Preoperative Treatment with Dexamethasone and Etoricoxib: A Comparison of Effects on Serum Interleukin-6 (IL-6) Levels and Postoperative Delirium (POD) in Geriatric Patients with General Anesthesia
-
Akbar Hasyim
,
Syafruddin Gaus
,
Nur Surya Wirawan
,
Andi Salahuddin
,
Andi Muhammad Takdir Musba
,
Andi Adil
Abstract
Introduction: In geriatrics, general anesthesia can cause a high incidence of post-operative delirium (POD), reaching 3-61%, characterized by elevated interleukin-6 (IL-6) levels. Dexamethasone is often used as an adjunct in anesthesia to reduce cognitive impairment, but it can cause psychiatric symptoms. Cyclooxygenase-2 inhibitors such as parecoxib have been reported to inhibit post-surgical inflammation levels and improve neurological and neurocognitive disorders. However, there are no reports on the use of etoricoxib and its comparison with dexamethasone for these effects.
Objective: To analyze the comparison between preoperative administration of dexamethasone and etoricoxib on IL-6 levels and POD in geriatric patients with general anesthesia.
Methods: This Randomized single-blind clinical trial study included 36 geriatric patients undergoing elective surgery who received therapy under general anesthesia were randomly divided into three groups: placebo (group P, n = 12), dexamethasone 10 mg (group D, n = 12), and etoricoxib 90 mg (group E, n = 12). IL-6 levels were measured preoperatively, 6 hours, and 24 hours postoperatively using the ELISA method. POD was measured using the Confusion Assessment Method (CAM) both preoperatively and 24 hours postoperatively.
Results: The incidence of POD at 24 hours postoperatively was significantly lower in group E compared to groups P and D (p < 0.05). Changes in IL-6 levels at 6 hours and 24 hours postoperatively were significantly lower in group E compared to groups P and D (p < 0.05). There was a significant relationship between IL-6 levels at 6 hours postoperatively and CAM (r = 0.481; p < 0.05), and there was a significant relationship between IL-6 levels at 24 hours postoperatively and CAM (r = 0.537; p < 0.05).
Conclusion: Preoperative treatment etoricoxib was more effective in suppressing IL-6 levels and the incidence of POD than dexamethasone and placebo.
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[2] Staicu RE, Vernic C, Ciurescu S, Lascu A, Aburel OM, Deutsch P, et al. Postoperative Delirium and Cognitive Dysfunction After Cardiac Surgery: The Role of Inflammation and Clinical Risk Factors. Diagnostics (Basel). 2025; 15(7):844.
[3] Travica N, Lotfaliany M, Marriott A, Safavynia SA, Lane MM, Gray L, et al. Peri-Operative Risk Factors Associated with Post-Operative Cognitive Dysfunction (POCD): An Umbrella Review of Meta-Analyses of Observational Studies. J Clin Med. 2023; 12(4):1610.
[4] Wittmann M, Kirfel A, Jossen D, Mayr A, Menzenbach J. The Impact of Perioperative and Predisposing Risk Factors on the Development of Postoperative Delirium and a Possible Gender Difference. Geriatrics (Basel). 2022; 7(3):65.
[5] Borchers F, Rumpel M, Laubrock J, Spies C, Kozma P, Slooter A, et al. Cognitive reserve and the risk of postoperative neurocognitive disorders in older age. Front Aging Neurosci. 2024; 15:1327388.
[6] Wu Y, Yu C, Gao F. Risk factors for postoperative cognitive dysfunction in elderly patients undergoing surgery for oral malignancies. Perioper Med (Lond). 2023; 12(1):42.
[7] Jin R, Chan AKY, Wu J, Lee TMC. Relationships between Inflammation and Age-Related Neurocognitive Changes. Int J Mol Sci. 2022; 23(20):12573.
[8] Almuzayyen HA, Chowdhury T, Alghamdi AS. Postoperative cognitive recovery and prevention of postoperative cognitive complications in the elderly patient. Saudi J Anaesth. 2023; 17(4):550-6.
[9] Yang X, Huang X, Li M, Jiang Y, Zhang H. Identification of individuals at risk for postoperative cognitive dysfunction (POCD). Ther Adv Neurol Disord. 2022; 15:17562864221114356.
[10] Rengel KF, Boncyk CS, DiNizo D, Hughes CG. Perioperative Neurocognitive Disorders in Adults Requiring Cardiac Surgery: Screening, Prevention, and Management. Semin Cardiothorac Vasc Anesth. 2023; 27(1):25-41.
