Comparison of Systemic Inflammatory Markers in Total Knee Arthroplasty Under Spinal vs General Anesthesia: A Retrospective Study

Comparison of Systemic Inflammatory Markers in Total Knee Arthroplasty Under Spinal vs General Anesthesia: A Retrospective Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Comparison of Systemic Inflammatory Markers in Total Knee Arthroplasty Under Spinal vs General Anesthesia: A Retrospective Study Ali Genç, Mehtap Gürler Balta, Vildan Kölükçü, Ahmet Tuğrul Şahin, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6810865/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 22 Oct, 2025 Read the published version in BMC Anesthesiology → Version 1 posted 6 You are reading this latest preprint version Abstract Purpose In total knee arthroplasty (TKA), both surgical trauma and the type of anesthesia administered can significantly affect systemic inflammation, which may influence postoperative recovery. This retrospective study aimed to compare perioperative changes in blood-derived systemic inflammatory markers—specifically the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI)—in patients undergoing TKA under general versus spinal anesthesia. Methods This retrospective analysis included 849 patients who underwent elective primary TKA between January 2020 and April 2025. Inclusion criteria were age 18–75 years and ASA physical status I–II. Patients with BMI ≥ 40 kg/m², ASA ≥ III, major comorbidities, active infection, revision surgery, or incomplete lab data were excluded. Patients were categorized into spinal anesthesia (Group S) and general anesthesia (Group G) groups. Pre- and postoperative hemograms were used to calculate SII and SIRI values; ΔSII and ΔSIRI were defined as absolute differences. Groups were compared in terms of inflammatory markers, total opioid requirement, postoperative complications, and hospital stay. Group comparability regarding age, ASA, and comorbidities was assessed, but no multivariate adjustment was performed due to the observational design. Results A total of 849 patients were included in the study. The median ΔSII value was significantly higher in the general anesthesia group [Group G: 1448.47 (IQR: 677.78–2670.86)] compared to the spinal anesthesia group [Group S: 1060.75 (IQR: 463.69–2093.28); p < 0.001]. Similarly, the ΔSIRI value was higher in Group G [4.56 (IQR: 2.31–9.23)] than in Group S [3.69 (IQR: 1.70–7.05); p = 0.002]. The total opioid requirement within the first 24 postoperative hours was also significantly greater in Group G (p < 0.001). No statistically significant differences were found between the groups in terms of postoperative complication rates (p = 0.48) or length of hospital stay (p = 0.18). Conclusion Compared to general anesthesia, spinal anesthesia was associated with a lower perioperative increase in systemic inflammatory blood markers in patients undergoing TKA. While no difference was observed in short-term clinical outcomes, these findings suggest that spinal anesthesia may offer an immunological advantage. Given the retrospective nature of the study, prospective research is warranted to determine whether these biomarker differences have meaningful clinical implications. Inflammation general anesthesia spinal anesthesia neutrophils total knee arthroplasty white blood cells Figures Figure 1 Figure 2 Introduction Systemic inflammation plays a critical role in postoperative recovery, influencing wound healing, pain, and the risk of complications. In the context of total knee arthroplasty (TKA), which is among the most commonly performed orthopedic surgeries for severe degenerative joint disease, both surgical trauma and the anesthetic technique may provoke varying degrees of systemic inflammatory response. This inflammatory activity may, in turn, influence short-term recovery, opioid requirements, and overall patient outcomes. Among the tools used to assess inflammation, hematological indices such as the systemic immune-inflammation index (SII = neutrophil × platelet / lymphocyte count) and systemic inflammation response index (SIRI = neutrophil × monocyte / lymphocyte count) have gained attention [ 1 ]. These indices provide accessible, cost-effective insights into the balance between immune activation and regulation [ 2 ]. Compared to conventional markers like C-reactive protein (CRP), interleukin-6 (IL-6), or tumor necrosis factor-alpha (TNF-α), SII and SIRI can be easily calculated from routine hemograms and do not require specialized assays. Prior studies have shown the predictive utility of these indices in various surgical and medical contexts, including gastrointestinal surgery, cardiac procedures, and oncologic outcomes [ 3 – 7 ]. For instance, elevated preoperative SII has been associated with sepsis following intestinal obstruction [ 3 ], while SIRI has predicted postoperative delirium in cardiac surgery patients [ 6 ]. However, their specific application in orthopedic procedures, particularly TKA, remains underexplored. The relationship between anesthesia type and systemic inflammation is another area of ongoing investigation. While some studies have found no significant difference in inflammatory marker levels between spinal and general anesthesia [ 8 , 9 ], others suggest that regional techniques may mitigate inflammatory responses more effectively [ 10 – 12 ]. These conflicting findings highlight the need for further studies using novel, sensitive inflammatory markers such as SII and SIRI. Reducing perioperative inflammation in TKA is clinically important because excessive systemic inflammatory responses may delay wound healing, increase postoperative pain and opioid consumption, and contribute to complications such as infection or thromboembolic events. Understanding how anesthesia choice may influence these inflammatory changes could help guide perioperative management strategies. This study aimed to retrospectively compare perioperative changes in SII and SIRI in patients undergoing TKA under spinal versus general anesthesia, and to assess their association with opioid use, complications, and hospital stay. Material and Method Following ethical approval from the Clinical Research Ethics Committee of Tokat Gaziosmanpasa University (Approval No: 25-MOBAEK-160), this retrospective observational cohort study was conducted to evaluate patients who underwent total knee arthroplasty (TKA) between January 2020 and April 2025. The study was registered on ClinicalTrials.gov (Identifier: NCT06984315) on May 21, 2025, after data collection had been completed. Registration was performed retrospectively because the study, by design, was non-interventional and observational, and was initially considered exempt from prospective registration. The decision to register post hoc was made to enhance transparency and align with best practices in research reporting. All patient data were anonymized before analysis. Medical records were reviewed by two authors with access to the hospital’s electronic database. Although the reviewers were not blinded to group assignment, they adhered to predefined data abstraction criteria. Eligibility Criteria A total of 1,292 patients were screened using consecutive sampling. Of these, 443 were excluded for the following reasons: 74 underwent revision total knee arthroplasty (TKA), 83 had ASA physical status scores of III or higher, 233 lacked laboratory data, 18 had missing or incomplete clinical documentation, and 35 underwent conversion from spinal to general anesthesia due to failed neuraxial block. After applying these exclusion criteria, 849 patients met the eligibility requirements and were included in the final analysis. After applying all eligibility criteria, 849 patients were included in the final analysis. Inclusion criteria were age 18–75 years and American Society of Anesthesiologists (ASA) physical status I–II. Patients were excluded for any of the following: BMI ≥ 40 kg/m², ASA ≥ III, significant cardiopulmonary or endocrine disease, chronic corticosteroid use, active infection, history of malignancy, intraoperative conversion of anesthesia type, emergency surgery, revision TKA, or incomplete laboratory or clinical records. Given the broad age range, baseline balance in age and other demographic variables was assessed statistically to ensure group comparability. Anesthesia type was not randomized; it was determined based on a combination of the patient’s clinical status and their individual preference, in consultation with the attending anesthesiologist. Data Collection Demographic characteristics, clinical data, and laboratory values were extracted from patient records. Preoperative hemograms were obtained 1 day before surgery. Postoperative blood samples were included only if collected within the predefined 4–12 hour postoperative window; patients lacking laboratory data within this interval were excluded. Inflammatory indices were calculated as: SII = (neutrophils × platelets) / lymphocytes, SIRI = (neutrophils × monocytes) / lymphocytes. Absolute changes (ΔSII, ΔSIRI) were defined as the absolute difference between postoperative and preoperative values. Total opioid consumption was recorded in morphine milligram equivalents (MME) within the first 24 hours postoperatively. Postoperative complications and hospital length of stay were also recorded.The primary outcomes of the study were absolute ΔSII and ΔSIRI. Secondary outcomes included total opioid consumption, length of hospital stay, and postoperative complications such as nausea, vomiting, and wound site infection. Patients were excluded if they had missing laboratory results, incomplete clinical documentation, or insufficient postoperative follow-up data. Anesthesia Protocols Patients received either spinal anesthesia (Group S) or general anesthesia (Group G). In Group S, 3 mL of 0.5% hyperbaric bupivacaine was administered intrathecally at L3–L4 or L4–L5 with a 25G Quincke spinal needle. In Group G, induction included propofol (2 mg/kg), fentanyl (2 mcg/kg), and rocuronium (0.6 mg/kg), followed by endotracheal intubation and maintenance with sevoflurane (age-adjusted MAC of 1.0). Surgical Technique All surgeries were performed by one of three experienced orthopedic surgeons (coded as A, B, and E for anonymization), each with more than 10 years of clinical experience. The same standardized medial parapatellar approach was used across all procedures. Postoperative Analgesia A standardized analgesic regimen was used across all patients. Scheduled intravenous paracetamol (1 g every 6 hours) and intramuscular diclofenac sodium (75 mg twice daily) were administered. Patients reporting a numeric rating scale (NRS) score ≥ 4 received intravenous tramadol as first-line rescue analgesia. If pain persisted, intravenous morphine (3 mg) was administered. Analgesia was administered by ward staff involved in postoperative care, who were aware of the anesthesia type. Due to the retrospective design and the routine clinical workflow, blinding was not applicable. A post-hoc power analysis was conducted for the primary outcome variable (ΔSII), based on the observed Z value from the Mann-Whitney U test (Z = − 3.552) and total sample size (N = 849). The corresponding effect size, calculated as the rank-biserial correlation coefficient, was r = 0.122, indicating a small effect. Despite this, the analysis yielded a statistical power of approximately 82% (1 − β = 0.82) at an alpha level of 0.05, confirming that the sample size was sufficient to detect a significant difference in ΔSII between anesthesia groups. Statistical Analysis The normality of continuous variables was assessed using the one-sample Kolmogorov-Smirnov test. Categorical variables were expressed as frequencies and percentages, while non-normally distributed continuous variables were presented as medians with interquartile ranges [median (IQR)]. Group comparisons for categorical variables were performed using the chi-square test. The Mann-Whitney U test was applied to compare preoperative and postoperative SII and SIRI values, ΔSII, ΔSIRI, and total opioid consumption between groups. Within-group comparisons of NLR, PLR, SII, and SIRI (pre- vs. postoperative) were conducted using the Wilcoxon signed-rank test for both the spinal (Group S) and general anesthesia (Group G) cohorts. In addition, multiple linear regression models were constructed to assess the association between anesthesia type and ΔSII/ΔSIRI, considering potential confounders such as age, sex, BMI, ASA class, comorbidities, surgical duration, and other relevant clinical or procedural factors. All analyses were performed using SPSS software (Version 20.0, SPSS Inc., Chicago, IL, USA), and a p-value < 0.05 was considered statistically significant. Results Of the 1,292 patients initially screened for eligibility, 443 were excluded from the final analysis due to the following reasons: 74 underwent revision total knee arthroplasty, 83 had an ASA physical status classification of III or higher, 233 lacked perioperative laboratory data, 18 had missing or incomplete clinical documentation, and 35 experienced failed spinal anesthesia that required conversion to general anesthesia. As a result, 849 patients met all inclusion criteria and were included in the final analysis. The study's flow chart