Prophylactic Analgesic Effect of Adding Ketamine to Bupivacaine in Lumbar Fusion Surgery: A Randomized Controlled Trial
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Abstract
Background: This randomized controlled trial evaluated the analgesic effect of adding subcutaneous ketamine to bupivacaine in lumbar fusion surgery.
Methods: 46 adult patients were randomized to receive subcutaneous bupivacaine with or without ketamine before incision. Pain scores (VAS), time to first rescue analgesia, opioid use, extubation time, and patient satisfaction were assessed.
Results: The ketamine group had higher early postoperative pain (30 and 60 min; P < 0.05) but showed prolonged time to rescue analgesia (P = 0.037) and reduced opioid use (not statistically significant). Extubation time was significantly longer. Satisfaction scores were similar.
Conclusion: Subcutaneous ketamine delayed opioid use but increased early pain and extubation time. It may be considered in selected patients, pending further research.
[1] Hassani V, Rahimzadeh A, Nikoubakht N, Sayarifard A, Latifi K. The Effect of Remifentanil– Propofol Compared with Fentanyl– Propofol on Urine Output in Patients Undergoing Lumbar Posterior Spinal Fusion. Arch Anesth Crit Care. 2016; 2(2):175-8.
[2] Martin BI, Mirza SK, Spina N, Spiker WR, Lawrence B, Brodke DS. Trends in Lumbar Fusion Procedure Rates and Associated Hospital Costs for Degenerative Spinal Diseases in the United States, 2004 to 2015. Spine (Phila Pa 1976). 2019; 44(5):369-76.
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[4] Dorow M, Löbner M, Stein J, Konnopka A, Meisel HJ, et al. Risk Factors for Postoperative Pain Intensity in Patients Undergoing Lumbar Disc Surgery: A Systematic Review. PLoS One. 2017; 12(1):e0170303.
[5] Zhang Z, Han T, Xu H, Wei Z, Li W, Zhang Y, et al. Nonsteroidal anti-inflammatory drugs for postoperative pain control after lumbar spine surgery: a meta-analysis of randomized controlled trials. J Clin Anesth. 2017; 43:84-9.
[6] Lavand'homme P. Transition from acute to chronic pain after surgery. Pain. 2017; 158 Suppl 1:S50-S54.
[7] Rosenbloom BN, Frederiksen SD, Wang V, Birnie KA, Park CS, Gordon G, et al. Prevalence of and recommendation for measuring chronic postsurgical pain in children: an updated systematic review and meta-analysis. Reg Anesth Pain Med. 2025; 50(2):132-43.
[8] Harned M, Sloan P. Safety concerns with long-term opioid use. Expert Opin Drug Saf. 2016; 15(7):955-62.
[9] Joshi GP. Rational Multimodal Analgesia for Perioperative Pain Management. Curr Pain Headache Rep. 2023; 27(8):227-37.
[10] Chahar P, Cummings KC 3rd. Liposomal bupivacaine: a review of a new bupivacaine formulation. J Pain Res. 2012; 5:257-64.
[11] Ilfeld BM, Eisenach JC, Gabriel RA. Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Anesthesiology. 2021; 134(2):283-344.
[12] Seo EH, Piao L, Cho EH, Hong SW, Kim SH. The Effect of Ketamine on Endoplasmic Reticulum Stress in Rats with Neuropathic Pain. Int J Mol Sci. 2023; 24(6):5336.
[13] Rizk RS, Refky MA, Zanfaly HI, Ibraheam AM. Postoperative analgesic effect of using bupivacaine versus bupivacaine with dexmedetomidine or ketamine in cesarean section operations. Egypt J Hosp Med. 2022; 88(1):3374-9.
[14] Mahdi AH, Kahloul M, Mohammed MJ, Mohammed AK, Mahdi A, Mohammed M, et al. Effects of Ketamine and Tramadol As Adjuvants to Bupivacaine in Spinal Anesthesia for Unilateral Open Ovarian Cystectomy: A Randomized Controlled Trial. Cureus. 2024; 16(2).
[15] Sahoo AK, Misra S, Behera BK, Srinivasan A, Jena SS, Mohanty MK. Subanesthetic intravenous ketamine vs. caudal bupivacaine for postoperative analgesia in children undergoing infra-umbilical surgeries: a non-inferiority randomized, single-blind controlled trial. Korean J Anesthesiol. 2022; 75(2):178-84.