[11] Valentin LS, Pereira VF, Pietrobon RS, Schmidt AP, Oses JP, Portela LV, et al. Effects of Single Low Dose of Dexamethasone before Noncardiac and Nonneurologic Surgery and General Anesthesia on Postoperative Cognitive Dysfunction-A Phase III Double Blind, Randomized Clinical Trial. PLoS One. 2016; 11(5):e0152308.
[12] Huang JW, Yang YF, Gao XS, Xu ZH. A single preoperative low-dose dexamethasone may reduce the incidence and severity of postoperative delirium in the geriatric intertrochanteric fracture patients with internal fixation surgery: an exploratory analysis of a randomized, placebo-controlled trial. J Orthop Surg Res. 2023; 18(1):441.
[13] Wu Z, Li H, Liao K, Wang Y. Association between dexamethasone and delirium in critically ill patients: a retrospective cohort study of a large clinical database. J Surg Res. 2021; 263:89-101.
[14] Jorna LS, Spikman JM, Schoemaker R, van Leeuwen B, Sommer IE. The efficacy of anti-inflammatory medication in postoperative cognitive decline: a meta-analysis. J Neurol Neurosci. 2020; 11(3):1-1.
[15] Birmingham B, Buvanendran A. Nonsteroidal anti-inflammatory drugs, acetaminophen, and COX-2 inhibitors. Pract Manage Pain. Elsevier Inc. 2013:553-68.e5.
[16] Sil S, Ghosh T. Etoricoxib inhibits peripheral inflammation and alters immune responses in intracerebroventricular colchicine injected rats. J Neuroimmunol. 2018; 317:15-23.
[17] Renner B, Zacher J, Buvanendran A, Walter G, Strauss J, Brune K. Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery--a pilot study. Naunyn Schmiedebergs Arch Pharmacol. 2010; 381(2):127-36.
[18] Yin WY, Peng T, Guo BC, Fan CC, Xu J, Liu XM, et al. Effects of parecoxib on postoperative cognitive dysfunction and serum levels of NSE and S100$\beta$ in elderly patients undergoing surgery. Eur Rev Med Pharmacol Sci. 2024; 28(1):278-87.
[19] Laishram K, Borgohain B, Laishram A, Khonglah TG, Ruram AA, Debbarma S. Serum IL-6 as a Surrogate Biomarker of Post-operative Complications in Invasive Orthopaedic Surgeries: A Prospective Observational Study. Indian J Orthop. 2024; 58(8):1153-8.
[20] Lv XC, Lin Y, Wu QS, Wang L, Hou YT, Dong Y, et al. Plasma interleukin-6 is a potential predictive biomarker for postoperative delirium among acute type a aortic dissection patients treated with open surgical repair. J Cardiothorac Surg. 2021; 16(1):146.
[21] Safavynia SA, Goldstein PA. The Role of Neuroinflammation in Postoperative Cognitive Dysfunction: Moving From Hypothesis to Treatment. Front Psychiatry. 2019; 9:752.
[22] Theodoridou A, Gika H, Diza E, Garyfallos A, Settas L. In vivo study of pro-inflammatory cytokine changes in serum and synovial fluid during treatment with celecoxib and etoricoxib and correlation with VAS pain change and synovial membrane penetration index in patients with inflammatory arthritis. Mediterr J Rheumatol. 2017; 28(1):33-40.
[23] Shieh JM, Tsai YJ, Ma MC, Chen CL, Wu WB. The cyclooxygenase-2 upregulation mediates production of PGE2 autacoid to positively regulate interleukin-6 secretion in chronic rhinosinusitis with nasal polyps and polyp-derived fibroblasts. Sci Rep. 2024; 14(1):7559.
[24] Zhang S, Tao XJ, Ding S, Feng XW, Wu FQ, Wu Y. Associations between postoperative cognitive dysfunction, serum interleukin-6 and postoperative delirium among patients after coronary artery bypass grafting: a mediation analysis. Nurs Crit Care. 2024; 29(6):1245-52.
[25] Li YC, Xi CH, An YF, Dong WH, Zhou M. Perioperative inflammatory response and protein S-100$\beta$ concentrations - relationship with post-operative cognitive dysfunction in elderly patients. Acta Anaesthesiol Scand. 2012; 56(5):595-600.
[26] Huang X, Li L, Feng Q. Correlation Analysis of Inflammatory Markers CRP and IL-6 and Postoperative Delirium (POD) in Elderly Patients: A Meta-Analysis of Observational Studies. J Environ Public Health. 2022; 2022:1136386.