is in Fig. 1 . The median [interquartile range (IQR)] age of the patient population was 67 (61–71) years and 83% were women. Table 1 demonstrates demographic data and descriptive characteristics of the patients in detail. No statistically significant differences were observed between the groups in terms of demographic variables and calculated preoperative inflammation indices (Table 1 ). Table 1 Baseline Characteristics and Clinical Outcomes of the Study Population Group S Group G p Age (years) 67 (61 – 72) 66 (61–71) 0.31 a Sex (Female / Male): n (%) 537 / 107 (83.4 / 16.6) 167 / 38 (81.5 / 18.5) 0.52 b BMI (kg/m 2 ) 28.93 (24.16–30.11) 28.65 (24.09–30.11) 0.8 a ASA Score: (I/II): n (%) 116 / 528 (18 / 82) 45 / 160 (22 / 78) 0.21 b Duration of surgery (min) 120 (90 – 120) 120 (90 – 120) 0.19 a Hypertension: n (%) 137 (21.3) 41 (20) 0.7 b Diabetes: n (%) 80 (12.4) 21 (10.2) 0.4 b Ischemic heart disease: n (%) 57 (8.9) 19 (9.3) 0.9 b Chronic lung Disease: n (%) 79 (12.3) 24 (11.7) 0.83 b Thyroid disease: n (%) 39 (6.1) 17 (8.3) 0.34 b Cerebral vascular disease: n (%) 41 (6.4) 12 (5.9) 0.79 b Neoplasm: n (%) 12 (1.9) 3 (1.5) 0.71 b Rheumatic disease: n (%) 46 (7.1) 9 (4.4) 0.21 b Smoking: n (%) 60 (9.3) 18 (8.8) 0.93 b INR (preoperative) 1.05 (0.98–1.14) 1.05 (0.97–1.12) 0.3 a NLR (preoperative) 2.33 (1.64–3.77) 2.22 (1.59–3.44) 0.35 a PLR (preoperative) 127.75 (99.64–170.85) 128.33 (95.69–172.76) 0.9 a SII (preoperatif) 606.24 (419.72–968.71) 555.7 (407.29–1000.83) 0.84 a SIRI (preoperatif) 1.28 (0.86–2.33) 1.32 (0.78–2.02) 0.22 a a Mann-Whitney U test; b Pearson Chi-Square test; Quantitative data are given as median [interquartile range (IQR)] (BMI: Body Mass İndex; ASA: American Society of Anesthesiologists; NLR: neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; SII: systemic immune inflammation index; SIRI: systemic inflammation response index) The median (IQR) ΔSII and ΔSIRI values for all patients were 1147.17 (517.69–2261.74) and 3.96 (1.85–7.28), respectively. Group G showed significantly higher ΔSII [1448.47 (677.78–2670.86)] and ΔSIRI [4.56 (2.31–9.23)] values compared to Group S [ΔSII: 1060.75 (463.69–2093.28); ΔSIRI: 3.69 (1.70–7.05)] (p < 0.001, p = 0.002, respectively), (Table 2 ). Preoperative SII and SIRI values were similar between groups (p = 0.84, p = 0.22 respectively), as were preoperative NLR and PLR (p = 0.35, p = 0.9, respectively), (Table 1 ). In contrast, postoperative values of SII, SIRI, NLR, and PLR were significantly higher in Group G compared to Group S (p = 0.001, p = 0.002, p = 0.001, p = 0.01, respectively), (Table 2 ). Corresponding median (IQR) values for postoperative SII were 2011.46 (1287.67–3130.72) in Group G and 1649.36 (1041.93–2801.83) in Group S; for SIRI: 4.56 (2.31–9.23) and 3.69 (1.70–7.05). Table 2 Comparison of some patients' outcomes in general and spinal anesthesia Group S Group G p r NLR (postoperative) 7.25 (4.65–10.97) 8.19 (5.57–12.57) 0.001 a * 0.11 PLR (postoperative) 187.69 (127.16–271.87) 211.52 (143.23–281.25) 0.01 a * 0.088 SII (postoperative) 1649.36 (1041.93–2801.83) 2011.46 (1287.67–3130.72) 0.001 a * 0.113 SIRI(postoperative) 4.94 (2.76–8.25) 5.67 (3.68–10.46) 0.002 a * 0.108 ΔSII 1060.75 (463.69–2093.28) 1448.47 (677.78–2670.86) < 0.001 a * 0.122 ΔSIRI 3.69 (1.7–7.05) 4.56 (2.31–9.23) 0.002 a * 0.122 Surgeon (A / B / E): n (%) 241 / 215 / 188 (37.4 /33.4 / 29.2) 74 / 66 / 65 (36.1 / 32.2 / 31.7) 0.79 b Surgical duration (minute) 120 (90 – 120) 120 (96–120) 0.19 a Postoperative total opioid consumed (morphine milligram equivalents) 5 (5–10) 10 (5–15) < 0.001* 0.134 Nausea: n (%) 28 (4.3) 12 (5.9) 0.35 b Vomiting: n (%) 21 (3.3) 9 (4.4) 0.51 b Surgical site infection: n (%) 5 (0.8) 2 (1) 0.68 b Total length of hospital stay (day) 3 (3–4) 3 (3–4) 0.18 a a Mann-Whitney U test; b Chi-Square tes*; statistically significant; Quantitative data are given as median [interquartile range (IQR)]; r: Rank-biserial correlation coefficient. Calculated using the formula r = Z / √N, where Z is the test statistic from the Mann-Whitney U test and N is the total sample size. (NLR: neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; SII: systemic immune inflammation index; SIRI: systemic inflammation response index; ΔSII = |SII (postoperatif) -SII (preoperatif)|; ΔSIRI = |SIRI (postoperatif) - SIRI (preoperatif)|; Surgeon A, B, and E refer to the anonymized identifiers of the three orthopedic surgeons who performed the procedures) In both groups, postoperative values of all inflammatory markers (SII, SIRI, NLR, and PLR) showed a significant increase compared to preoperative values (p < 0.001 for all), (Fig. 2 ). These within-group elevations were observed consistently, regardless of anesthesia type. Figure 2 presents boxplots depicting these changes over time, enabling visual comparison of inflammatory marker dynamics between the spinal and general anesthesia groups. Wilcoxon signed-ranks test; : statistically significant different from preoperative Group S; : statistically significant different from postoperative Group S; : statistically significant different from preoperative Group G; : statistically significant different from preoperative Group G. (NLR: neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; SII: systemic immune inflammation index; SIRI: systemic inflammation response index) In the multivariate linear regression analysis evaluating predictors of the absolute ΔSII, anesthesia type and ischemic heart disease emerged as statistically significant independent predictors. Patients who received general anesthesia exhibited a significantly greater increase in ΔSII compared to those who underwent spinal anesthesia (B = 407.72, 95% CI: 151.60 to 663.84, p = 0.002). In contrast, the presence of ischemic heart disease was associated with a significantly lower ΔSII (B = -716.06, 95% CI: -1189.44 to -242.69, p = 0.003). Other demographic and clinical variables were not significantly associated with absolute ΔSII. Complete results of the regression model are presented in Table 3 . Table 3 Multivariate Linear Regression Analysis for Predictors of the Absolute Change in Perioperative SII (ΔSII) Independent Variables Unstandardized Coefficients Standardized Coefficients Sig. ( p ) 95% Confidence Interval for B B Std. Error Beta Lower Bound Upper Bound Anesthesia Type (Spinal / General) 407.720 130.487 0.111 0.002* 151.597 663.842 Sex (Female / Male) -68.299 148.262 -0.016 0.645 -359.312 222.714 BMI (kg/m2) -6.387 16.271 -0.014 0.695 -38.323 25.549 Age (years) -21.053 8.879 -0.089 0.078 -38.482 -3.624 ASA Score: (I / II) 235.727 152.136 0.059 0.122 -62.889 534.343 Hypertension 42.324 146.951 0.011 0.773 -246.116 330.764 Diabetes 46.334 175.423 0.010 0.792 -297.992 390.659 Ischemic heart disease -716.063 241.170 -0.130 0.003* -1189.437 -242.688 Chronic lung Disease 178.032 210.052 0.037 0.397 -234.264 590.329 Thyroid disease -291.383 224.443 -0.046 0.195 -731.926 149.159 Cerebral vascular disease 174.163 250.249 0.027 0.487 -317.033 665.358 Neoplasm -201.383 408.490 -0.017 0.622 -1003.178 600.413 Rheumatic disease 72.013 218.485 0.011 0.742 -356.835 500.861 Smoking 84.665 193.950 0.016 0.663 -296.024 465.355 Surgical duration (min) 3.695 2.467 0.051 0.135 -1.147 8.537 Total opioid consumed (MME) 1.237 1.130 0.039 0.274 -0.981 3.454 SII (preoperatif) 0.101 0.065 0.054 0.119 -0.026 0.228 Surgeon (B / E / Z) -85.366 65.923 -0.044 0.196 -214.762 44.029 Multiple Logistic Regression Analysis; Statistically significant results (p < 0.05) are indicated with an asterisk (*) (BMI = body mass index; MME = morphine milligram equivalent; SII = systemic immune inflammation index) In the multivariate linear regression analysis evaluating the predictors of the absolute ΔSIRI, anesthesia type and ischemic heart disease were found to be statistically significant independent predictors. Receiving general anesthesia was associated with a significantly higher increase in ΔSIRI compared to spinal anesthesia (B = 1.150, 95% CI: 0.262 to 2.037, p = 0.011). Conversely, the presence of ischemic heart disease was associated with a significantly lower ΔSIRI (B = -2.467, 95% CI: -4.121 to -0.813, p = 0.004). Other variables did not show statistically significant associations with ΔSIRI. The full results of the regression analysis are presented in Table 4 . Table 4 Multivariate Linear Regression Analysis for Predictors of the Absolute Change in Perioperative SIRI (ΔSIRI) Independent Variables Unstandardized Coefficients Standardized Coefficients Sig.( p ) 95% Confidence Interval for B B Std. Error Beta Lower Bound Upper Bound Anesthesia Type (Spinal / General) 1.150 0.452 0.091 0.011* 0.262 2.037 Sex (Female / Male) -0.126 0.515 -0.009 0.807 -1.137 0.886 BMI (kg/m2) 0.086 0.056 0.053 0.127 -0.024 0.196 Age (years) -0.054 0.031 -0.066 0.081 -0.114 0.007 ASA Score: (I / II) 0.456 0.525 0.033 0.385 -0.574 1.486 Hypertension 0.534 0.510 0.040 0.295 -0.467 1.534 Diabetes -0.229 0.606 -0.014 0.705 -1.418 0.960 Ischemic heart disease -2.467 0.843 -0.130 0.004* -4.121 -0.813 Chronic lung Disease 1.321 0.727 0.080 0.070 -0.106 20.747 Thyroid disease -0.924 0.775 -0.042 0.234 -2.446 0.598 Cerebral vascular disease -0.059 0.865 -0.003 0.946 -1.756 1.639 Neoplasm -1.179 1.411 -0.029 0.403 -3.948 1.590 Rheumatic disease 0.730 0.754 0.033 0.334 -0.751 2.210 Smoking -0.382 0.670 -0.020 0.569 -1.697 0.934 Surgical duration (min) 0.004 0.009 0.017 0.610 -0.012 0.021 Total opioid consumed (MME) 0.005 0.004 0.049 0.171 -0.002 .0013 SIRI (preoperatif) 0.159 0.070 0.078 0.093 0.022 0.297 Surgeon (B / E / Z) -0.200 0.228 -0.030 0.381 -0.648 0.248 Multiple Logistic Regression Analysis; Statistically significant results (p < 0.05) are indicated with an asterisk (*) (BMI = body mass index; MME = morphine milligram equivalent; SIRI = systemic inflammation response index) There were no statistically significant differences between the groups in terms of the operating surgeon distribution or the duration of surgery (p = 0.79 and p = 0.19, respectively), indicating that intraoperative conditions were comparable across anesthesia types (Table 2 ). There were no statistically significant differences between groups regarding the distribution of operating surgeons or surgical duration (p = 0.79 and p = 0.90, respectively), (Table 2 ), supporting the procedural consistency between groups. The median (IQR) postoperative total opioid consumed (MME) dose was 5 (5–10) in Group S and 10 (5–15) in Group G (Table 2 ). The total amount of opioids consumed postoperatively was significantly greater in Group G than in Group S (p < 0.001), (Table 2 ). To assess the clinical relevance of statistically significant differences, rank-biserial correlation coefficients (r) were calculated. Effect sizes were small across all comparisons: NLR (r = 0.110), PLR (r = 0.088), postoperative SII (r = 0.113), postoperative SIRI (r = 0.108), ΔSII (r = 0.122), ΔSIRI (r = 0.122), and total opioid consumption (r = 0.134). Postoperative complications were infrequent and comparable between groups. The most common adverse event was nausea, reported in 4.3% of patients in Group S and 5.9% in Group G (p = 0.35). Vomiting occurred in 3.3% and 4.4% of patients, respectively (p = 0.51). Surgical site infections were rare, observed in 0.8% of patients in Group S and 1.0% in Group G (p = 0.68). All infections were classified as superficial and managed conservatively with antibiotics, without the need for surgical intervention. Among patients who developed infection, the median (IQR) length of hospital stay was 4 (3–5) days, compared to 3 (3–4) days in those without infection; however, this difference was not statistically significant (p = 0.20), possibly due to the small number of cases and the mild nature of the infections. These events were transient and did not result in reoperation or substantial prolongation of hospitalization. An exploratory Spearman correlation analysis was performed to evaluate the relationship between inflammatory response and postoperative opioid consumption. The results demonstrated no statistically significant correlation between ΔSII and MME (r = 0.058, p = 0.09), or between ΔSIRI and MME (r = 0.052, p = 0.13). These findings suggest that the magnitude of the inflammatory response may not be directly associated with the amount of opioid required in the early postoperative period. Discussion Our findings suggest that spinal anesthesia may attenuate the systemic inflammatory response following TKA, as evidenced by significantly lower postoperative SII and SIRI values compared to general anesthesia.. Although the differences in ΔSII and ΔSIRI were statistically significant, further studies are needed to determine whether these changes translate into meaningful clinical outcomes. Previous studies have yielded conflicting results regarding the effect of anesthetic technique on systemic inflammatory response. Eroğlu et al. reported no significant differences in IL-6, IL-8, TNF-α, and CRP levels between spinal and general anesthesia in TKA patients [ 9 ]. Similarly, Büyükocak et al. found comparable levels of IL-6, TNF-α, CRP, cortisol, and leptin in patients undergoing hemorrhoidectomy under either technique [ 13 ]. On the other hand, other studies have demonstrated that regional techniques may mitigate