[16] Suzuki M, Kinoshita T, Kikutani T, Yokoyama K, Inagi T, Sugimoto K, et al. Determining the plasma concentration of ketamine that enhances epidural bupivacaine-and-morphine-induced analgesia. Anesth Analg. 2005; 101(3):777-84.
[17] De Kock M, Lavand'homme P, Waterloos H. 'Balanced analgesia' in the perioperative period: is there a place for ketamine? Pain. 2001; 92(3):373-80.
[18] Aksoy H, Gökahmetoğlu G, Ak M, Aksoy Ü. Subcutaneous wound infiltration of ketamine is superior to bupivacaine in terms of pain perception and opioid consumption after cesarean section: a double-blinded randomized placebo-controlled clinical trial. Eur Rev Med Pharmacol Sci. 2023; 27(18):8860-7.
[19] Singhatanadgige W, Chancharoenchai T, Honsawek S, Kotheeranurak V, Tanavalee C, Limthongkul W. No Difference in Pain After Spine Surgery with Local Wound Filtration of Morphine and Ketorolac: A Randomized Controlled Trial. Clin Orthop Relat Res. 2020; 478(12):2823-9.
[20] Randall DJ, Zhang Y, Li H, Hubbard JC, Kazmers NH. Establishing the Minimal Clinically Important Difference and Substantial Clinical Benefit for the Pain Visual Analog Scale in a Postoperative Hand Surgery Population. J Hand Surg Am. 2022; 47(7):645-53.
[21] Gautam SN, Poudel A, Agrawal A, Shah J, Koju S. Evaluation of Postoperative Analgesic Efficacy of Intraperitoneal Ketamine plus Bupivacaine in Laparoscopic Surgery. Nepal Med Coll J. 2024; 26(4):319-25.
[22] Menkiti ID, Desalu I, Kushimo OT. Low-dose intravenous ketamine improves postoperative analgesia after caesarean delivery with spinal bupivacaine in African parturients. Int J Obstet Anesth. 2012; 21(3):217-21.
[23] Pedersen JL, Galle TS, Kehlet H. Peripheral analgesic effects of ketamine in acute inflammatory pain. Anesthesiology. 1998; 89(1):58-66.
[24] Tan PH, Cheng JT, Kuo CH, Tseng FJ, Chung HC, Wu JI, et al. Preincisional subcutaneous infiltration of ketamine suppresses postoperative pain after circumcision surgery. Clin J Pain. 2007; 23(3):214-8.
[25] Andrade C. Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency? J Clin Psychiatry. 2017; 78(7):e852-e857.
[26] Deng B, Yang D, Wu H, Wang L, Wu R, Zhu H, et al. Ketamine inhibits TNF-α-induced cecal damage by enhancing RIP1 ubiquitination to attenuate lethal SIRS. Cell Death Discov. 2022; 8(1):72.
[27] Kaye AD, Banister RE, Fox CJ, Ibrahim IN, Nossaman BD. Analysis of ketamine responses in the pulmonary vascular bed of the cat. Crit Care Med. 2000; 28(4):1077-82.
[28] Vlisides PE, Bel-Bahar T, Nelson A, Chilton K, Smith E, Janke E, et al. Subanaesthetic ketamine and altered states of consciousness in humans. Br J Anaesth. 2018; 121(1):249-59.
[29] 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. Br J Anaesth. 1998; 81(5):707-12.
[30] Brinck EC, Tiippana E, Heesen M, Bell RF, Straube S, Moore RA, et al. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018; 12(12):CD012033.
[31] Zhang A, Zhou Y, Zheng X, Zhou W, Gu Y, Jiang Z, et al. Effects of S-ketamine added to patient-controlled analgesia on early postoperative pain and recovery in patients undergoing thoracoscopic lung surgery: A randomized double-blinded controlled trial. J Clin Anesth. 2024; 92:111299.
[32] 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.
[33] Gohain BB, Hazarika A. Evaluation of the Efficacy of Intravenous Ketamine on Prevention of Hypotension During Spinal Anaesthesia in Patients with benign Prostatic Hyperplasia. Int J Contemp Med Res. 2020; 7(3).
[34] Majeed K, Malik UE, Hafiz A, Hussain F, Munir H, us Saqib N. Comparison of Hemodynamic Stability of Patients Undergoing Appendectomy under Spinal Anesthesia versus Blend of Ketamine and Midazolam with Spinal Anesthesia. Pak Armed Forces Med J. 2023; 73(4):1128.