[27] Song Y, Luo Y, Zhang F, Ma Y, Lou J, Li H, et al. Systemic immune-inflammation index predicts postoperative delirium in elderly patients after surgery: a retrospective cohort study. BMC Geriatr. 2022; 22(1):730.
[28] Tan XX, Qiu LL, Sun J. Research Progress on the Role of Inflammatory Mechanisms in the Development of Postoperative Cognitive Dysfunction. Biomed Res Int. 2021; 2021:3883204.
[29] Xue YH, Peng YS, Ting HF, Peijer Hsieh J, Huang YK, Wang YH, et al. Etoricoxib and Diclofenac Might Reduce the Risk of Dementia in Patients with Osteoarthritis: A Nation-Wide, Population-Based Retrospective Cohort Study. Dement Geriatr Cogn Disord. 2018; 45(5-6):262-71.
[30] Mohan P, Sharma AK, Sinha S, Sabarad R. An experimental study of rosuvastatin's analgesic effect and its interaction with etoricoxib, tramadol, amlodipine, and amitriptytline in albino mice. Med J Armed Forces India. 2022; 78 Suppl 1:S61-8.
[31] Singh MK, Kumar S, Dixit P, Singh V, Verma S, Singh GP. The effect of celecoxib on early postoperative cognitive dysfunction in elderly patients of fracture neck of femur: a prospective randomised double-blind study. Anaesth Pain Intensive Care. 2021; 25(3):287-94.
[32] Khaled M, Sabac D, Fuda M, Koubaesh C, Gallab J, Qu M, et al. Postoperative pain and neurocognitive outcomes after noncardiac surgery: a systematic review and dose–response meta-analysis. Br J Anaesth. 2025; 134(1):89-101.
[33] Du Y, Cao J, Gao C, He K, Wang S. Influence of intraoperative pain management on postoperative delirium in elderly patients: A prospective single-center randomized controlled trial. Pain Ther. 2025; 14(1):387-400.
[34] La Rosa GR, Consoli M, Abiad RS, Toscano A, Pedullà E. Comparing pre-and postoperative etoricoxib administration versus only postoperative on third molar extraction sequelae and oral health quality of life: a prospective quasi-experimental study. Clin Oral Investig. 2024; 28(4):218.
[35] Lierz P, Losch H, Felleiter P. Evaluation of a single preoperative dose of etoricoxib for postoperative pain relief in therapeutic knee arthroscopy: a randomized trial. Acta Orthop. 2012; 83(6):642-7.
[36] Srivastava S, Gupta D, Naz A, Rizvi MM, Singh PK. Effects of preoperative single dose Etoricoxib on postoperative pain and sleep after lumbar diskectomy: prospective randomized double blind controlled study. Middle East J Anaesthesiol. 2012; 21(5):725-30.
[37] Shi H, Du X, Wu F, Hu Y, Xv Z, Mi W. Dexmedetomidine improves early postoperative neurocognitive disorder in elderly male patients undergoing thoracoscopic lobectomy. Exp Ther Med. 2020; 20(4):3868-77.
[2] Staicu RE, Vernic C, Ciurescu S, Lascu A, Aburel OM, Deutsch P, et al. Postoperative Delirium and Cognitive Dysfunction After Cardiac Surgery: The Role of Inflammation and Clinical Risk Factors. Diagnostics (Basel). 2025; 15(7):844.
[3] Travica N, Lotfaliany M, Marriott A, Safavynia SA, Lane MM, Gray L, et al. Peri-Operative Risk Factors Associated with Post-Operative Cognitive Dysfunction (POCD): An Umbrella Review of Meta-Analyses of Observational Studies. J Clin Med. 2023; 12(4):1610.
[4] Wittmann M, Kirfel A, Jossen D, Mayr A, Menzenbach J. The Impact of Perioperative and Predisposing Risk Factors on the Development of Postoperative Delirium and a Possible Gender Difference. Geriatrics (Basel). 2022; 7(3):65.
[5] Borchers F, Rumpel M, Laubrock J, Spies C, Kozma P, Slooter A, et al. Cognitive reserve and the risk of postoperative neurocognitive disorders in older age. Front Aging Neurosci. 2024; 15:1327388.
[6] Wu Y, Yu C, Gao F. Risk factors for postoperative cognitive dysfunction in elderly patients undergoing surgery for oral malignancies. Perioper Med (Lond). 2023; 12(1):42.