inflammatory response. For instance, Gültekin et al. showed that epidural analgesia reduced perioperative SII increases in radical prostatectomy compared to general anesthesia alone [ 10 ]. Symeonidis et al. reported that spinal anesthesia led to a lower postoperative CRP rise than general anesthesia in open hernia repair [ 11 ], and Žura et al. demonstrated that general anesthesia caused a greater increase in IL-2 levels compared to spinal anesthesia in transurethral prostate resection procedures [ 12 ]. SII and SIRI are novel hematological markers derived from routine complete blood counts, reflecting the interplay between innate immunity and systemic inflammation [ 1 , 2 ]. Due to their accessibility and cost-effectiveness, they have gained attention as practical alternatives to conventional biomarkers such as CRP, IL-6, IL-8, and TNF-α, which are more expensive and less feasible for routine use [ 14 , 15 ]. Several studies have demonstrated the prognostic utility of SII and SIRI across a range of clinical settings, including gastrointestinal and cardiovascular surgeries [ 3 – 9 ]. While these findings support their broader clinical relevance, caution is warranted when extrapolating results to orthopedic procedures like TKA, given the differences in surgical stress and patient characteristics. Compared to other hematologic indices like NLR and PLR, SII and SIRI have shown superior prognostic performance in various malignancies and systemic diseases [ 16 – 20 ]. Their reproducibility, low cost, and strong correlation with clinical outcomes make them promising tools for perioperative inflammatory monitoring, especially in large-scale or resource-limited settings. Recent orthopedic studies have also explored clinical outcomes between spinal and general anesthesia in TKA. While some reported lower complication and readmission rates with spinal anesthesia [ 21 , 22 ], others, such as Stambough et al., emphasized that optimized general anesthesia protocols could yield comparable outcomes [ 23 ]. Our findings support the view that anesthetic technique may influence physiological parameters without necessarily affecting short-term clinical endpoints in lower-risk TKA patients. The lack of difference in complication rates and hospital stay may reflect the relatively low-risk profile of the study population (ASA I–II), and the effectiveness of standardized perioperative care protocols. Multiple logistic regression analysis revealed that general anesthesia was significantly associated with higher odds of increased perioperative SII and SIRI levels compared to spinal anesthesia, indicating a stronger systemic inflammatory response. Additionally, ischemic heart disease was independently associated with lower odds of elevated inflammatory indices. This inverse association aligns with findings from Ma and Li, who reported that higher SII levels were linked to a reduced prevalence of coronary artery disease in a large NHANES-based population [ 24 ]. These results may reflect immune adaptation or anti-inflammatory regulation in patients with chronic cardiovascular disease. One of the main limitations of this study is its retrospective design. Additionally, the study was conducted in a single center and included only patients with ASA physical status scores of I or II undergoing primary TKA. In higher-risk populations—such as those with ASA III or greater and significant functional impairment—perioperative systemic inflammatory responses may be more pronounced and clinically relevant. Another ilimitation is the lack of precise standardization in the timing of postoperative blood sampling. Although all samples were obtained within a consistent 4–12-hour window, this variability may still have introduced minor fluctuations in inflammatory marker measurements. Future studies could benefit from fixed sampling intervals or time-adjusted analyses to address this issue. Finally, potential selection bias should be acknowledged. Anesthesia type was not randomized and may have been influenced by patient characteristics or clinician preference. Although key baseline variables such as ASA and BMI were statistically comparable between groups, residual confounding from unmeasured factors—such as frailty, undiagnosed comorbidities, or provider discretion—cannot be excluded. These limitations are inherent to the retrospective design and the lack of detailed covariate data. Prospective randomized controlled, multicenter studies involving more heterogeneous populations (including patients with ASA scores ≥ III) are needed to evaluate the generalizability of these findings. In addition, studies that incorporate serial inflammatory marker measurements at standardized perioperative time points may offer deeper insights into the dynamics of systemic inflammation and its clinical implications. In conclusion, spinal anesthesia was associated with a milder systemic inflammatory response compared to general anesthesia in patients undergoing TKA. These findings support the hypothesis that spinal anesthesia may offer immunological advantages in TKA, particularly in patients where minimizing systemic inflammation is clinically desirable. However, due to the retrospective and observational nature of this study and the absence of differences in major clinical outcomes such as complication rates and hospital stay, spinal anesthesia cannot yet be definitively recommended as superior. Further prospective, randomized studies are necessary to validate these findings and better define the clinical implications of anesthesia choice in TKA. Declarations Funding: The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests: The authors have no relevant financial or non-financial interests to disclose. Author contributions: All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Ali Genc], [Sezer Astan], [Mehtap Gürler Balta], [Vildan Kölükçü], [Ahmet Tuğrul Şahin], [Hakan Tapar] and [Tugba Karaman], [Serkan Karaman]. The first draft of the manuscript was written by [Ali Genc] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript. Ethics approval: This retrospective study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Approval was granted by the Ethics Committee of Tokat Gaziosmanpaşa University (2025 / 25-MOBAEK-160). Clinical Trial Registration: The study was retrospectively registered on ClinicalTrials.gov with the registration number NCT06984315. At the time of study initiation, prospective registration was not deemed necessary due to its retrospective and non-interventional nature. The study was registered post hoc in the interest of transparency. Consent to participate : Waived, as the study involved anonymized retrospective data and individual patient consent was not required according to the guidelines of the Tokat Gaziosmanpasa University Clinical Research Ethics Committee. Consent for publication: Not applicable Data availability: The data supporting the findings of this study are available from the corresponding author upon reasonable request. Interested researchers may contact the corresponding author via email and provide a brief description of their intended use. References Balta S, Celik T, Mikhailidis DP, Ozturk C, Demirkol S, Aparci M, Iyisoy A. The relation between atherosclerosis and the neutrophil–lymphocyte ratio. Clin Appl Thromb Hemost. 2016;22(5):405–11. Beşir A, Tuğcugil E, Akdoğan A, Livaoğlu M. Neutrophil/lymphocyte ratio as a predictor of severe postoperative edema and ecchymosis in open rhinoplasty surgery. Cukurova Med J. 2022;47(4):1568–77. Yang J, Ran T, Lin X, Xu J, Zhou S, Chen C, Huang P. Association between preoperative systemic immune inflammation index and postoperative sepsis in patients with intestinal obstruction: A retrospective observational cohort study. Immun Inflamm Dis. 2024;12(2):e1187. Feng L, Xu R, Lin L, Liao X. Effect of the systemic immune-inflammation index on postoperative complications and the long-term prognosis of patients with colorectal cancer: a retrospective cohort study. J Gastrointest Oncol. 2022;13(5):2333–9. Schietroma M, Romano L, Schiavi D, Pessia B, Mattei A, Fiasca F, et al. Systemic inflammation response index (SIRI) as predictor of anastomotic leakage after total gastrectomy for gastric cancer. Surg Oncol. 2022;43:101791. Zhao B-s, Zhai W-q, Ren M, Zhang Z, Han J-g. Systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) as predictors of postoperative delirium in patients undergoing off-pump coronary artery bypass grafting (OPCABG) with cerebral infarction. BMC Surg. 2024;24(1):338. Xie L-f, Xie Q-g, Gao W-p, Wu Q-s, Lin X-f, Qiu Z-h. Chen L-w. The prognostic value of preoperative systemic inflammatory response index in predicting outcomes of acute type A aortic dissection patients underwent surgical treatment. Front Immunol. 2024;15:1388109. Wang Q, Lin F, Huang B, Pan LH. The effectiveness and safety of general and spinal anesthesia on systemic inflammatory response in patients with tumor-type total knee arthroplasty. Oncol Res Treat. 2020;43(9):428–34. Eroğlu M, Kokulu S, Koca HB, Demirboğan ME, Baki ED, Özcan Ö. The effects of general and spinal anesthesia on systemic inflammatory response in patients undergoing total knee arthroplasty. Jt Dis Relat Surg. 2016;27(3):153–9. Gultekin A, Sahin A, Akgul M, Yildirim I, Altinoz K, Baran O, Arar C. The Effect of Epidural Analgesia Added to General Anesthesia on Systemic Immune-Inflammation Index in Radical Prostatectomy Surgery: A Retrospective Study. Niger J Clin Pract. 2022;25(6):855–60. Symeonidis D, Diamantis A, Baloyiannis I, Tzovaras G, Tepetes K. Systemic immune response after open tension-free inguinal hernia repair under different anesthetic alternatives: a prospective comparative study. G Chir. 2020;41(1):103–9. Žura M, Kozmar A, Šakić K, Malenica B, Hrgovic Z. Effect of spinal and general anesthesia on serum concentration of pro-inflammatory and anti-inflammatory cytokines. Immunobiology. 2012;217(6):622–7. Buyukkocak U, Caglayan O, Daphan C, Aydinuraz K, Saygun O, Kaya T, Agalar F. Similar effects of general and spinal anaesthesia on perioperative stress response in patients undergoing haemorrhoidectomy. Mediators Inflamm. 2006;2006(1):097257. Bravo-Cuéllar A, Romero-Ramos JE, Hernández-Flores G, Romo-Pérez Fde J, Bravo-Cuéllar L, Lerma-Díaz JM. [Comparison of two types of anesthesia on plasma levels of inflammatory markers]. Cir Cir. 2007;75(2):99–105. Janet J, Derbal S, Durand Fontanier S, Bouvier S, Christou N, Fabre A, et al. C-reactive protein is a predictive factor for complications after incisional hernia repair using a biological mesh. Sci Rep. 2021;11(1):4379. Denegri A, Obeid S, Raeber L, Windecker S, Gencer B, Mach F, et al. Systemic immune-inflammation index predicts major adverse cardiovascular events in patients with ST-elevation myocardial infarction. Eur Heart J. 2021;42(Supplement1):ehab724. Chen JH, Zhai ET, Yuan YJ, Wu KM, Xu JB, Peng JJ, et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol. 2017;23(34):6261–72. Zhang Y, Xiao G, Wang R. Clinical significance of systemic immune-inflammation index (SII) and C-reactive protein-to-albumin ratio (CAR) in patients with esophageal cancer: a meta-analysis. Cancer Manag Res. 2019;11:4185–200. Agus HZ, Kahraman S, Arslan C, Yildirim C, Erturk M, Kalkan AK, Yildiz M. Systemic immune-inflammation index predicts mortality in infective endocarditis. J Saudi Heart Assoc. 2020;32(1):58–64. Liu Z, Ge H, Miao Z, Shao S, Shi H, Dong C. Dynamic Changes in the Systemic Inflammation Response Index Predict the Outcome of Resectable Gastric Cancer Patients. Front Oncol. 2021;11:577043. Heckmann ND, De A, Porter KR, Stambough JB. Spinal versus general anesthesia in total knee arthroplasty: are there differences in complication and readmission rates? J Arthroplasty. 2023;38(4):673–9. e1. Owen AR, Amundson AW, Larson DR, Duncan CM, Smith HM, Johnson RL, et al. Spinal versus general anaesthesia in contemporary primary total knee arthroplasties. Bone Joint J. 2022;104(11):1209–14. Stambough JB, Bloom GB, Edwards PK, Mehaffey GR, Barnes CL, Mears SC. Rapid recovery after total joint arthroplasty using general anesthesia. J Arthroplasty. 2019;34(9):1889–96. Ma J, Li K. Systemic immune-inflammation index is associated with coronary heart disease: a cross-sectional study of NHANES 2009–2018. Front Cardiovasc Med. 2023;10:1199433. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 22 Oct, 2025 Read the published version in BMC Anesthesiology → Version 1 posted Editorial decision: Revision requested 29 Aug, 2025 Reviews received at journal 17 Aug, 2025 Reviewers agreed at journal 17 Aug, 2025 Reviewers invited by journal 15 Aug, 2025 Submission checks completed at journal 08 Aug, 2025 First submitted to journal 03 Aug, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6810865","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":494851894,"identity":"ba117d1c-da19-46be-a74d-7d9640289e5f","order_by":0,"name":"Ali Genç","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA3ElEQVRIie3RMQrCMBSA4YRAXISsLai9QkrBpZdJF3uFDh0CQl2Urt29g7PwIC4F1w4O7eKs4OAkNrWubUbB/MMLgXwkEIRstl9sgmW3ss+WGBDSE1d+CR0l/cqPpoSticSP5OIF572qURJG0tvVg8QBLMmsvPqH6hpzVMaRpBM+fI0mbgZiWZVLB2fQkpGXeR15gQgKTV4GhLcE3yUIzrYtkQbEbwkgBX5R0ZgLFQcZXQ2TxWnTNM8UPJaDqm9pOM+JGiY6mOrpCIoEMvhJHX7qyY5Gh202m+0PewNhN0QnZuI6ygAAAABJRU5ErkJggg==","orcid":"","institution":"Tokat Gaziosmanpasa University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Ali","middleName":"","lastName":"Genç","suffix":""},{"id":494851895,"identity":"cceb46b7-783a-4768-b658-14e030f0aed4","order_by":1,"name":"Mehtap Gürler Balta","email":"","orcid":"","institution":"Tokat Gaziosmanpasa University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Mehtap","middleName":"Gürler","lastName":"Balta","suffix":""},{"id":494851896,"identity":"b689bc86-0171-4b9e-bd69-6fadc0f0ad72","order_by":2,"name":"Vildan Kölükçü","email":"","orcid":"","institution":"Tokat Gaziosmanpasa University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Vildan","middleName":"","lastName":"Kölükçü","suffix":""},{"id":494851897,"identity":"21d68373-8769-41ce-97c8-e0771d862143","order_by":3,"name":"Ahmet Tuğrul Şahin","email":"","orcid":"","institution":"Tokat Gaziosmanpasa University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ahmet","middleName":"Tuğrul","lastName":"Şahin","suffix":""},{"id":494851898,"identity":"9528054d-8b01-4288-adb6-a92c7a9809d7","order_by":4,"name":"Hakan Tapar","email":"","orcid":"","institution":"Tokat Gaziosmanpasa University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Hakan","middleName":"","lastName":"Tapar","suffix":""},{"id":494851899,"identity":"d47f102b-123b-45cf-a660-03e97d41f734","order_by":5,"name":"Tuğba Karaman","email":"","orcid":"","institution":"Tokat Gaziosmanpasa University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tuğba","middleName":"","lastName":"Karaman","suffix":""},{"id":494851900,"identity":"3c6e5928-dee6-495f-a26d-369f80c37919","order_by":6,"name":"Serkan Karaman","email":"","orcid":"","institution":"Tokat Gaziosmanpasa University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Serkan","middleName":"","lastName":"Karaman","suffix":""}],"badges":[],"createdAt":"2025-06-03 11:39:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6810865/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6810865/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12871-025-03399-y","type":"published","date":"2025-10-22T16:16:24+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":88421477,"identity":"00d0156c-9d44-443d-9c79-1a5a475e1a2a","added_by":"auto","created_at":"2025-08-06 09:29:53","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":247829,"visible":true,"origin":"","legend":"\u003cp\u003eFlow Diagram of the Study\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6810865/v1/303ecffa081b4261f24708d0.jpeg"},{"id":88419697,"identity":"73343773-ed88-482d-86f3-8afa4c51682c","added_by":"auto","created_at":"2025-08-06 09:21:53","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":288030,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of preoperative and postoperative inflammatory indices in general and spinal anesthesia\u003c/p\u003e\n\u003cp\u003eWilcoxon signed-ranks test; : statistically significant different from preoperative Group S; : statistically significant different from postoperative Group S; : statistically significant different from preoperative Group G; \u003csup\u003e\u0026nbsp;\u003c/sup\u003e: statistically significant different from preoperative Group G.\u003c/p\u003e\n\u003cp\u003e(NLR: neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; SII: systemic immune inflammation index; SIRI: systemic inflammation response index)\u003c/p\u003e","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-6810865/v1/5c04e1ce01c703cab0f20b69.jpeg"},{"id":94490274,"identity":"e94f6427-6180-477c-9bc4-17cad035cf2b","added_by":"auto","created_at":"2025-10-27 17:08:49","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1479245,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6810865/v1/48b1e090-b1d9-42d6-b08e-9c8433ddfaa1.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparison of Systemic Inflammatory Markers in Total Knee Arthroplasty Under Spinal vs General Anesthesia: A Retrospective Study","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSystemic inflammation plays a critical role in postoperative recovery, influencing wound healing, pain, and the risk of complications. In the context of total knee arthroplasty (TKA), which is among the most commonly performed orthopedic surgeries for severe degenerative joint disease, both surgical trauma and the anesthetic technique may provoke varying degrees of systemic inflammatory response. This inflammatory activity may, in turn, influence short-term recovery, opioid requirements, and overall patient outcomes.\u003c/p\u003e\u003cp\u003eAmong the tools used to assess inflammation, hematological indices such as the systemic immune-inflammation index (SII\u0026thinsp;=\u0026thinsp;neutrophil \u0026times; platelet / lymphocyte count) and systemic inflammation response index (SIRI\u0026thinsp;=\u0026thinsp;neutrophil \u0026times; monocyte / lymphocyte count) have gained attention [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. These indices provide accessible, cost-effective insights into the balance between immune activation and regulation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Compared to conventional markers like C-reactive protein (CRP), interleukin-6 (IL-6), or tumor necrosis factor-alpha (TNF-α), SII and SIRI can be easily calculated from routine hemograms and do not require specialized assays. Prior studies have shown the predictive utility of these indices in various surgical and medical contexts, including gastrointestinal surgery, cardiac procedures, and oncologic outcomes [\u003cspan additionalcitationids=\"CR4 CR5 CR6\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. For instance, elevated preoperative SII has been associated with sepsis following intestinal obstruction [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], while SIRI has predicted postoperative delirium in cardiac surgery patients [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. However, their specific application in orthopedic procedures, particularly TKA, remains underexplored.\u003c/p\u003e\u003cp\u003eThe relationship between anesthesia type and systemic inflammation is another area of ongoing investigation. While some studies have found no significant difference in inflammatory marker levels between spinal and general anesthesia [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], others suggest that regional techniques may mitigate inflammatory responses more effectively [\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. These conflicting findings highlight the need for further studies using novel, sensitive inflammatory markers such as SII and SIRI.\u003c/p\u003e\u003cp\u003eReducing perioperative inflammation in TKA is clinically important because excessive systemic inflammatory responses may delay wound healing, increase postoperative pain and opioid consumption, and contribute to complications such as infection or thromboembolic events. Understanding how anesthesia choice may influence these inflammatory changes could help guide perioperative management strategies.\u003c/p\u003e\u003cp\u003eThis study aimed to retrospectively compare perioperative changes in SII and SIRI in patients undergoing TKA under spinal versus general anesthesia, and to assess their association with opioid use, complications, and hospital stay.\u003c/p\u003e"},{"header":"Material and Method","content":"\u003cp\u003e Following ethical approval from the Clinical Research Ethics Committee of Tokat Gaziosmanpasa University (Approval No: 25-MOBAEK-160), this retrospective observational cohort study was conducted to evaluate patients who underwent total knee arthroplasty (TKA) between January 2020 and April 2025. The study was registered on ClinicalTrials.gov (Identifier: NCT06984315) on May 21, 2025, after data collection had been completed. Registration was performed retrospectively because the study, by design, was non-interventional and observational, and was initially considered exempt from prospective registration. The decision to register post hoc was made to enhance transparency and align with best practices in research reporting. All patient data were anonymized before analysis. Medical records were reviewed by two authors with access to the hospital\u0026rsquo;s electronic database. Although the reviewers were not blinded to group assignment, they adhered to predefined data abstraction criteria.\u003c/p\u003e\u003cp\u003e\u003cem\u003eEligibility Criteria\u003c/em\u003e\u003c/p\u003e\u003cp\u003eA total of 1,292 patients were screened using consecutive sampling. Of these, 443 were excluded for the following reasons: 74 underwent revision total knee arthroplasty (TKA), 83 had ASA physical status scores of III or higher, 233 lacked laboratory data, 18 had missing or incomplete clinical documentation, and 35 underwent conversion from spinal to general anesthesia due to failed neuraxial block. After applying these exclusion criteria, 849 patients met the eligibility requirements and were included in the final analysis. After applying all eligibility criteria, 849 patients were included in the final analysis. Inclusion criteria were age 18\u0026ndash;75 years and American Society of Anesthesiologists (ASA) physical status I\u0026ndash;II. Patients were excluded for any of the following: BMI\u0026thinsp;\u0026ge;\u0026thinsp;40 kg/m\u0026sup2;, ASA\u0026thinsp;\u0026ge;\u0026thinsp;III, significant cardiopulmonary or endocrine disease, chronic corticosteroid use, active infection, history of malignancy, intraoperative conversion of anesthesia type, emergency surgery, revision TKA, or incomplete laboratory or clinical records. Given the broad age range, baseline balance in age and other demographic variables was assessed statistically to ensure group comparability. Anesthesia type was not randomized; it was determined based on a combination of the patient\u0026rsquo;s clinical status and their individual preference, in consultation with the attending anesthesiologist.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData Collection\u003c/b\u003e\u003c/p\u003e\u003cp\u003eDemographic characteristics, clinical data, and laboratory values were extracted from patient records. Preoperative hemograms were obtained 1 day before surgery. Postoperative blood samples were included only if collected within the predefined 4\u0026ndash;12 hour postoperative window; patients lacking laboratory data within this interval were excluded. Inflammatory indices were calculated as: SII = (neutrophils \u0026times; platelets) / lymphocytes, SIRI = (neutrophils \u0026times; monocytes) / lymphocytes. Absolute changes (ΔSII, ΔSIRI) were defined as the absolute difference between postoperative and preoperative values. Total opioid consumption was recorded in morphine milligram equivalents (MME) within the first 24 hours postoperatively. Postoperative complications and hospital length of stay were also recorded.The primary outcomes of the study were absolute ΔSII and ΔSIRI. Secondary outcomes included total opioid consumption, length of hospital stay, and postoperative complications such as nausea, vomiting, and wound site infection. Patients were excluded if they had missing laboratory results, incomplete clinical documentation, or insufficient postoperative follow-up data.\u003c/p\u003e\u003cp\u003e\u003cb\u003eAnesthesia Protocols\u003c/b\u003e\u003c/p\u003e\u003cp\u003ePatients received either spinal anesthesia (Group S) or general anesthesia (Group G). In Group S, 3 mL of 0.5% hyperbaric bupivacaine was administered intrathecally at L3\u0026ndash;L4 or L4\u0026ndash;L5 with a 25G Quincke spinal needle. In Group G, induction included propofol (2 mg/kg), fentanyl (2 mcg/kg), and rocuronium (0.6 mg/kg), followed by endotracheal intubation and maintenance with sevoflurane (age-adjusted MAC of 1.0).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSurgical Technique\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAll surgeries were performed by one of three experienced orthopedic surgeons (coded as A, B, and E for anonymization), each with more than 10 years of clinical experience. The same standardized medial parapatellar approach was used across all procedures.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePostoperative Analgesia\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA standardized analgesic regimen was used across all patients. Scheduled intravenous paracetamol (1 g every 6 hours) and intramuscular diclofenac sodium (75 mg twice daily) were administered. Patients reporting a numeric rating scale (NRS) score\u0026thinsp;\u0026ge;\u0026thinsp;4 received intravenous tramadol as first-line rescue analgesia. If pain persisted, intravenous morphine (3 mg) was administered. Analgesia was administered by ward staff involved in postoperative care, who were aware of the anesthesia type. Due to the retrospective design and the routine clinical workflow, blinding was not applicable.