Combined General/Epidural Anesthesia vs. General Anesthesia on Postoperative Cytokines: A Review and Meta-Analysis
Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Objectives
2.2. Search Strategy and Study Selection Criteria
2.3. Data Extraction
2.4. Statistical Analyses
3. Results
3.1. Description of Included Studies
3.2. IL-6 24 Hours After Surgery
3.3. TNF-α 24 Hours After Surgery
3.4. CRP 24 Hours After Surgery
3.5. IL-6 at the End of Surgery
3.6. TNF-α at the End of Surgery
3.7. CRP at the End of Surgery
3.8. Cortisol Levels After Surgery
3.9. Other Interleukin Levels After Surgery
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
GA | general anesthesia |
EA | epidural anesthesia |
CRP | C-reactive protein |
IL-6 | interleukin-6 |
TNF-α | tumor necrosis factor-α |
SMD | standardized mean differences |
References
- Desborough, J.P. The stress response to trauma and surgery. Br. J. Anaesth. 2000, 85, 109–117. [Google Scholar] [CrossRef] [PubMed]
- Sheeran, P.; Hall, G.M. Cytokines in anaesthesia. Br. J. Anaesth. 1997, 78, 201–219. [Google Scholar] [CrossRef] [PubMed]
- Dantzer, R.; O’Connor, J.C.; Freund, G.G.; Johnson, R.W.; Kelley, K.W. From inflammation to sickness and depression: When the immune system subjugates the brain. Nat. Rev. Neurosci. 2008, 9, 46–56. [Google Scholar] [CrossRef] [PubMed]
- Hsing, C.; Wang, J. Clinical implication of perioperative inflammatory cytokine alteration. Acta Anaesthesiol. Taiwanica Off. J. Taiwan Soc. Anesthesiol. 2015, 53, 23–28. [Google Scholar] [CrossRef] [PubMed]
- Angele, M.K.; Faist, E. Clinical review: Immunodepression in the surgical patient and increased susceptibility to infection. Crit. Care 2002, 6, 298–305. [Google Scholar] [CrossRef] [PubMed]
- Shimazui, T.; Oami, T.; Shimada, T.; Tomita, K.; Nakada, T.A. Age-dependent differences in the association between blood interleukin-6 levels and mortality in patients with sepsis: A retrospective observational study. J. Intensive Care 2025, 13, 3. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Watt, D.G.; McSorley, S.T.; Park, J.H.; Horgan, P.G.; McMillan, D.C. A Postoperative Systemic Inflammation Score Predicts Short- and Long-Term Outcomes in Patients Undergoing Surgery for Colorectal Cancer. Ann. Surg. Oncol. 2017, 24, 1100–1109. [Google Scholar] [CrossRef] [PubMed]
- McSorley, S.T.; Watt, D.G.; Horgan, P.G.; McMillan, D.C. Postoperative Systemic Inflammatory Response, Complication Severity, and Survival Following Surgery for Colorectal Cancer. Ann. Surg. Oncol. 2016, 23, 2832–2840. [Google Scholar] [CrossRef] [PubMed]
- Desmond, F.; McCormack, J.; Mulligan, N.; Stokes, M.; Buggy, D.J. Effect of anaesthetic technique on immune cell infiltration in breast cancer: A follow-up pilot analysis of a prospective, randomised, investigator-masked study. Anticancer Res. 2015, 35, 1311–1319. [Google Scholar] [PubMed]
- Liang, X.; Liu, R.; Chen, C.; Ji, F.; Li, T. Opioid System Modulates the Immune Function: A Review. Transl. Perioper. Pain Med. 2016, 1, 5. [Google Scholar] [PubMed]
- Stenger, M.; Fabrin, A.; Schmidt, H.; Greisen, J.; Erik, M.P.; Jakobsen, C. High thoracic epidural analgesia as an adjunct to general anesthesia is associated with better outcome in low-to-moderate risk cardiac surgery patients. J. Cardiothorac. Vasc. Anesth. 2013, 27, 1301–1309. [Google Scholar] [CrossRef] [PubMed]
