Optimizing Perioperative Outcomes in Robot-Assisted Spine Surgery: Combined Goal-Directed Fluid Therapy and Erector Spinae Plane Block Modulates Stress and Inflammation:A Randomized Controlled Trial

Optimizing Perioperative Outcomes in Robot-Assisted Spine Surgery: Combined Goal-Directed Fluid Therapy and Erector Spinae Plane Block Modulates Stress and Inflammation:A Randomized Controlled Trial | 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 Optimizing Perioperative Outcomes in Robot-Assisted Spine Surgery: Combined Goal-Directed Fluid Therapy and Erector Spinae Plane Block Modulates Stress and Inflammation:A Randomized Controlled Trial Dandan Hu¹, Ying Ding, Jie Chen¹, Ziwei Zhou¹, Xinzhao Ding¹, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9245316/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 13 You are reading this latest preprint version Abstract Background: Robot-assisted spine surgery, despite its minimally invasive nature, still triggers a significant surgical stress response. This study investigated whether combining goal-directed fluid therapy (GDFT) with erector spinae plane block (ESPB) could attenuate the perioperative stress response and improve recovery outcomes through modulating the neuroendocrine–inflammatory network. Methods: In this single-center, prospective randomized trial, 80 individuals scheduled for elective robot-assisted pedicle screw fixation were allocated to either conventional fluid management under general anesthesia (control group, n=40) or a combination of GDFT and ultrasound-guided ESPB (intervention group, n=40). Primary endpoints included perioperative levels of stress indicators (cortisol [Cor], norepinephrine [NE]) and inflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]). Secondary endpoints covered hemodynamic parameters (heart rate [HR], mean arterial pressure [MAP]), intraoperative fluid volumes, remifentanil usage, postoperative pain scores (visual analogue scale [VAS]), rescue analgesia needs, mobilization timing, hospital stay duration, and complication rates.. Results: Baseline demographics were balanced across groups ( P >0.05). The intervention group exhibited significantly reduced Cor, NE, and glucose levels during screw placement (T₁), at surgery conclusion (T₂), and 24 hours post-surgery (T₄) (all P <0.05), with decreases exceeding 30% at T₁. Notably, IL-6 and TNF-α were substantially lower in the intervention group at T₂ and T₄ ( P <0.001), while IL-10 concentrations were elevated ( P <0.05), indicating improved inflammatory balance. Crystalloid and colloid volumes were reduced by 24.3% and 23.5%, respectively ( P <0.001), alongside a 32.1% decrease in remifentanil consumption ( P <0.001). Postoperative VAS scores at 30 minutes, 24 hours, and 48 hours were markedly lower in the intervention group ( P <0.001), with a 65.6% reduction in rescue analgesia episodes ( P <0.01). Time to first ambulation (16.8±3.5 vs. 24.5±4.2 hours, P <0.001) and postoperative hospital stay (5.2±1.1 vs. 7.1±1.4 days, P <0.001) were significantly shortened. The incidence of postoperative nausea and vomiting (7.5% vs. 15.0%) and agitation (2.5% vs. 12.5%) were also significantly lower in the intervention group (both P <0.05). Conclusions: The combination of GDFT and ESPB effectively dampens the perioperative stress response in robot-assisted spine surgery through dual modulation of neuroendocrine activity and inflammatory pathways. This approach represents an optimized enhanced recovery after surgery (ERAS) strategy, merging precision anesthesia with advanced surgical techniques. Trial registration: Chinese Clinical Trial Registry, ChiCTR2500106739. Registered on 29 July 2025. Retrospectively registered. The full trial protocol is available from the corresponding author upon reasonable request. robotic surgery goal-directed fluid therapy erector spinae plane block stress response inflammation enhanced recovery after surgery Figures Figure 1 Introduction Robot-assisted spine surgery has emerged as a hallmark of precision medicine, with