\u003c/p\u003e\u003cp\u003eA post-hoc power analysis was conducted for the primary outcome variable (ΔSII), based on the observed Z value from the Mann-Whitney U test (Z = \u0026minus;\u0026thinsp;3.552) and total sample size (N\u0026thinsp;=\u0026thinsp;849). The corresponding effect size, calculated as the rank-biserial correlation coefficient, was r\u0026thinsp;=\u0026thinsp;0.122, indicating a small effect. Despite this, the analysis yielded a statistical power of approximately 82% (1\u0026thinsp;\u0026minus;\u0026thinsp;β\u0026thinsp;=\u0026thinsp;0.82) at an alpha level of 0.05, confirming that the sample size was sufficient to detect a significant difference in ΔSII between anesthesia groups.\u003c/p\u003e\u003cdiv id=\"Sec2\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eThe normality of continuous variables was assessed using the one-sample Kolmogorov-Smirnov test. Categorical variables were expressed as frequencies and percentages, while non-normally distributed continuous variables were presented as medians with interquartile ranges [median (IQR)]. Group comparisons for categorical variables were performed using the chi-square test. The Mann-Whitney U test was applied to compare preoperative and postoperative SII and SIRI values, ΔSII, ΔSIRI, and total opioid consumption between groups. Within-group comparisons of NLR, PLR, SII, and SIRI (pre- vs. postoperative) were conducted using the Wilcoxon signed-rank test for both the spinal (Group S) and general anesthesia (Group G) cohorts. In addition, multiple linear regression models were constructed to assess the association between anesthesia type and ΔSII/ΔSIRI, considering potential confounders such as age, sex, BMI, ASA class, comorbidities, surgical duration, and other relevant clinical or procedural factors. All analyses were performed using SPSS software (Version 20.0, SPSS Inc., Chicago, IL, USA), and a p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eOf the 1,292 patients initially screened for eligibility, 443 were excluded from the final analysis due to the following reasons: 74 underwent revision total knee arthroplasty, 83 had an ASA physical status classification of III or higher, 233 lacked perioperative laboratory data, 18 had missing or incomplete clinical documentation, and 35 experienced failed spinal anesthesia that required conversion to general anesthesia. As a result, 849 patients met all inclusion criteria and were included in the final analysis. The study's flow chart is in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median [interquartile range (IQR)] age of the patient population was 67 (61\u0026ndash;71) years and 83% were women. Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e demonstrates demographic data and descriptive characteristics of the patients in detail. No statistically significant differences were observed between the groups in terms of demographic variables and calculated preoperative inflammation indices (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline Characteristics and Clinical Outcomes of the Study Population\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup S\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGroup G\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67 (61 \u0026ndash; 72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e66 (61\u0026ndash;71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.31\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSex (Female / Male): n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e537 / 107 (83.4 / 16.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e167 / 38 (81.5 / 18.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.52\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28.93 (24.16\u0026ndash;30.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.65 (24.09\u0026ndash;30.11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.8 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASA Score: (I/II): n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e116 / 528 (18 / 82)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45 / 160 (22 / 78)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.21 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDuration of surgery (min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e120 (90 \u0026ndash; 120)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e120 (90 \u0026ndash; 120)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.19\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e137 (21.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41 (20)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.7 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e80 (12.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (10.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.4 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic heart disease: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e57 (8.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19 (9.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.9 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic lung Disease: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e79 (12.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24 (11.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.83 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThyroid disease: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39 (6.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17 (8.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.34 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCerebral vascular disease: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e41 (6.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.79 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNeoplasm: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (1.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (1.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.71 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRheumatic disease: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46 (7.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (4.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.21 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSmoking: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e60 (9.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e18 (8.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.93 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eINR (preoperative)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.05 (0.98\u0026ndash;1.14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.05 (0.97\u0026ndash;1.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.3\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNLR (preoperative)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.33 (1.64\u0026ndash;3.77)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.22 (1.59\u0026ndash;3.44)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.35\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLR (preoperative)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e127.75 (99.64\u0026ndash;170.85)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e128.33 (95.69\u0026ndash;172.76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.9\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSII (preoperatif)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e606.24 (419.72\u0026ndash;968.71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e555.7 (407.29\u0026ndash;1000.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.84\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSIRI (preoperatif)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.28 (0.86\u0026ndash;2.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.32 (0.78\u0026ndash;2.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.22\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e\u003csup\u003ea\u003c/sup\u003e Mann-Whitney U test; \u003csup\u003eb\u003c/sup\u003e Pearson Chi-Square test; Quantitative data are given as median [interquartile range (IQR)]\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003e(BMI: Body Mass İndex; ASA: American Society of Anesthesiologists; NLR: neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; SII: systemic immune inflammation index; SIRI: systemic inflammation response index)\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eThe median (IQR) ΔSII and ΔSIRI values for all patients were 1147.17 (517.69\u0026ndash;2261.74) and 3.96 (1.85\u0026ndash;7.28), respectively. Group G showed significantly higher ΔSII [1448.47 (677.78\u0026ndash;2670.86)] and ΔSIRI [4.56 (2.31\u0026ndash;9.23)] values compared to Group S [ΔSII: 1060.75 (463.69\u0026ndash;2093.28); ΔSIRI: 3.69 (1.70\u0026ndash;7.05)] (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001, p\u0026thinsp;=\u0026thinsp;0.002, respectively), (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003ePreoperative SII and SIRI values were similar between groups (p\u0026thinsp;=\u0026thinsp;0.84, p\u0026thinsp;=\u0026thinsp;0.22 respectively), as were preoperative NLR and PLR (p\u0026thinsp;=\u0026thinsp;0.35, p\u0026thinsp;=\u0026thinsp;0.9, respectively), (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIn contrast, postoperative values of SII, SIRI, NLR, and PLR were significantly higher in Group G compared to Group S (p\u0026thinsp;=\u0026thinsp;0.001, p\u0026thinsp;=\u0026thinsp;0.002, p\u0026thinsp;=\u0026thinsp;0.001, p\u0026thinsp;=\u0026thinsp;0.01, respectively), (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Corresponding median (IQR) values for postoperative SII were 2011.46 (1287.67\u0026ndash;3130.72) in Group G and 1649.36 (1041.93\u0026ndash;2801.83) in Group S; for SIRI: 4.56 (2.31\u0026ndash;9.23) and 3.69 (1.70\u0026ndash;7.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of some patients' outcomes in general and spinal anesthesia\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup S\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGroup G\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003er\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNLR (postoperative)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.25 (4.65\u0026ndash;10.97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.19 (5.57\u0026ndash;12.57)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003csup\u003ea\u003c/sup\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLR (postoperative)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e187.69 (127.16\u0026ndash;271.87)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e211.52 (143.23\u0026ndash;281.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003csup\u003ea\u003c/sup\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.088\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSII (postoperative)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1649.36 (1041.93\u0026ndash;2801.83)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2011.46 (1287.67\u0026ndash;3130.72)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003csup\u003ea\u003c/sup\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.113\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSIRI(postoperative)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.94 (2.76\u0026ndash;8.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5.67 (3.68\u0026ndash;10.46)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.002\u003csup\u003ea\u003c/sup\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.108\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eΔSII\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1060.75 (463.69\u0026ndash;2093.28)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1448.47 (677.78\u0026ndash;2670.86)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003ea\u003c/sup\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.122\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eΔSIRI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.69 (1.7\u0026ndash;7.05)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.56 (2.31\u0026ndash;9.23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.002\u003csup\u003ea\u003c/sup\u003e*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.122\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgeon (A / B / E): n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e241 / 215 / 188 (37.4 /33.4 / 29.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e74 / 66 / 65 (36.1 / 32.2 / 31.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.79 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgical duration (minute)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e120 (90 \u0026ndash; 120)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e120 (96\u0026ndash;120)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.19\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePostoperative total opioid consumed\u003c/p\u003e\u003cp\u003e(morphine milligram equivalents)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (5\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (5\u0026ndash;15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.134\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNausea: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e28 (4.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (5.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.35 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVomiting: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21 (3.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (4.