- Wijeysundera, D.; Beattie, W.; Austin, P.; Hux, J.; Laupacis, A. Epidural anaesthesia and survival after intermediate-to-high risk non-cardiac surgery: A population-based cohort study. Lancet 2008, 372, 562–569. [Google Scholar] [CrossRef] [PubMed]
- Wang, S.; Xing, H.; Xu, X. Comparison of midazolam and dexmedetomidine combined with thoracic paravertebral block in hemodynamics, inflammation and stress response, and cognitive function in elderly lung cancer patients. Int. Immunopharmacol. 2025, 147, 113961. [Google Scholar] [CrossRef] [PubMed]
- Veering, B.; Cousins, M. Cardiovascular and pulmonary effects of epidural anaesthesia. Anaesth. Intensive Care 2000, 28, 620–635. [Google Scholar] [CrossRef] [PubMed]
- Kawasaki, T.; Ogata, M.; Kawasaki, C.; Okamot, K.; Sata, T. Effects of epidural anaesthesia on surgical stress-induced immunosuppression during upper abdominal surgery. Br. J. Anaesth. 2007, 98, 196–203. [Google Scholar] [CrossRef] [PubMed]
- Grandhi, R.K.; Lee, S.; Abd-Elsayed, A. The Relationship Between Regional Anesthesia and Cancer: A Metaanalysis. Ochsner J. 2017, 17, 345–361. [Google Scholar] [PubMed] [PubMed Central]
- Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. PLoS Med. 2009, 6, e1000097. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- WebPlotDigitizer. 2011. Available online: https://automeris.io (accessed on 12 May 2025).
- Sharma, D.; Ulaganathan, S.P.; Sharma, V.; Piplani, S.; Niraj, R.R.K. Deep Meta Tool: GUI tool to obtain Mean and Standard Deviation (SD) from Median and Interquartile range (IQR). Research Square 2021. [Google Scholar] [CrossRef]
- Sterne, J.; Savović, J.; Page, M.; Elbers, R.; Blencowe, N.; Boutron, I.; Cates, C.; Cheng, H.; MS, C.; SM, E.; et al. RoB 2: A revised tool for assessing risk of bias in randomised trials. BMJ (Clin. Res. Ed.) 2019, 366, l4898. [Google Scholar] [CrossRef] [PubMed]
- Suurmond, R.; van Rhee, H.; Hak, T. Introduction, comparison, and validation of Meta-Essentials: A free and simple tool for meta-analysis. Res. Synth. Methods 2017, 8, 537–553. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Caputo, M.; Alwair, H.; Rogers, C.A.; Ginty, M.; Monk, C.; Tomkins, S.; Mokhtari, A.; Angelini, G.D. Myocardial, inflammatory, and stress responses in off-pump coronary artery bypass graft surgery with thoracic epidural anesthesia. Ann. Thorac. Surg. 2009, 87, 1119–1126. [Google Scholar] [CrossRef] [PubMed]
- Cong, X.; Zhang, W.; Huang, Z.; Zhang, L.; Sun, M.; Chang, E.; Zhang, J. Effects of Different Anaesthesia Methods on Perioperative Cellular Immune Function and Longterm Outcomes in Patients Undergoing Radical Resection of Esophageal Cancer: A Prospective Cohort Study. Anesthesiol. Pain Med. 2020; epub ahead of print. [Google Scholar] [CrossRef]
- Duque, P.; Garutti, I.; Terradillos, E.; Ledesma, B.; Rancan, L.; Simon, C.; Vara, E. Modulation of CCL2 Expression by Laparoscopic Versus Open Surgery for Colorectal Cancer Surgery. Surg. Laparosc. Endosc. Percutan. Tech. 2019, 29, 101–108. [Google Scholar] [CrossRef] [PubMed]
- Elsayed, A.A.; Ei-deen, N.M.G.; Shams, G.H.R.; Aly, A.E.A.-e.; Mohammed, W.S. Comparative Study between General Anesthesia versus General Anesthesia Combined with Thoracic Epidural Analgesia on Cytokine Response in Laparoscopic Cholecystectomy Patients. Open J. Anesthesiol. 2020, 10, 247–262. [Google Scholar] [CrossRef]