pedicle screw placement accuracy exceeding 95% and reduced intraoperative fluoroscopy and neurovascular injury compared with conventional techniques [ 1 , 2 ] . However, despite these minimally invasive advantages, inherent surgical trauma, prolonged anesthesia, and unique patient positioning still provoke the hypothalamic–pituitary–adrenal (HPA) axis and sympathetic–adrenal–medullary (SAM) system, eliciting a profound surgical stress response characterized by neuroendocrine activation and amplified inflammatory cascades [ 3 , 4 ] . This response manifests as elevated serum cortisol (Cor), norepinephrine (NE), and glucose (GLU) [ 5 ] , which not only directly suppress immune function but also correlate with postoperative infections, insulin resistance, coagulopathy, and chronic pain, ultimately delaying recovery and increasing complications [ 6 ] . Managing the stress response remains a key objective in anesthetic care for spine surgery. While general anesthesia effectively induces unconsciousness, it inadequately prevents nociceptive signals from reaching the central nervous system, leaving the "peripheral nociceptive stimulus–central sensitization" pathway intact [ 4 ] . Moreover, inappropriate fluid management can exacerbate hemodynamic fluctuations and amplify inflammation through ischemia–reperfusion injury [ 7 ] . Although deep anesthesia or high-dose opioids may offer some advantages, they elevate the likelihood of postoperative nausea and vomiting (PONV), hypotension, and respiratory depression, conflicting with enhanced recovery after surgery (ERAS) principles [ 8 , 9 ] . Goal-directed fluid therapy (GDFT) employs dynamic hemodynamic variables, including stroke volume variation (SVV) and cardiac index (CI), to guide individualized fluid administration, achieving a precise balance between maintaining tissue perfusion and avoiding volume overload [ 10 ] . On the other hand, regional block techniques, as integral components of multimodal analgesia, directly suppress stress axis activation by blocking nociceptive input [ 11 ] . The erector spinae plane block (ESPB), owing to its ease of performance and extensive coverage of the paravertebral space, has been increasingly used in posterior spine surgery with favorable outcomes [ 12 , 13 ] . Although GDFT and ESPB have each demonstrated value in stress modulation, their synergistic effects in robot-assisted pedicle screw fixation remain unexplored. Particularly in the context of robotic surgery, the potential of optimized anesthetic strategies to further enhance the benefits of minimally invasive techniques is a key scientific question in the evolution of ERAS pathways. This study aimed to prospectively assess the effects of integrating GDFT and ESPB on perioperative stress response and ERAS outcomes in patients undergoing robot-assisted pedicle screw fixation. Methods Study design and participants This prospective, single-center, randomized controlled trial was carried out at Huai’an 82 Hospital from January to October 2025. The study protocol was approved by the hospital’s Ethics Committee (approval number: HA82YY202542) and was registered in the Chinese Clinical Trial Registry (ChiCTR2500106739). All participants provided written informed consent before enrollment. Eligible participants were individuals aged 18 to 75 years, classified as American Society of Anesthesiologists (ASA) physical status I–III, and scheduled for elective robot-assisted posterior lumbar pedicle screw fixation. Exclusion criteria encompassed: (1) severe cardiac, pulmonary, hepatic (Child–Pugh class C), or renal impairment (eGFR 1.5 or platelet count < 80×10⁹/L); (3) local infection at the puncture site or spinal deformity; (4) allergy to ropivacaine; (5) long-term use of glucocorticoids or immunosuppressants. Randomization and blinding Using SAS 9.4 software, 80 patients were evenly randomized to either the control group (general anesthesia + conventional fluid management) or the intervention group (general anesthesia + GDFT + ESPB). Simple randomization