. 2013;51(1):14-27. DOI: 10.1016/j.aat.2013.03.003.
26. Song JW, Shim 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. Br J Anaesth. 2013;111(4):630-5. DOI: 10.1093/bja/aet192.
27. 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(3):639-46. DOI: 10.1097/ALN.0b013e3181e90914.
28. Aveline C, Hetet HL, Vautier P, Gautier JF, Bonnet F. Peroperative ketamine and morphine for postoperative pain control after lumbar disk surgery. Eur J Pain. 2006;10(7):653-8. DOI: 10.1016/j.ejpain.2005.10.005.
29. Maheshwari K, Avitsian R, Sessler DI, Makarova N, Tanios M, Raza S, et al. Multimodal Analgesic Regimen for Spine Surgery: A Randomized Placebo-controlled Trial. Anesthesiology. 2020;132(5):992-1002. DOI: 10.1097/ALN.0000000000003143.
30. Schwenk ES, Goldberg SF, Patel RD, Zhou J, Adams DR, Baratta JL, et al. Adverse Drug Effects and Preoperative Medication Factors Related to Perioperative Low-Dose Ketamine Infusions. Reg Anesth Pain Med. 2016;41(4):482-7. DOI: 10.1097/AAP.0000000000000416.
31. Meyer-Frießem CH, Lipke E, Weibel S, Kranke P, Reichl S, Pogatzki-Zahn EM, et al. Perioperative ketamine for postoperative pain management in patients with preoperative opioid intake: A systematic review and meta-analysis. J Clin Anesth. 2022;78:110652. DOI: 10.1016/j.jclinane.2022.110652.
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Copyright (c) 2026 Ivan Krezić, Marin Lozic, Marijana Matas, Niksa Peric, Vasilije Stambolija, Miroslav Scap (Author)
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