- Fant, F.; Tina, E.; Sandblom, D.; Andersson, S.O.; Magnuson, A.; Hultgren-Hörnkvist, E.; Axelsson, K.; Gupta, A. Thoracic epidural analgesia inhibits the neuro-hormonal but not the acute inflammatory stress response after radical retropubic prostatectomy. Br. J. Anaesth. 2013, 110, 747–757. [Google Scholar] [CrossRef] [PubMed]
- Fares, K.M.; Mohamed, S.A.; Hamza, H.M.; Sayed, D.M.; Hetta, D.F. Effect of Thoracic Epidural Analgesia on Proinflammatory Cytokines in Patients Subjected to Protective Lung Ventilation During Ivor Lewis Esophagectomy. Pain Physician 2014, 17, 305–315. [Google Scholar]
- Gu, C.Y.; Zhang, J.; Qian, Y.N.; Tang, Q.F. Effects of epidural anesthesia and postoperative epidural analgesia on immune function in esophageal carcinoma patients undergoing thoracic surgery. Mol. Clin. Oncol. 2015, 3, 190–196. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Hadimioglu, N.; Ulugol, H.; Akbas, H.; Coskunfirat, N.; Ertug, Z.; Dinckan, A. Combination of epidural anesthesia and general anesthesia attenuates stress response to renal transplantation surgery. Transpl. Proc 2012, 44, 2949–2954. [Google Scholar] [CrossRef] [PubMed]
- Hou, B.J.; Du, Y.; Gu, S.X.; Fan, J.; Wang, R.; Deng, H.; Guo, D.X.; Wang, L.; Wang, Y.Y. General anesthesia combined with epidural anesthesia maintaining appropriate anesthesia depth may protect excessive production of inflammatory cytokines and stress hormones in colon cancer patients during and after surgery. Medicine 2019, 98, e16610. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Liu, W.; Wu, L.; Zhang, M.; Zhao, L. Effects of general anesthesia with combined epidural anesthesia on inflammatory response in patients with early-stage gastric cancer undergoing tumor resection. Exp. Ther. Med. 2019, 17, 35–40. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Moselli, N.M.; Baricocchi, E.; Ribero, D.; Sottile, A.; Suita, L.; Debernardi, F. Intraoperative epidural analgesia prevents the early proinflammatory response to surgical trauma. Results from a prospective randomized clinical trial of intraoperative epidural versus general analgesia. Ann. Surg. Oncol. 2011, 18, 2722–2731. [Google Scholar] [CrossRef] [PubMed]
- Pi, J.; Sun, Y.; Zhang, Z.; Wan, C. Combined anesthesia shows better curative effect and less perioperative neuroendocrine disorder than general anesthesia in early stage NSCLC patients. J. Int. Med. Res. 2019, 47, 4743–4752. [Google Scholar] [CrossRef] [PubMed]
- Sidiropoulou, I.; Tsaousi, G.G.; Pourzitaki, C.; Logotheti, H.; Tsantilas, D.; Vasilakos, D.G. Impact of anesthetic technique on the stress response elicited by laparoscopic cholecystectomy: A randomized trial. J. Anesth. 2016, 30, 522–525. [Google Scholar] [CrossRef] [PubMed]
- Sun, H.Z.; Song, Y.L.; Wang, X.Y. Effects of Different Anesthetic Methods on Cellular Immune and Neuroendocrine Functions in Patients With Hepatocellular Carcinoma Before and After Surgery. J. Clin. Lab. Anal. 2016, 30, 1175–1182. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Tan, W.F.; Guo, B.; Ma, H.; Li, X.Q.; Fang, B.; Lv, H.W. Changes in postoperative night bispectral index of patients undergoing thoracic surgery with different types of anaesthesia management: A randomized controlled trial. Clin. Exp. Pharmacol. Physiol. 2016, 43, 304–311. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Liang, S.; Chen, H.; Xu, Y.; Wang, Y. The effects of epidural anaesthesia and analgesia on T lymphocytes differentiation markers and cytokines in patients after gastric cancer resection. BMC Anesth. 2019, 19, 102. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Xu, Y.J.; Chen, W.K.; Zhu, Y.; Wang, S.L.; Miao, C.H. Effect of thoracic epidural anaesthesia on serum vascular endothelial growth factor C and cytokines in patients undergoing anaesthesia and surgery for colon cancer. Br. J. Anaesth. 2014, 113, i49–i55. [Google Scholar] [CrossRef]
- Xu, Y.J.; Sun, X.; Jiang, H.; Yin, Y.H.; Weng, M.L.; Sun, Z.R.; Chen, W.K.; Miao, C.H. Randomized clinical trial of continuous transversus abdominis plane block, epidural or patient-controlled analgesia for patients undergoing laparoscopic colorectal cancer surgery. Br. J. Surg. 2020, 107, e133–e141. [Google Scholar] [CrossRef] [PubMed]
- Yan, W.; Mao, H.; Qiu, P. Effects of different analgesia regimens on early post-operative cognitive dysfunction in elderly patients undergoing radical resection of cervical carcinoma. Exp. Ther. Med. 2019, 18, 1465–1469. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Yokoyama, M.; Itano, Y.; Katayama, H.; Morimatsu, H.; Takeda, Y.; Takahashi, T.; Nagano, O.; Morita, K. The effects of continuous epidural anesthesia and analgesia on stress response and immune function in patients undergoing radical esophagectomy. Anesth. Analg. 2005, 101, 1521–1527. [Google Scholar] [CrossRef] [PubMed]
- Okuda, J.; Suzuki, T.; Wakaizumi, K.; Kato, J.; Yamada, T.; Morisaki, H. Effects of Thoracic Epidural Anesthesia on Systemic and Local Inflammatory Responses in Patients Undergoing Lung Cancer Surgery: A Randomized Controlled Trial. J. Cardiothorac. Vasc. Anesth. 2022, 36, 1380–1386. [Google Scholar] [CrossRef] [PubMed]
- Engelman, R.M.; Rousou, J.A.; Flack, J.E., 3rd; Deaton, D.W.; Humphrey, C.B.; Ellison, L.H.; Allmendinger, P.D.; Owen, S.G.; Pekow, P.S. Fast-track recovery of the coronary bypass patient. Ann. Thorac. Surg. 1994, 58, 1742–1746. [Google Scholar] [CrossRef] [PubMed]
- Block, B.; Liu, S.; Rowlingson, A.; Cowan, A.; Cowan, J.; Wu, C. Efficacy of postoperative epidural analgesia: A meta-analysis. JAMA 2003, 290, 2455–2463. [Google Scholar] [CrossRef] [PubMed]
- Beattie, W.; Badner, N.; Choi, P. Epidural analgesia reduces postoperative myocardial infarction: A meta-analysis. Anesth. Analg. 2001, 93, 853–858. [Google Scholar] [CrossRef] [PubMed]
- Diez-Ruiz, A.; Tilz, G.P.; Zangerle, R.; Baier-Bitterlich, G.; Wachter, H.; Fuchs, D. Soluble receptors for tumour necrosis factor in clinical laboratory diagnosis. Eur. J. Haematol. 1995, 54, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Tanabe, K.; Matsushima-Nishiwaki, R.; Yamaguchi, S.; Iida, H.; Dohi, S.; Kozawa, O. Mechanisms of tumor necrosis factor-alpha-induced interleukin-6 synthesis in glioma cells. J. Neuroinflamm. 2010, 7, 16. [Google Scholar] [CrossRef] [PubMed]
- Tanaka, T.; Narazaki, M.; Kishimoto, T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb. Perspect. Biol. 2014, 6, a016295. [Google Scholar] [CrossRef] [PubMed]
- Kuribayashi, T. Elimination half-lives of interleukin-6 and cytokine-induced neutrophil chemoattractant-1 synthesized in response to inflammatory stimulation in rats. Lab. Anim. Res. 2018, 34, 80–83. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