[7] Jin R, Chan AKY, Wu J, Lee TMC. Relationships between Inflammation and Age-Related Neurocognitive Changes. Int J Mol Sci. 2022; 23(20):12573.
[8] Almuzayyen HA, Chowdhury T, Alghamdi AS. Postoperative cognitive recovery and prevention of postoperative cognitive complications in the elderly patient. Saudi J Anaesth. 2023; 17(4):550-6.
[9] Yang X, Huang X, Li M, Jiang Y, Zhang H. Identification of individuals at risk for postoperative cognitive dysfunction (POCD). Ther Adv Neurol Disord. 2022; 15:17562864221114356.
[10] Rengel KF, Boncyk CS, DiNizo D, Hughes CG. Perioperative Neurocognitive Disorders in Adults Requiring Cardiac Surgery: Screening, Prevention, and Management. Semin Cardiothorac Vasc Anesth. 2023; 27(1):25-41.
[11] Valentin LS, Pereira VF, Pietrobon RS, Schmidt AP, Oses JP, Portela LV, et al. Effects of Single Low Dose of Dexamethasone before Noncardiac and Nonneurologic Surgery and General Anesthesia on Postoperative Cognitive Dysfunction-A Phase III Double Blind, Randomized Clinical Trial. PLoS One. 2016; 11(5):e0152308.
[12] Huang JW, Yang YF, Gao XS, Xu ZH. A single preoperative low-dose dexamethasone may reduce the incidence and severity of postoperative delirium in the geriatric intertrochanteric fracture patients with internal fixation surgery: an exploratory analysis of a randomized, placebo-controlled trial. J Orthop Surg Res. 2023; 18(1):441.
[13] Wu Z, Li H, Liao K, Wang Y. Association between dexamethasone and delirium in critically ill patients: a retrospective cohort study of a large clinical database. J Surg Res. 2021; 263:89-101.
[14] Jorna LS, Spikman JM, Schoemaker R, van Leeuwen B, Sommer IE. The efficacy of anti-inflammatory medication in postoperative cognitive decline: a meta-analysis. J Neurol Neurosci. 2020; 11(3):1-1.
[15] Birmingham B, Buvanendran A. Nonsteroidal anti-inflammatory drugs, acetaminophen, and COX-2 inhibitors. Pract Manage Pain. Elsevier Inc. 2013:553-68.e5.
[16] Sil S, Ghosh T. Etoricoxib inhibits peripheral inflammation and alters immune responses in intracerebroventricular colchicine injected rats. J Neuroimmunol. 2018; 317:15-23.
[17] Renner B, Zacher J, Buvanendran A, Walter G, Strauss J, Brune K. Absorption and distribution of etoricoxib in plasma, CSF, and wound tissue in patients following hip surgery--a pilot study. Naunyn Schmiedebergs Arch Pharmacol. 2010; 381(2):127-36.
[18] Yin WY, Peng T, Guo BC, Fan CC, Xu J, Liu XM, et al. Effects of parecoxib on postoperative cognitive dysfunction and serum levels of NSE and S100$\beta$ in elderly patients undergoing surgery. Eur Rev Med Pharmacol Sci. 2024; 28(1):278-87.
[19] Laishram K, Borgohain B, Laishram A, Khonglah TG, Ruram AA, Debbarma S. Serum IL-6 as a Surrogate Biomarker of Post-operative Complications in Invasive Orthopaedic Surgeries: A Prospective Observational Study. Indian J Orthop. 2024; 58(8):1153-8.
[20] Lv XC, Lin Y, Wu QS, Wang L, Hou YT, Dong Y, et al. Plasma interleukin-6 is a potential predictive biomarker for postoperative delirium among acute type a aortic dissection patients treated with open surgical repair. J Cardiothorac Surg. 2021; 16(1):146.
[21] Safavynia SA, Goldstein PA. The Role of Neuroinflammation in Postoperative Cognitive Dysfunction: Moving From Hypothesis to Treatment. Front Psychiatry. 2019; 9:752.
[22] Theodoridou A, Gika H, Diza E, Garyfallos A, Settas L. In vivo study of pro-inflammatory cytokine changes in serum and synovial fluid during treatment with celecoxib and etoricoxib and correlation with VAS pain change and synovial membrane penetration index in patients with inflammatory arthritis. Mediterr J Rheumatol. 2017; 28(1):33-40.