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.51 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSurgical site infection: n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (0.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.68 \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal length of hospital stay (day)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (3\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (3\u0026ndash;4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.18\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003csup\u003ea\u003c/sup\u003e Mann-Whitney U test; \u003csup\u003eb\u003c/sup\u003e Chi-Square tes*; statistically significant; Quantitative data are given as median [interquartile range (IQR)]; r: Rank-biserial correlation coefficient. Calculated using the formula r\u0026thinsp;=\u0026thinsp;Z / \u0026radic;N, where Z is the test statistic from the Mann-Whitney U test and N is the total sample size.\u003c/p\u003e\u003cp\u003e(NLR: neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; SII: systemic immune inflammation index; SIRI: systemic inflammation response index; ΔSII = |SII (postoperatif) -SII (preoperatif)|; ΔSIRI = |SIRI (postoperatif) - SIRI (preoperatif)|; Surgeon A, B, and E refer to the anonymized identifiers of the three orthopedic surgeons who performed the procedures)\u003c/p\u003e\u003cp\u003eIn both groups, postoperative values of all inflammatory markers (SII, SIRI, NLR, and PLR) showed a significant increase compared to preoperative values (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001 for all), (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). These within-group elevations were observed consistently, regardless of anesthesia type. Figure\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents boxplots depicting these changes over time, enabling visual comparison of inflammatory marker dynamics between the spinal and general anesthesia groups.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eWilcoxon signed-ranks test; : statistically significant different from preoperative Group S; : statistically significant different from postoperative Group S; : statistically significant different from preoperative Group G; : statistically significant different from preoperative Group G.\u003c/p\u003e\u003cp\u003e(NLR: neutrophil lymphocyte ratio; PLR: platelet lymphocyte ratio; SII: systemic immune inflammation index; SIRI: systemic inflammation response index)\u003c/p\u003e\u003cp\u003eIn the multivariate linear regression analysis evaluating predictors of the absolute ΔSII, anesthesia type and ischemic heart disease emerged as statistically significant independent predictors. Patients who received general anesthesia exhibited a significantly greater increase in ΔSII compared to those who underwent spinal anesthesia (B\u0026thinsp;=\u0026thinsp;407.72, 95% CI: 151.60 to 663.84, p\u0026thinsp;=\u0026thinsp;0.002). In contrast, the presence of ischemic heart disease was associated with a significantly lower ΔSII (B = -716.06, 95% CI: -1189.44 to -242.69, p\u0026thinsp;=\u0026thinsp;0.003). Other demographic and clinical variables were not significantly associated with absolute ΔSII. Complete results of the regression model are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate Linear Regression Analysis for Predictors of the Absolute Change in Perioperative SII (ΔSII)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003eIndependent Variables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eUnstandardized Coefficients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eStandardized Coefficients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSig. (\u003cem\u003ep\u003c/em\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e95% Confidence Interval for B\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStd. Error\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLower Bound\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eUpper Bound\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnesthesia Type (Spinal / General)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e407.720\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e130.487\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.111\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.002*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e151.597\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e663.842\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"16\" rowspan=\"17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSex (Female / Male)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-68.299\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e148.262\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.645\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-359.312\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e222.714\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBMI (kg/m2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-6.387\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e16.271\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.695\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-38.323\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e25.549\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-21.053\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.879\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.089\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.078\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-38.482\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-3.624\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eASA Score: (I / II)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e235.727\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e152.136\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.059\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.122\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-62.889\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e534.343\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e42.324\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e146.951\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.773\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-246.116\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e330.764\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e46.334\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e175.423\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.792\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-297.992\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e390.659\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIschemic heart disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-716.063\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e241.170\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.130\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.003*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-1189.437\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-242.688\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChronic lung Disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e178.032\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e210.052\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.037\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.397\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-234.264\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e590.329\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThyroid disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-291.383\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e224.443\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.046\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.195\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-731.926\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e149.159\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCerebral vascular disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e174.163\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e250.249\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.027\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.487\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-317.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e665.358\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeoplasm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-201.383\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e408.490\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.622\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-1003.178\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e600.413\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRheumatic disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e72.013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e218.485\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.011\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.742\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-356.835\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e500.861\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e84.665\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e193.950\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.663\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-296.024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e465.355\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurgical duration (min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e3.695\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.467\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.051\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-1.147\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e8.537\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal opioid consumed (MME)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.237\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.130\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.039\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.274\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.981\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e3.454\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSII (preoperatif)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.101\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.065\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.054\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.119\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.026\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.228\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurgeon (B / E / Z)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-85.366\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e65.923\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.044\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.196\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-214.762\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e44.029\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMultiple Logistic Regression Analysis; Statistically significant results (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) are indicated with an asterisk (*)\u003c/p\u003e\u003cp\u003e(BMI\u0026thinsp;=\u0026thinsp;body mass index; MME\u0026thinsp;=\u0026thinsp;morphine milligram equivalent; SII\u0026thinsp;=\u0026thinsp;systemic immune inflammation index)\u003c/p\u003e\u003cp\u003eIn the multivariate linear regression analysis evaluating the predictors of the absolute ΔSIRI, anesthesia type and ischemic heart disease were found to be statistically significant independent predictors. Receiving general anesthesia was associated with a significantly higher increase in ΔSIRI compared to spinal anesthesia (B\u0026thinsp;=\u0026thinsp;1.150, 95% CI: 0.262 to 2.037, p\u0026thinsp;=\u0026thinsp;0.011). Conversely, the presence of ischemic heart disease was associated with a significantly lower ΔSIRI (B = -2.467, 95% CI: -4.121 to -0.813, p\u0026thinsp;=\u0026thinsp;0.004). Other variables did not show statistically significant associations with ΔSIRI. The full results of the regression analysis are presented in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eMultivariate Linear Regression Analysis for Predictors of the Absolute Change in Perioperative SIRI (ΔSIRI)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u003cp\u003eIndependent Variables\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eUnstandardized Coefficients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eStandardized Coefficients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSig.(\u003cem\u003ep\u003c/em\u003e)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e95% Confidence Interval for B\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eB\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStd. Error\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eBeta\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eLower Bound\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eUpper Bound\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnesthesia Type (Spinal / General)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.150\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.452\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.091\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.011*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.262\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e2.037\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"16\" rowspan=\"17\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSex (Female / Male)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-0.126\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.515\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.807\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-1.137\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.886\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBMI (kg/m2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.086\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.056\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.053\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.127\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.196\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-0.054\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.031\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.066\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.081\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.114\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eASA Score: (I / II)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.456\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.525\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.385\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.574\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e1.486\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.534\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.510\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.040\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.295\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.467\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e1.534\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eDiabetes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-0.229\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.606\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.014\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.705\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-1.418\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.960\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIschemic heart disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-2.467\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.843\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.130\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.004*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-4.121\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e-0.813\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eChronic lung Disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.321\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.727\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.080\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.070\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.106\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e20.747\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eThyroid disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-0.924\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.775\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.042\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.234\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-2.446\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.598\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCerebral vascular disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-0.059\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.865\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.946\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-1.756\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e1.639\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNeoplasm\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-1.179\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.411\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.029\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.403\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-3.948\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e1.590\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRheumatic disease\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.730\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.754\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.334\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.751\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e2.210\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSmoking\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-0.382\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.670\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.020\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.569\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-1.697\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.934\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurgical duration (min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.017\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.610\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.012\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.021\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTotal opioid consumed (MME)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.049\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.171\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e.0013\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSIRI (preoperatif)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.159\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.070\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.078\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.093\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.022\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.297\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSurgeon (B / E / Z)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e-0.200\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.228\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e-0.030\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.381\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e-0.648\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e\u003cp\u003e0.248\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eMultiple Logistic Regression Analysis; Statistically significant results (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) are indicated with an asterisk (*)\u003c/p\u003e\u003cp\u003e(BMI\u0026thinsp;=\u0026thinsp;body mass index; MME\u0026thinsp;=\u0026thinsp;morphine milligram equivalent; SIRI\u0026thinsp;=\u0026thinsp;systemic inflammation response index)\u003c/p\u003e\u003cp\u003eThere were no statistically significant differences between the groups in terms of the operating surgeon distribution or the duration of surgery (p\u0026thinsp;=\u0026thinsp;0.79 and p\u0026thinsp;=\u0026thinsp;0.19, respectively), indicating that intraoperative conditions were comparable across anesthesia types (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere were no statistically significant differences between groups regarding the distribution of operating surgeons or surgical duration (p\u0026thinsp;=\u0026thinsp;0.79 and p\u0026thinsp;=\u0026thinsp;0.90, respectively), (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), supporting the procedural consistency between groups.\u003c/p\u003e\u003cp\u003eThe median (IQR) postoperative total opioid consumed (MME) dose was 5 (5\u0026ndash;10) in Group S and 10 (5\u0026ndash;15) in Group G (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The total amount of opioids consumed postoperatively was significantly greater in Group G than in Group S (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001), (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eTo assess the clinical relevance of statistically significant differences, rank-biserial correlation coefficients (r) were calculated. Effect sizes were small across all comparisons: NLR (r\u0026thinsp;=\u0026thinsp;0.110), PLR (r\u0026thinsp;=\u0026thinsp;0.088), postoperative SII (r\u0026thinsp;=\u0026thinsp;0.113), postoperative SIRI (r\u0026thinsp;=\u0026thinsp;0.108), ΔSII (r\u0026thinsp;=\u0026thinsp;0.122), ΔSIRI (r\u0026thinsp;=\u0026thinsp;0.122), and total opioid consumption (r\u0026thinsp;=\u0026thinsp;0.134).\u003c/p\u003e\u003cp\u003ePostoperative complications were infrequent and comparable between groups. The most common adverse event was nausea, reported in 4.3% of patients in Group S and 5.9% in Group G (p\u0026thinsp;=\u0026thinsp;0.35). Vomiting occurred in 3.3% and 4.4% of patients, respectively (p\u0026thinsp;=\u0026thinsp;0.51). Surgical site infections were rare, observed in 0.8% of patients in Group S and 1.0% in Group G (p\u0026thinsp;=\u0026thinsp;0.68). All infections were classified as superficial and managed conservatively with antibiotics, without the need for surgical intervention. Among patients who developed infection, the median (IQR) length of hospital stay was 4 (3\u0026ndash;5) days, compared to 3 (3\u0026ndash;4) days in those without infection; however, this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.20), possibly due to the small number of cases and the mild nature of the infections. These events were transient and did not result in reoperation or substantial prolongation of hospitalization.\u003c/p\u003e\u003cp\u003eAn exploratory Spearman correlation analysis was performed to evaluate the relationship between inflammatory response and postoperative opioid consumption. The results demonstrated no statistically significant correlation between ΔSII and MME (r\u0026thinsp;=\u0026thinsp;0.058, p\u0026thinsp;=\u0026thinsp;0.09), or between ΔSIRI and MME (r\u0026thinsp;=\u0026thinsp;0.052, p\u0026thinsp;=\u0026thinsp;0.13). These findings suggest that the magnitude of the inflammatory response may not be directly associated with the amount of opioid required in the early postoperative period.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur findings suggest that spinal anesthesia may attenuate the systemic inflammatory response following TKA, as evidenced by significantly lower postoperative SII and SIRI values compared to general anesthesia.. Although the differences in ΔSII and ΔSIRI were statistically significant, further studies are needed to determine whether these changes translate into meaningful clinical outcomes.\u003c/p\u003e\u003cp\u003ePrevious studies have yielded conflicting results regarding the effect of anesthetic technique on systemic inflammatory response. Eroğlu et al. reported no significant differences in IL-6, IL-8, TNF-α, and CRP levels between spinal and general anesthesia in TKA patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Similarly, B\u0026uuml;y\u0026uuml;kocak et al. found comparable levels of IL-6, TNF-α, CRP, cortisol, and leptin in patients undergoing hemorrhoidectomy under either technique [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. On the other hand, other studies have demonstrated that regional techniques may mitigate inflammatory response. For instance, G\u0026uuml;ltekin et al. showed that epidural analgesia reduced perioperative SII increases in radical prostatectomy compared to general anesthesia alone [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Symeonidis et al. reported that spinal anesthesia led to a lower postoperative CRP rise than general anesthesia in open hernia repair [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and Žura et al. demonstrated that general anesthesia caused a greater increase in IL-2 levels compared to spinal anesthesia in transurethral prostate resection procedures [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eSII and SIRI are novel hematological markers derived from routine complete blood counts, reflecting the interplay between innate immunity and systemic inflammation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Due to their accessibility and cost-effectiveness, they have gained attention as practical alternatives to conventional biomarkers such as CRP, IL-6, IL-8, and TNF-α, which are more expensive and less feasible for routine use [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Several studies have demonstrated the prognostic utility of SII and SIRI across a range of clinical settings, including gastrointestinal and cardiovascular surgeries [\u003cspan additionalcitationids=\"CR4 CR5 CR6 CR7 CR8\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. While these findings support their broader clinical relevance, caution is warranted when extrapolating results to orthopedic procedures like TKA, given the differences in surgical stress and patient characteristics.