- Szczepanik, A.; Scislo, L.; Scully, T.; Walewska, E.; Siedlar, M.; Kolodziejczyk, P.; Lenart, M.; Rutkowska, M.; Galas, A.; Czupryna, A.; et al. IL-6 serum levels predict postoperative morbidity in gastric cancer patients. Gastric Cancer Off. J. Int. Gastric Cancer Assoc. Jpn. Gastric Cancer Assoc. 2011, 14, 266–273. [Google Scholar] [CrossRef] [PubMed]
- Straatman, J.; Cuesta, M.; Tuynman, J.; Veenhof, A.; Bemelman, W.; van der Peet, D. C-reactive protein in predicting major postoperative complications are there differences in open and minimally invasive colorectal surgery? Substudy from a randomized clinical trial. Surg. Endosc. 2018, 32, 2877–2885. [Google Scholar] [CrossRef] [PubMed]
- Tomlinson, J.W.; Walker, E.A.; Bujalska, I.J.; Draper, N.; Lavery, G.G.; Cooper, M.S.; Hewison, M.; Stewart, P.M. 11beta-hydroxysteroid dehydrogenase type 1: A tissue-specific regulator of glucocorticoid response. Endocr. Rev. 2004, 25, 831–866. [Google Scholar] [CrossRef] [PubMed]
- Silverman, M.N.; Sternberg, E.M. Glucocorticoid regulation of inflammation and its functional correlates: From HPA axis to glucocorticoid receptor dysfunction. Ann. N. Y. Acad. Sci. 2012, 1261, 55–63. [Google Scholar] [CrossRef] [PubMed]
- Mu, D.L.; Li, L.H.; Wang, D.X.; Li, N.; Shan, G.J.; Li, J.; Yu, Q.J.; Shi, C.X. High postoperative serum cortisol level is associated with increased risk of cognitive dysfunction early after coronary artery bypass graft surgery: A prospective cohort study. PLoS ONE 2013, 8, e77637. [Google Scholar] [CrossRef] [PubMed]
- Shintani, Y.; Ito, T.; Fields, L.; Shiraishi, M.; Ichihara, Y.; Sato, N.; Podaru, M.; Kainuma, S.; Tanaka, H.; Suzuki, K. IL-4 as a Repurposed Biological Drug for Myocardial Infarction through Augmentation of Reparative Cardiac Macrophages: Proof-of-Concept Data in Mice. Sci. Rep. 2017, 7, 6877. [Google Scholar] [CrossRef] [PubMed]
- Mitchell, R.; Hassan, M.; Burton, B.; Britton, G.; Hill, E.; Verhagen, J.; Wraith, D. IL-4 enhances IL-10 production in Th1 cells: Implications for Th1 and Th2 regulation. Sci. Rep. 2017, 7, 11315. [Google Scholar] [CrossRef] [PubMed]
- Mosser, D.; Zhang, X. Interleukin-10: New perspectives on an old cytokine. Immunol. Rev. 2008, 226, 205–218. [Google Scholar] [CrossRef] [PubMed]
- Salmon-Eh, R.V.; Ramont, L.; Godeau, G.; Birembaut, P.; Guenounou, M.; Bernard, P.; Maquart, F. Implication of interleukin-4 in wound healing. Lab. Investig. A J. Tech. Methods Pathol. 2000, 80, 1337–1343. [Google Scholar] [CrossRef] [PubMed]
- King, A.; Balaji, S.; Le, L.; Crombleholme, T.; Keswani, S. Regenerative Wound Healing: The Role of Interleukin-10. Adv. Wound Care 2014, 3, 315–323. [Google Scholar] [CrossRef] [PubMed]
- Yap, A.; Lopez-Olivo, M.A.; Dubowitz, J.; Hiller, J.; Riedel, B. Anesthetic technique and cancer outcomes: A meta-analysis of total intravenous versus volatile anesthesia. Can. J. Anaesth. = J. Can. D’anesth. 2019, 66, 546–561. [Google Scholar] [CrossRef] [PubMed]
- Li, R.; Huang, Y.; Lin, J. Distinct effects of general anesthetics on lung metastasis mediated by IL-6/JAK/STAT3 pathway in mouse models. Nat. Commun. 2020, 11, 642. [Google Scholar] [CrossRef]