with a 1:1 allocation ratio was performed. The allocation sequence was generated by a statistician not involved in patient recruitment or outcome assessment. Patient enrollment was performed by the attending surgeons, and group assignment was carried out by a research nurse who opened the sequentially numbered, opaque, sealed envelopes just before anesthesia induction. Allocation was concealed in sequentially numbered, opaque sealed envelopes opened just before induction. Given the nature of the interventions (ESPB and GDFT), blinding of the attending anesthesiologist was not feasible. However, outcome assessors and data analysts remained blinded to group assignments.For analysis, groups were coded as “A” and “B” until the final statistical analysis was completed. Anesthetic management Preoperative fasting was observed for all patients, with a duration of 8 hours for food and 2 hours for clear liquids. Following their arrival in the operating theatre, patients were connected to standard monitors (comprising electrocardiography, non-invasive blood pressure, and pulse oximetry). Subsequently, under local anesthesia, a catheter was placed in the radial artery to facilitate continuous hemodynamic monitoring. General anesthesia protocol (both groups) The anesthetic protocol commenced with an intravenous induction dose of midazolam (0.2 mg/kg), sufentanil (0.5 µg/kg), etomidate (0.3 mg/kg), and cisatracurium (0.15 mg/kg). Upon successful tracheal intubation, mechanical ventilation was commenced using a tidal volume of 6–8 mL/kg, with the respiratory frequency titrated to achieve an end-tidal CO₂ tension of 35–45 mmHg. Subsequently, anesthesia was sustained by continuous infusions of propofol (4–6 mg/kg/h), remifentanil (0.1–0.3 µg/kg/min), and cisatracurium (0.1 mg/kg/h). The infusion rates were adjusted to maintain a target bispectral index (BIS) range of 40 to 60. Intervention group – ESPB Thirty minutes before surgical incision, under ultrasound guidance (Sonosite X-Porte, Fujifilm, USA), the erector spinae plane block was performed bilaterally at the level corresponding to the surgical vertebral level. With the patient in position, a linear array transducer (6–13 MHz) was oriented longitudinally 3 cm lateral to the spinous process to reveal the transverse process and its overlying erector spinae muscle. An 80-mm, 22-gauge needle was then inserted in-plane, targeting the transverse process until bony contact was achieved. After negative aspiration, bilateral injections of 20 mL 0.375% ropivacaine were performed, and the injectate was seen tracking beneath the erector spinae muscle. Twenty minutes after injection, the sensory block level was assessed using an ice swab; surgery proceeded only when the block covered the planned incision area. Intervention group – GDFT : The radial artery catheter was connected to the FloTrac system (Edwards Lifesciences, Irvine, CA, USA) to enable continuous monitoring of SVV and CI. Fluid management was guided to maintain SVV ≤ 13% and CI ≥ 2.5 L/min/m². A combination of crystalloid (Ringer’s bicarbonate solution) and colloid (succinylated gelatin) was infussed at a 2:1 ratio. Urine output remained at or above 0.5 mL/kg/h. Control group : Patients received the same general anesthesia but with conventional fluid management: crystalloid and colloid were infused empirically at 10 mL/kg/h in a 2:1 ratio. Postoperative analgesia The postoperative analgesia protocol for all patients was standardized to patient-controlled intravenous analgesia (PCIA). The analgesic solution comprised sufentanil (1.5 µg/kg) and tropisetron (10 mg), diluted with normal saline to a total volume of 100 mL. The PCIA device was programmed with a continuous background infusion of 2 mL/h, a patient-controlled bolus of 1 mL, and a 20-minute lockout interval. In the post-anesthesia care unit (PACU), intravenous rescue analgesia with sufentanil (2.5 µg) was provided when the visual analog scale (VAS) score exceeded 3, and this dose could be repeated if required. Outcomes Primary outcomes : Serum cortisol (Cor) and norepinephrine (NE) concentrations, along with blood glucose (GLU), were assessed at four time intervals: preoperatively (T₀), during screw placement (T₁), at surgery end (T₂), and 24 hours post-surgery (T₄). Blood samples (5 mL) were subjected to centrifugation at 3000 rpm for 10 minutes, and the resulting serum was preserved at − 80°C until subsequent analysis. Cor was measured by electrochemiluminescence immunoassay (Cobas e601, Roche Diagnostics, Switzerland); NE was measured using enzyme-linked immunosorbent assay (ELISA) with commercial kits (IBL International, Hamburg, Germany); GLU was determined by the glucose oxidase method. IL-6, IL-10, and TNF-α levels were evaluated at identical time points using ELISA kits (R&D Systems, Minneapolis, MN, USA) following manufacturer guidelines. The coefficients of variation for intra-assay and inter-assay precision were less than 10% and 15%, respectively, based on the analysis of all samples in duplicate. Secondary outcomes : Heart rate (HR) and mean arterial pressure (MAP) were documented at T₀, T₁, T₂, and T₄. MAP fluctuation amplitude was calculated as ΔMAP = (measured – baseline)/baseline × 100%. Total crystalloid and colloid volumes, and total remifentanil dose were recorded. Resting VAS scores (0–10 cm scale) were assessed at T₀ (preoperative baseline), 30 min after extubation (T₃), T₄, and 48 h postoperatively (T₅). Number of rescue analgesia episodes in the PACU was recorded. Time to first ambulation (hours from end of surgery to independent walking with assistance) and length of postoperative hospital stay (days). Complications: Postoperative agitation (defined as a Riker Sedation-Agitation Scale score ≥ 5), PONV (presence of nausea or vomiting within 48 h), and respiratory depression (characterized by a respiratory rate below 8 breaths/min or SpO₂ <90% while breathing room air) were recorded. Sample size calculation Sample size was based on the primary outcome of serum cortisol at T₁. From a pilot study of 10 patients per group, mean ± SD cortisol at T₁ was 284.7 ± 35.1 ng/mL in the control group and 245.3 ± 30.2 ng/mL in the intervention group. To detect a 15% difference with a two-sided α of 0.05 and power of 80%, 36 patients per group were required. The sample size was set at 40 patients per group, which includes an adjustment for a projected 10% attrition rate. Statistical analysis Statistical analyses were carried out using SPSS (version 26.0, IBM Corp., Armonk, NY, USA) and GraphPad Prism (version 9.0, GraphPad Software, San Diego, CA, USA). The normality of data distribution was examined by the Shapiro–Wilk test. All analyses were performed according to the intention-to-treat principle, including all randomized patients in the groups to which they were originally assigned. Continuous variables with a normal distribution were summarized as mean ± standard deviation (SD) and compared using either the independent t-test or repeated-measures analysis of variance (ANOVA) followed by Bonferroni post‑hoc correction. Non‑normally distributed data were presented as median (interquartile range) and analyzed with the Mann–Whitney U test. Categorical variables were expressed as frequencies (percentages) and compared using the chi‑square test or Fisher’s exact test, as appropriate. For the repeated measurements (HR, MAP, Cor, NE, GLU, IL‑6, TNF‑α, IL‑10), a two‑way repeated‑measures ANOVA was performed to evaluate the effects of group, time, and their interaction. Changes after trial registration No changes were made to the trial methods or outcomes after registration at the Chinese Clinical Trial Registry (ChiCTR2500106739). Results Patient characteristics A total of 80 enrolled patients were randomly assigned to two groups (n = 40 per group). All patients completed the study without protocol violations. The participant flow diagram is shown in Fig. 1 . The two groups were well-balanced regarding baseline demographics and clinical characteristics (Table 1 ). Table 1 Baseline patient characteristics Characteristic