[2] Martin BI, Mirza SK, Spina N, Spiker WR, Lawrence B, Brodke DS. Trends in Lumbar Fusion Procedure Rates and Associated Hospital Costs for Degenerative Spinal Diseases in the United States, 2004 to 2015. Spine (Phila Pa 1976). 2019; 44(5):369-76.
[3] Fritsch CG, Ferreira ML, Maher CG, Herbert RD, Pinto RZ, Koes B, et al. The clinical course of pain and disability following surgery for spinal stenosis: a systematic review and meta-analysis of cohort studies. Eur Spine J. 2017; 26(2):324-35.
[4] Dorow M, Löbner M, Stein J, Konnopka A, Meisel HJ, et al. Risk Factors for Postoperative Pain Intensity in Patients Undergoing Lumbar Disc Surgery: A Systematic Review. PLoS One. 2017; 12(1):e0170303.
[5] Zhang Z, Han T, Xu H, Wei Z, Li W, Zhang Y, et al. Nonsteroidal anti-inflammatory drugs for postoperative pain control after lumbar spine surgery: a meta-analysis of randomized controlled trials. J Clin Anesth. 2017; 43:84-9.
[6] Lavand'homme P. Transition from acute to chronic pain after surgery. Pain. 2017; 158 Suppl 1:S50-S54.
[7] Rosenbloom BN, Frederiksen SD, Wang V, Birnie KA, Park CS, Gordon G, et al. Prevalence of and recommendation for measuring chronic postsurgical pain in children: an updated systematic review and meta-analysis. Reg Anesth Pain Med. 2025; 50(2):132-43.
[8] Harned M, Sloan P. Safety concerns with long-term opioid use. Expert Opin Drug Saf. 2016; 15(7):955-62.
[9] Joshi GP. Rational Multimodal Analgesia for Perioperative Pain Management. Curr Pain Headache Rep. 2023; 27(8):227-37.
[10] Chahar P, Cummings KC 3rd. Liposomal bupivacaine: a review of a new bupivacaine formulation. J Pain Res. 2012; 5:257-64.
[11] Ilfeld BM, Eisenach JC, Gabriel RA. Clinical Effectiveness of Liposomal Bupivacaine Administered by Infiltration or Peripheral Nerve Block to Treat Postoperative Pain. Anesthesiology. 2021; 134(2):283-344.
[12] Seo EH, Piao L, Cho EH, Hong SW, Kim SH. The Effect of Ketamine on Endoplasmic Reticulum Stress in Rats with Neuropathic Pain. Int J Mol Sci. 2023; 24(6):5336.
[13] Rizk RS, Refky MA, Zanfaly HI, Ibraheam AM. Postoperative analgesic effect of using bupivacaine versus bupivacaine with dexmedetomidine or ketamine in cesarean section operations. Egypt J Hosp Med. 2022; 88(1):3374-9.
[14] Mahdi AH, Kahloul M, Mohammed MJ, Mohammed AK, Mahdi A, Mohammed M, et al. Effects of Ketamine and Tramadol As Adjuvants to Bupivacaine in Spinal Anesthesia for Unilateral Open Ovarian Cystectomy: A Randomized Controlled Trial. Cureus. 2024; 16(2).
[15] Sahoo AK, Misra S, Behera BK, Srinivasan A, Jena SS, Mohanty MK. Subanesthetic intravenous ketamine vs. caudal bupivacaine for postoperative analgesia in children undergoing infra-umbilical surgeries: a non-inferiority randomized, single-blind controlled trial. Korean J Anesthesiol. 2022; 75(2):178-84.
[16] Suzuki M, Kinoshita T, Kikutani T, Yokoyama K, Inagi T, Sugimoto K, et al. Determining the plasma concentration of ketamine that enhances epidural bupivacaine-and-morphine-induced analgesia. Anesth Analg. 2005; 101(3):777-84.
[17] De Kock M, Lavand'homme P, Waterloos H. 'Balanced analgesia' in the perioperative period: is there a place for ketamine? Pain. 2001; 92(3):373-80.