- Yu, G.; Tang, B.; Yu, P.; Peng, Z.; Qian, F.; Sun, G. Systemic and peritoneal inflammatory response after laparoscopic-assisted gastrectomy and the effect of inflammatory cytokines on adhesion of gastric cancer cells to peritoneal mesothelial cells. Surg. Endosc. 2010, 24, 2860–2870. [Google Scholar] [CrossRef] [PubMed]
- Arimoto, A.; Yamashita, K.; Hasegawa, H.; Sugita, Y.; Fukuoka, E.; Tanaka, T.; Suzuki, S.; Kakeji, Y. Immunosuppression Induced by Perioperative Peritonitis Promotes Lung Metastasis. Anticancer Res. 2018, 38, 4333–4338. [Google Scholar] [CrossRef] [PubMed]
- Tsukamoto, H.; Fujieda, K.; Senju, S.; Ikeda, T.; Oshiumi, H.; Nishimura, Y. Immune-suppressive effects of interleukin-6 on T-cell-mediated anti-tumor immunity. Cancer Sci. 2018, 109, 523–530. [Google Scholar] [CrossRef] [PubMed]
- Tohme, S.; Simmons, R.L.; Tsung, A. Surgery for Cancer: A Trigger for Metastases. Cancer Res. 2017, 77, 1548–1552. [Google Scholar] [CrossRef] [PubMed] [PubMed Central]
Study ID | Methods | Participants | Interventions | TEA Procedure | Surgery Duration (Min with SD or Range) | Outcomes | |
---|---|---|---|---|---|---|---|
TEA + GA | GA | ||||||
Caputo 2009 [22] | RCT, observer blinded | 74 adults undergoing off-pump coronary artery bypass graft surgery | T 2/3 or T 3/4 epidural plus GA vs. GA alone | Perioperative, initial bolus of 5 mL bupivacaine 0.5% + 5 mL bolus followed by continuous infusion of 0.125% bupivacaine and 0.0003% clonidine at rate of 10 mL/h. Postoperative, top-up bolus doses 4 mL 0.25% bupivacaine for 72 h | 248 (255–528) | 361 (290–540) | troponin I, 8-isoprostane, cortisol, C3alpha, IL-6, IL-8, and IL-10 |
Cong 2020 [23] | RCT | 120 adults undergoing radical resection of esophageal cancer | T 6/7 epidural + GA vs. PVB + GA vs. GA alone | Epidural catheter with 10 mL 0.375% ropivacaine | 847 (306) | 1102 (450) | IL-6, IL-4, TNF-α, IFN-γ, CD3+, CD4+, CD8+, CD4+/CD8+ |
Duque 2019 [24] | RCT, patients and observer blinded | 39 adults scheduled for colorectal cancer surgery | T 7–10 epidural + GA vs. GA alone | Perioperative, initial dose of 0.5% bupivacaine 8–12 mL followed by continuous infusion of 0.5% bupivacaine at 7–10 mL/h. Postoperative, patient-controlled epidural infusions of 0.125% bupivacaine at 7–10 mL/h with additional boluses of 7 mL of same solution, with max of 2 boluses/h. | 186 (58) | 183.4 (79) | CPR, Cortisol, CCL2, TNF-α, IL-1, IL-2, IL-4, IL-6, IL-8, Nitric oxide, VEGF, MMP-3, Leucocytes, and Lymphocytes |
Elsayed 2020 [25] | RCT | 40 adults undergoing laparoscopic cholecystectomy | T 8/9 epidural + GA vs. GA alone | Epidural catheter with a bolus dose of 6–8 mL of 0.25% bupivacaine and 50 μg fentanyl. Continuous epidural infusion with 0.125% bupivacaine and fentanyl 1.5 μg/mL at 0.1 mL/kg/h. | 68 (9.89) | 74 (11.88) | IL-6, IL-8 |
Fant 2013 [26] | RCT, observer blinded | 26 adults undergoing elective radical retropubic prostatectomy | T 10–12 epidural + GA vs. GA alone | Perioperative, epidural catheter with a bolus dose of 2–3 mL 0.5% bupivacaine with epinephrine followed by a continuous infusion of bupivacaine 0.5% at 2–4 mL/h | 100 (27) | 109 (30) | CRP, cortisol, IL-6, TNF-alpha, IFN-gamma, IL-2, IL-12p70, IL-17, IL-4, IL-10, |