\u003c/p\u003e\u003cp\u003eCompared to other hematologic indices like NLR and PLR, SII and SIRI have shown superior prognostic performance in various malignancies and systemic diseases [\u003cspan additionalcitationids=\"CR17 CR18 CR19\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Their reproducibility, low cost, and strong correlation with clinical outcomes make them promising tools for perioperative inflammatory monitoring, especially in large-scale or resource-limited settings.\u003c/p\u003e\u003cp\u003eRecent orthopedic studies have also explored clinical outcomes between spinal and general anesthesia in TKA. While some reported lower complication and readmission rates with spinal anesthesia [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], others, such as Stambough et al., emphasized that optimized general anesthesia protocols could yield comparable outcomes [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Our findings support the view that anesthetic technique may influence physiological parameters without necessarily affecting short-term clinical endpoints in lower-risk TKA patients. The lack of difference in complication rates and hospital stay may reflect the relatively low-risk profile of the study population (ASA I\u0026ndash;II), and the effectiveness of standardized perioperative care protocols.\u003c/p\u003e\u003cp\u003eMultiple logistic regression analysis revealed that general anesthesia was significantly associated with higher odds of increased perioperative SII and SIRI levels compared to spinal anesthesia, indicating a stronger systemic inflammatory response. Additionally, ischemic heart disease was independently associated with lower odds of elevated inflammatory indices. This inverse association aligns with findings from Ma and Li, who reported that higher SII levels were linked to a reduced prevalence of coronary artery disease in a large NHANES-based population [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These results may reflect immune adaptation or anti-inflammatory regulation in patients with chronic cardiovascular disease.\u003c/p\u003e\u003cp\u003eOne of the main limitations of this study is its retrospective design. Additionally, the study was conducted in a single center and included only patients with ASA physical status scores of I or II undergoing primary TKA. In higher-risk populations\u0026mdash;such as those with ASA III or greater and significant functional impairment\u0026mdash;perioperative systemic inflammatory responses may be more pronounced and clinically relevant. Another ilimitation is the lack of precise standardization in the timing of postoperative blood sampling. Although all samples were obtained within a consistent 4\u0026ndash;12-hour window, this variability may still have introduced minor fluctuations in inflammatory marker measurements. Future studies could benefit from fixed sampling intervals or time-adjusted analyses to address this issue. Finally, potential selection bias should be acknowledged. Anesthesia type was not randomized and may have been influenced by patient characteristics or clinician preference. Although key baseline variables such as ASA and BMI were statistically comparable between groups, residual confounding from unmeasured factors\u0026mdash;such as frailty, undiagnosed comorbidities, or provider discretion\u0026mdash;cannot be excluded. These limitations are inherent to the retrospective design and the lack of detailed covariate data.\u003c/p\u003e\u003cp\u003eProspective randomized controlled, multicenter studies involving more heterogeneous populations (including patients with ASA scores\u0026thinsp;\u0026ge;\u0026thinsp;III) are needed to evaluate the generalizability of these findings. In addition, studies that incorporate serial inflammatory marker measurements at standardized perioperative time points may offer deeper insights into the dynamics of systemic inflammation and its clinical implications.\u003c/p\u003e\u003cp\u003eIn conclusion, spinal anesthesia was associated with a milder systemic inflammatory response compared to general anesthesia in patients undergoing TKA. These findings support the hypothesis that spinal anesthesia may offer immunological advantages in TKA, particularly in patients where minimizing systemic inflammation is clinically desirable. However, due to the retrospective and observational nature of this study and the absence of differences in major clinical outcomes such as complication rates and hospital stay, spinal anesthesia cannot yet be definitively recommended as superior. Further prospective, randomized studies are necessary to validate these findings and better define the clinical implications of anesthesia choice in TKA.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by [Ali Genc], [Sezer Astan], [Mehtap Gürler Balta], [Vildan Kölükçü], [Ahmet Tuğrul Şahin], [Hakan Tapar] and [Tugba Karaman], [Serkan Karaman]. The first draft of the manuscript was written by [Ali Genc] and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval:\u003c/strong\u003e This retrospective study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Approval was granted by the Ethics Committee of Tokat Gaziosmanpaşa University (2025 / 25-MOBAEK-160).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial Registration:\u003c/strong\u003e The study was retrospectively registered on ClinicalTrials.gov with the registration number NCT06984315. At the time of study initiation, prospective registration was not deemed necessary due to its retrospective and non-interventional nature. The study was registered post hoc in the interest of transparency.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e: Waived, as the study involved anonymized retrospective data and individual patient consent was not required according to the guidelines of the Tokat Gaziosmanpasa University Clinical Research Ethics Committee.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e The data supporting the findings of this study are available from the corresponding author upon reasonable request. Interested researchers may contact the corresponding author via email and provide a brief description of their intended use.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBalta S, Celik T, Mikhailidis DP, Ozturk C, Demirkol S, Aparci M, Iyisoy A. 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Systemic immune-inflammation index predicts major adverse cardiovascular events in patients with ST-elevation myocardial infarction. Eur Heart J. 2021;42(Supplement1):ehab724.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChen JH, Zhai ET, Yuan YJ, Wu KM, Xu JB, Peng JJ, et al. Systemic immune-inflammation index for predicting prognosis of colorectal cancer. World J Gastroenterol. 2017;23(34):6261\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZhang Y, Xiao G, Wang R. Clinical significance of systemic immune-inflammation index (SII) and C-reactive protein-to-albumin ratio (CAR) in patients with esophageal cancer: a meta-analysis. Cancer Manag Res. 2019;11:4185\u0026ndash;200.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAgus HZ, Kahraman S, Arslan C, Yildirim C, Erturk M, Kalkan AK, Yildiz M. Systemic immune-inflammation index predicts mortality in infective endocarditis. J Saudi Heart Assoc. 2020;32(1):58\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu Z, Ge H, Miao Z, Shao S, Shi H, Dong C. Dynamic Changes in the Systemic Inflammation Response Index Predict the Outcome of Resectable Gastric Cancer Patients. Front Oncol. 2021;11:577043.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHeckmann ND, De A, Porter KR, Stambough JB. Spinal versus general anesthesia in total knee arthroplasty: are there differences in complication and readmission rates? J Arthroplasty. 2023;38(4):673\u0026ndash;9. e1.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eOwen AR, Amundson AW, Larson DR, Duncan CM, Smith HM, Johnson RL, et al. Spinal versus general anaesthesia in contemporary primary total knee arthroplasties. Bone Joint J. 2022;104(11):1209\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStambough JB, Bloom GB, Edwards PK, Mehaffey GR, Barnes CL, Mears SC. Rapid recovery after total joint arthroplasty using general anesthesia. J Arthroplasty. 2019;34(9):1889\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMa J, Li K. Systemic immune-inflammation index is associated with coronary heart disease: a cross-sectional study of NHANES 2009\u0026ndash;2018. Front Cardiovasc Med. 2023;10:1199433.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Inflammation, general anesthesia, spinal anesthesia, neutrophils, total knee arthroplasty, white blood cells","lastPublishedDoi":"10.21203/rs.3.rs-6810865/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6810865/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eIn total knee arthroplasty (TKA), both surgical trauma and the type of anesthesia administered can significantly affect systemic inflammation, which may influence postoperative recovery. This retrospective study aimed to compare perioperative changes in blood-derived systemic inflammatory markers\u0026mdash;specifically the systemic immune-inflammation index (SII) and the systemic inflammation response index (SIRI)\u0026mdash;in patients undergoing TKA under general versus spinal anesthesia.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis retrospective analysis included 849 patients who underwent elective primary TKA between January 2020 and April 2025. Inclusion criteria were age 18\u0026ndash;75 years and ASA physical status I\u0026ndash;II. Patients with BMI\u0026thinsp;\u0026ge;\u0026thinsp;40 kg/m\u0026sup2;, ASA\u0026thinsp;\u0026ge;\u0026thinsp;III, major comorbidities, active infection, revision surgery, or incomplete lab data were excluded. Patients were categorized into spinal anesthesia (Group S) and general anesthesia (Group G) groups. Pre- and postoperative hemograms were used to calculate SII and SIRI values; ΔSII and ΔSIRI were defined as absolute differences. Groups were compared in terms of inflammatory markers, total opioid requirement, postoperative complications, and hospital stay. Group comparability regarding age, ASA, and comorbidities was assessed, but no multivariate adjustment was performed due to the observational design.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of 849 patients were included in the study. The median ΔSII value was significantly higher in the general anesthesia group [Group G: 1448.47 (IQR: 677.78\u0026ndash;2670.86)] compared to the spinal anesthesia group [Group S: 1060.75 (IQR: 463.69\u0026ndash;2093.28); p\u0026thinsp;\u0026lt;\u0026thinsp;0.001]. Similarly, the ΔSIRI value was higher in Group G [4.56 (IQR: 2.31\u0026ndash;9.23)] than in Group S [3.69 (IQR: 1.70\u0026ndash;7.05); p\u0026thinsp;=\u0026thinsp;0.002]. The total opioid requirement within the first 24 postoperative hours was also significantly greater in Group G (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No statistically significant differences were found between the groups in terms of postoperative complication rates (p\u0026thinsp;=\u0026thinsp;0.48) or length of hospital stay (p\u0026thinsp;=\u0026thinsp;0.18).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eCompared to general anesthesia, spinal anesthesia was associated with a lower perioperative increase in systemic inflammatory blood markers in patients undergoing TKA. While no difference was observed in short-term clinical outcomes, these findings suggest that spinal anesthesia may offer an immunological advantage. Given the retrospective nature of the study, prospective research is warranted to determine whether these biomarker differences have meaningful clinical implications.\u003c/p\u003e","manuscriptTitle":"Comparison of Systemic Inflammatory Markers in Total Knee Arthroplasty Under Spinal vs General Anesthesia: A Retrospective Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-06 09:21:49","doi":"10.21203/rs.3.rs-6810865/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-08-29T07:39:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-08-17T18:18:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"131922159117850047873554026581698906148","date":"2025-08-17T04:57:43+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-08-15T04:55:50+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-08-08T09:25:33+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2025-08-03T08:12:30+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"5cae9977-4812-44eb-995c-a16f0764f35b","owner":[],"postedDate":"August 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-10-27T16:25:09+00:00","versionOfRecord":{"articleIdentity":"rs-6810865","link":"https://doi.org/10.1186/s12871-025-03399-y","journal":{"identity":"bmc-anesthesiology","isVorOnly":false,"title":"BMC Anesthesiology"},"publishedOn":"2025-10-22 16:16:24","publishedOnDateReadable":"October 22nd, 2025"},"versionCreatedAt":"2025-08-06 09:21:49","video":"","vorDoi":"10.1186/s12871-025-03399-y","vorDoiUrl":"https://doi.org/10.1186/s12871-025-03399-y","workflowStages":[]},"version":"v1","identity":"rs-6810865","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6810865","identity":"rs-6810865","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}