[18] Aksoy H, Gökahmetoğlu G, Ak M, Aksoy Ü. Subcutaneous wound infiltration of ketamine is superior to bupivacaine in terms of pain perception and opioid consumption after cesarean section: a double-blinded randomized placebo-controlled clinical trial. Eur Rev Med Pharmacol Sci. 2023; 27(18):8860-7.
[19] Singhatanadgige W, Chancharoenchai T, Honsawek S, Kotheeranurak V, Tanavalee C, Limthongkul W. No Difference in Pain After Spine Surgery with Local Wound Filtration of Morphine and Ketorolac: A Randomized Controlled Trial. Clin Orthop Relat Res. 2020; 478(12):2823-9.
[20] Randall DJ, Zhang Y, Li H, Hubbard JC, Kazmers NH. Establishing the Minimal Clinically Important Difference and Substantial Clinical Benefit for the Pain Visual Analog Scale in a Postoperative Hand Surgery Population. J Hand Surg Am. 2022; 47(7):645-53.
[21] Gautam SN, Poudel A, Agrawal A, Shah J, Koju S. Evaluation of Postoperative Analgesic Efficacy of Intraperitoneal Ketamine plus Bupivacaine in Laparoscopic Surgery. Nepal Med Coll J. 2024; 26(4):319-25.
[22] Menkiti ID, Desalu I, Kushimo OT. Low-dose intravenous ketamine improves postoperative analgesia after caesarean delivery with spinal bupivacaine in African parturients. Int J Obstet Anesth. 2012; 21(3):217-21.
[23] Pedersen JL, Galle TS, Kehlet H. Peripheral analgesic effects of ketamine in acute inflammatory pain. Anesthesiology. 1998; 89(1):58-66.
[24] Tan PH, Cheng JT, Kuo CH, Tseng FJ, Chung HC, Wu JI, et al. Preincisional subcutaneous infiltration of ketamine suppresses postoperative pain after circumcision surgery. Clin J Pain. 2007; 23(3):214-8.
[25] Andrade C. Ketamine for Depression, 4: In What Dose, at What Rate, by What Route, for How Long, and at What Frequency? J Clin Psychiatry. 2017; 78(7):e852-e857.
[26] Deng B, Yang D, Wu H, Wang L, Wu R, Zhu H, et al. Ketamine inhibits TNF-α-induced cecal damage by enhancing RIP1 ubiquitination to attenuate lethal SIRS. Cell Death Discov. 2022; 8(1):72.
[27] Kaye AD, Banister RE, Fox CJ, Ibrahim IN, Nossaman BD. Analysis of ketamine responses in the pulmonary vascular bed of the cat. Crit Care Med. 2000; 28(4):1077-82.
[28] Vlisides PE, Bel-Bahar T, Nelson A, Chilton K, Smith E, Janke E, et al. Subanaesthetic ketamine and altered states of consciousness in humans. Br J Anaesth. 2018; 121(1):249-59.
[29] 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. Br J Anaesth. 1998; 81(5):707-12.
[30] Brinck EC, Tiippana E, Heesen M, Bell RF, Straube S, Moore RA, et al. Perioperative intravenous ketamine for acute postoperative pain in adults. Cochrane Database Syst Rev. 2018; 12(12):CD012033.
[31] Zhang A, Zhou Y, Zheng X, Zhou W, Gu Y, Jiang Z, et al. Effects of S-ketamine added to patient-controlled analgesia on early postoperative pain and recovery in patients undergoing thoracoscopic lung surgery: A randomized double-blinded controlled trial. J Clin Anesth. 2024; 92:111299.
[32] 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.
[33] Gohain BB, Hazarika A. Evaluation of the Efficacy of Intravenous Ketamine on Prevention of Hypotension During Spinal Anaesthesia in Patients with benign Prostatic Hyperplasia. Int J Contemp Med Res. 2020; 7(3).
[34] Majeed K, Malik UE, Hafiz A, Hussain F, Munir H, us Saqib N. Comparison of Hemodynamic Stability of Patients Undergoing Appendectomy under Spinal Anesthesia versus Blend of Ketamine and Midazolam with Spinal Anesthesia. Pak Armed Forces Med J. 2023; 73(4):1128.
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How to Cite
1.
Honarmand A, Mahmoodkhani M, Nazemroaya B, Ahmadian A. Prophylactic Analgesic Effect of Adding Ketamine to Bupivacaine in Lumbar Fusion Surgery: A Randomized Controlled Trial. Arch Anesth & Crit Care. 2026;.