Fares 2014 [27] | RCT, observer blinded | 30 adults scheduled for elective Ivor Lewis esophagectomy | TEA + GA vs. GA alone | Perioperative, initial dose of 0.1 mL/kg of 0.125% bupivacaine + fentanyl 15 μL/mL followed by continuous infusion of 0.1 mL/kg/h of 0.125% bupivacaine + fentanyl 10 μL/mL. Postoperative, continuous infusion of 0.1 mg/kg/h of 0.125% bupivacaine + fentanyl 5 μg/mL for 72 h. | 270.7 (20.4) | 269 (20.9) | IL-6, IL-8 |
Gu 2015 [28] | RCT | 29 esophageal carcinoma patients undergoing thoracic surgery | T 7/8 epidural + GA vs. GA alone | Perioperative, continues infusion of 0.25% ropivacaine at 5–7 mL/h. Postoperative, continuous infusion of 0.125% ropivacaine + fentanyl 2 μL/mL at initial 10 mL followed by 5 mL. | 167.6 (14.5) | 164.8 (13.2) | cortisol, IL-6, IFN-γ, IL-4, IL-17 |
Hadimioglu 2012 [29] | RCT, observer blinded | 46 adults scheduled for renal transplantation surgery | L1/2 epidural + GA vs. GA alone | Epidural: 0.5% bupivacaine (14–18 mL). Patient-controlled analgesia with morphine: 1 mg of loading dose, 0.5 mg/h basal infusion, 1 mg bolus doses with 20 min lock-out interval | 102.1 (25.2) | 100.9 (15.2) | TNF-α, IL-6, adiponectin, resistin |
Hou 2019 [30] | RCT, observer blinded | 120 adults undergoing colon cancer surgery | T 10/11 epidural + GA vs. GA alone | initial dose of 8 mL 0.375% bupivacaine followed by 4 mL bupivacaine/50 min | TNF-α, IL-6, IL-10, crotisol, adrenocorticotropic hormone, endothelin-1 | ||
Liu 2019 [31] | RCT, observer blinded | 107 adults with early-stage gastric cancer undergoing tumor resection | T 8–10 epidural + GA vs. GA alone | Perioperative, epidural administration of 1% lidocaine (5–10 mL) and 0.375% ropivacaine using micropump (5–8 mL/h). Postoperative, injected 0.12% ropivacaine and 0.2 μg/mL sufentanil at rate of 5 mL/h, performed for 2–6 days. | 205.02 (52.22) | 211.72 (44.34) | CD4+ cell, CD8+ cell, IL-1, CRP, TNF-α, IL-8 |
Moselli 2011 [32] | RCT, observer blinded | 35 adults undergoing major surgery for colon cancer | T 9/10 or T 12/L1 epidural + GA vs. GA alone | Initial dose of 5–7 μg of sufentanil in fractioned boli and 0.5% L-bupivacaine 7–9 mL/h in continuous infusion started 40 min before skin incision followed by continuous epidural infusion of 0.5% L-bupivacaine 3–5 mL/h. | 243.8 (88.3) | 216.5 (105.3) | IL-4, IL-10, IL-6 |
Pi 2019 [33] | RCT, observer blinded | 149 adults with early-stage non-small cell lung carcinoma undergoing tumor resection | T 8–T 10 epidural + GA vs. GA alone | Epidural administration of 1% lidocaine (5–10 mL) and 0.375% ropivacaine using a micropump at rate of 5–8 mL/h. | 219.02 (45.46) | 217.72 (36.65) | IL-1, IL-8, CRP, TNF-α |
Sidiropoulou 2016 [34] | RCT, patients and observer blinded | 60 adults scheduled to undergo elective laparoscopic cholecystectomy | T 12–L2 epidural + GA vs. GA alone | Epidural catheter with a bolus dose of ropivacaine 1% 15 mL | 64.1 (11.8) | 65.2 (16.3) | CRP, cortisol |
Sun 2016 [35] | RCT, observer blinded | 72 adults with hepatocellular carcinoma undergoing hepatectomy | T 8/9 epidural + GA vs. GA alone | Epidural with 1% lidocaine 5 mL/h | 152.81 (13.37) | 154.86 (13.63) | cortisol, CD3+, CD4+ T cell, IL-6, IL-10, IFN-γ |
Tan 2016 [36] | RCT, observer blinded | 106 adults undergoing lobectomy or pneumonectomy for lung cancer | T 5–7 epidural + GA vs. GA + dexmedetomidine vs. GA alone | Initial dose of 8–10 mL 0.25% ropivacaine followed by 0.15% ropivacaine and 1.79 μg/mL fentanyl at 5 mL/h and bolus dose of 6 mL without 40 min lockout time. | IL-6, TNF-α | ||