[23] Shieh JM, Tsai YJ, Ma MC, Chen CL, Wu WB. The cyclooxygenase-2 upregulation mediates production of PGE2 autacoid to positively regulate interleukin-6 secretion in chronic rhinosinusitis with nasal polyps and polyp-derived fibroblasts. Sci Rep. 2024; 14(1):7559.
[24] Zhang S, Tao XJ, Ding S, Feng XW, Wu FQ, Wu Y. Associations between postoperative cognitive dysfunction, serum interleukin-6 and postoperative delirium among patients after coronary artery bypass grafting: a mediation analysis. Nurs Crit Care. 2024; 29(6):1245-52.
[25] Li YC, Xi CH, An YF, Dong WH, Zhou M. Perioperative inflammatory response and protein S-100$\beta$ concentrations - relationship with post-operative cognitive dysfunction in elderly patients. Acta Anaesthesiol Scand. 2012; 56(5):595-600.
[26] Huang X, Li L, Feng Q. Correlation Analysis of Inflammatory Markers CRP and IL-6 and Postoperative Delirium (POD) in Elderly Patients: A Meta-Analysis of Observational Studies. J Environ Public Health. 2022; 2022:1136386.
[27] Song Y, Luo Y, Zhang F, Ma Y, Lou J, Li H, et al. Systemic immune-inflammation index predicts postoperative delirium in elderly patients after surgery: a retrospective cohort study. BMC Geriatr. 2022; 22(1):730.
[28] Tan XX, Qiu LL, Sun J. Research Progress on the Role of Inflammatory Mechanisms in the Development of Postoperative Cognitive Dysfunction. Biomed Res Int. 2021; 2021:3883204.
[29] Xue YH, Peng YS, Ting HF, Peijer Hsieh J, Huang YK, Wang YH, et al. Etoricoxib and Diclofenac Might Reduce the Risk of Dementia in Patients with Osteoarthritis: A Nation-Wide, Population-Based Retrospective Cohort Study. Dement Geriatr Cogn Disord. 2018; 45(5-6):262-71.
[30] Mohan P, Sharma AK, Sinha S, Sabarad R. An experimental study of rosuvastatin's analgesic effect and its interaction with etoricoxib, tramadol, amlodipine, and amitriptytline in albino mice. Med J Armed Forces India. 2022; 78 Suppl 1:S61-8.
[31] Singh MK, Kumar S, Dixit P, Singh V, Verma S, Singh GP. The effect of celecoxib on early postoperative cognitive dysfunction in elderly patients of fracture neck of femur: a prospective randomised double-blind study. Anaesth Pain Intensive Care. 2021; 25(3):287-94.
[32] Khaled M, Sabac D, Fuda M, Koubaesh C, Gallab J, Qu M, et al. Postoperative pain and neurocognitive outcomes after noncardiac surgery: a systematic review and dose–response meta-analysis. Br J Anaesth. 2025; 134(1):89-101.
[33] Du Y, Cao J, Gao C, He K, Wang S. Influence of intraoperative pain management on postoperative delirium in elderly patients: A prospective single-center randomized controlled trial. Pain Ther. 2025; 14(1):387-400.
[34] La Rosa GR, Consoli M, Abiad RS, Toscano A, Pedullà E. Comparing pre-and postoperative etoricoxib administration versus only postoperative on third molar extraction sequelae and oral health quality of life: a prospective quasi-experimental study. Clin Oral Investig. 2024; 28(4):218.
[35] Lierz P, Losch H, Felleiter P. Evaluation of a single preoperative dose of etoricoxib for postoperative pain relief in therapeutic knee arthroscopy: a randomized trial. Acta Orthop. 2012; 83(6):642-7.
[36] Srivastava S, Gupta D, Naz A, Rizvi MM, Singh PK. Effects of preoperative single dose Etoricoxib on postoperative pain and sleep after lumbar diskectomy: prospective randomized double blind controlled study. Middle East J Anaesthesiol. 2012; 21(5):725-30.
[37] Shi H, Du X, Wu F, Hu Y, Xv Z, Mi W. Dexmedetomidine improves early postoperative neurocognitive disorder in elderly male patients undergoing thoracoscopic lobectomy. Exp Ther Med. 2020; 20(4):3868-77.
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How to Cite
1.
Hasyim A, Gaus S, Wirawan N, Salahuddin A, Takdir Musba A, Adil A. Preoperative Treatment with Dexamethasone and Etoricoxib: A Comparison of Effects on Serum Interleukin-6 (IL-6) Levels and Postoperative Delirium (POD) in Geriatric Patients with General Anesthesia. Arch Anesth & Crit Care. 2026;.