Wang 2019 [37] | RCT, observer blinded | 40 adults undergoing radical resection of gastric cancer | T 8–T 10 epidural + GA vs. GA alone | Initial dose 0.5% ropivacaine, 5–7 mL followed by 0.2% ropivacaine and 0.5 microg/mL sufentanil was available for 72–120 h | 135 (120, 210) | 135 (120, 225) | CD3+ cell, CD4+, CD8+, IL-4, IL-6, IFN-γ |
Xu 2014 [38] | RCT, observer blinded | 40 adults undergoing open colon cancer surgery | T 9–T 12 epidural + GA vs. GA alone | Perioperative, initial dose of 0.375% ropivacaine was 6–8 mL followed by continues infusion of ropivacaine at 5 mL/h. Postoperative, continuous infusion of 4 mL/h 0.15% ropivacaine and 0.5 μg/mL sufentanil and 2 mL bolus on request | 102 (29) | 118 (38) | VEGF-C, TGF-β, IL-6, IL-10 |
Xu 2020 [39] | RCT, observer blinded | 110 adults undergoing laparoscopic colorectal cancer surgery | T 9–T 12 epidural + GA vs. GA alone vs. GA + TAP block | Perioperative, initial dose of 6–8 mL 0.25% ropivacaine followed by continuous infusion rate of 5 mL/h. Postoperative, 0.15% ropivacaine and 0.5 μg/mL sufentanil at continuous infusion rate of 4 mL/h | 132.2 (19.6) | 131.0 (20.2) | VEGF-C, IL-6, adrenaline, cortisol |
Yan 2019 [40] | RCT, observer blinded | 74 adults undergoing radical resection of cervical carcinoma | L2/3 epidural + GA vs. GA alone | Perioperative, infused 10 mL 0.75% ropivacaine. Postoperative, 0.125% ropivacaine; background dose, 8 mL/h; PCA dose, 2 mL/time, at 20 min intervals | 145.6 (13.5) | 151.3 (14.8) | CRP, IL-6, neutrophils |
Yokoyama 2005 [41] | RCT, observer blinded | 30 adults undergoing radical esophagectomy | T 3/4 plus T 10/11 epidural + GA vs. GA alone | Perioperative, epidural catheters with 8 mL 1.5% lidocaine. Postoperative, 1% lidocaine with 4 μg/mL fentanyl at 6 mL/h | 616 (69) | 648 (66) | epinephrine, norepinephrine, cortisol, ACTH, IL-1, IL-6, IL-10, TNF-α, B cells, T cells, NK cells, CRP |
Okuda 2022 [42] | RCT, patients and observer blinded | 60 adults undergo lung cancer surgery | Th5/Th8 epidural + GA vs. GA alone | Perioperative, initial dose of 5–15 mL 0.25% levobupivacaine followed by continuous infusion at the rate of 3–10 mL/h. Postoperative, 5–10 mL 0.25% levobupivacaine with patient-controlled epidural analgesia in both groups | 121 (40) | 121 (38) | IL-6, TNF-α, IL-10, MDA |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Lin, E.J.; Prost, S.; Lin, H.J.; Shah, S.; Li, R. Combined General/Epidural Anesthesia vs. General Anesthesia on Postoperative Cytokines: A Review and Meta-Analysis. Cancers 2025, 17, 1667. https://doi.org/10.3390/cancers17101667
Lin EJ, Prost S, Lin HJ, Shah S, Li R. Combined General/Epidural Anesthesia vs. General Anesthesia on Postoperative Cytokines: A Review and Meta-Analysis. Cancers. 2025; 17(10):1667. https://doi.org/10.3390/cancers17101667
Chicago/Turabian StyleLin, Erica J., Stephen Prost, Hannah J. Lin, Syed Shah, and Ru Li. 2025. "Combined General/Epidural Anesthesia vs. General Anesthesia on Postoperative Cytokines: A Review and Meta-Analysis" Cancers 17, no. 10: 1667. https://doi.org/10.3390/cancers17101667
APA StyleLin, E. J., Prost, S., Lin, H. J., Shah, S., & Li, R. (2025). Combined General/Epidural Anesthesia vs. General Anesthesia on Postoperative Cytokines: A Review and Meta-Analysis. Cancers, 17(10), 1667. https://doi.org/10.3390/cancers17101667