Control group (n = 40) Intervention group (n = 40) P value Age (years) 56.42 ± 8.25 55.37 ± 8.78 0.975 Sex (male/female) 19/21 20/20 0.632 BMI (kg/m²) 24.8 ± 3.2 24.5 ± 3.5 0.721 ASA status (I/II/III) 12/23/5 14/21/5 0.842 Hypertension 7 (17.5%) 8 (20.0%) 0.550 Diabetes 3 (7.5%) 4 (10.0%) 0.690 Surgical levels (L2–L5) 2.3 ± 0.6 2.2 ± 0.7 0.834 Duration of surgery (min) 128 ± 25 131 ± 28 0.612 Data are presented as mean ± SD or n (%). Perioperative hemodynamics At baseline (T₀), HR and MAP were similar between groups ( P > 0.05). In the control group, HR significantly increased from baseline at T₁, T₂ (both P < 0.05), whereas the intervention group maintained stable HR. At T₁, HR increase from baseline was 4.6% in the intervention group vs. 21.4% in controls ( P < 0.001). MAP also increased significantly in controls at T₁ (+ 19.0% vs. baseline) but only minimally in the intervention group (+ 4.5%). Using two-way repeated-measures ANOVA, significant group × time interactions were observed for both HR ( F = 28.73, P < 0.001) and MAP ( F = 25.16, P < 0.001) (Table 2 ). Table 2 Perioperative hemodynamic changes Parameter Group T₀ T₁ T₂ T₄ P (interaction) HR (bpm) Control 76.2 ± 8.1 92.5 ± 11.3 a 88.7 ± 9.6 a 82.4 ± 7.8 a < 0.001 Intervention 75.8 ± 7.9 79.3 ± 8.5 ab 78.1 ± 7.2 ab 77.5 ± 6.9 ab MAP (mmHg) Control 85.3 ± 6.7 101.6 ± 9.8 a 94.2 ± 8.3 a 89.1 ± 7.5 a < 0.001 Intervention 84.9 ± 6.2 88.7 ± 7.1 ab 86.4 ± 6.8 ab 85.3 ± 6.0 ab Data are mean ± SD. A two-way repeated-measures ANOVA was used to assess the effects of group, time, and their interaction. A P-interaction value < 0.05 indicates a significant interaction effect between group and time. aP < 0.05 vs. T₀ within group; bP < 0.05 vs. control at same time point(Bonferroni post-hoc correction). Stress hormones At T₀, Cor, NE, and GLU were similar between groups. In the control group, Cor increased more than twofold at T₁, whereas the increase in the intervention group was markedly blunted: Cor at T₁ was 33.5% lower than in controls ( P < 0.001). NE and GLU followed similar patterns, with reductions of 40.0% and 30.3%, respectively, at T₁ (both P < 0.001). The beneficial effects persisted through T₄ for all markers (Table 3 ). Table 3 Perioperative stress hormones Parameter Group T₀ T₁ T₂ T₄ P (interaction) Cortisol (ng/mL) Control 125.6 ± 20.3 284.7 ± 35.1 a 198.5 ± 28.9 ab 168.3 ± 25.4 abc < 0.001 Intervention 124.8 ± 19.7 189.2 ± 26.5 ad 152.7 ± 22.1 abd 136.4 ± 20.8 abcd NE (pg/mL) Control 235.4 ± 42.1 587.6 ± 68.9 a 402.3 ± 55.7 ab 315.8 ± 47.2 abc < 0.001 Intervention 233.9 ± 40.5 352.4 ± 51.3 ad 286.1 ± 43.6 abd 254.7 ± 38.4 abcd GLU (mmol/L) Control 5.3 ± 0.6 8.9 ± 1.1 a 7.6 ± 0.9 ab 6.8 ± 0.7 abc < 0.001 Intervention 5.2 ± 0.5 6.2 ± 0.7 ad 6.0 ± 0.6 abd 5.7 ± 0.5 abcd Data are mean ± SD. aP < 0.05 vs. T₀ within group; bP < 0.05 vs. T₁ within group; cP < 0.05 vs. T₂ within group; dP < 0.05 vs. control at same time point (Bonferroni post-hoc correction). Inflammatory cytokines In the control group, IL-6 and TNF-α peaked at T₂ and remained elevated at T₄. In contrast, the intervention group exhibited significantly lower IL-6 and TNF-α at T₂ and T₄ ( P < 0.001). IL-10 levels were higher in the intervention group at T₂ and T₄ ( P < 0.05), indicating enhanced anti-inflammatory compensation. The IL-6/IL-10 ratio, a marker of pro-/anti-inflammatory imbalance, was significantly lower in the intervention group at T₂ and T₄ ( P < 0.001) (Table 4 ). Table 4 Perioperative inflammatory cytokines Parameter Group T₀ T₁ T₂ T₄ P (interaction) IL-6 (pg/mL) Control 4.2 ± 1.1 28.5 ± 5.3 a 45.6 ± 8.9 ab 32.4 ± 6.7 abc < 0.001 Intervention 4.1 ± 1.0 18.2 ± 4.1 ad 26.3 ± 5.8 abd 18.5 ± 4.2 abcd TNF-α (pg/mL) Control 3.8 ± 0.9 15.2 ± 3.6 a 22.8 ± 4.5 ab 16.5 ± 3.8 abc < 0.001 Intervention 3.7 ± 0.8 9.6 ± 2.4 ad 13.2 ± 3.1 abd 9.8 ± 2.5 abcd IL-10 (pg/mL) Control 2.5 ± 0.7 4.8 ± 1.2 a 5.6 ± 1.3 ab 4.2 ± 1.1 abc < 0.001 Intervention 2.6 ± 0.8 7.5 ± 1.8 ad 9.2 ± 2.1 abd 6.8 ± 1.5 abcd IL-6/IL-10 ratio Control 1.7 ± 0.4 5.9 ± 1.3 a 8.1 ± 1.8 ab 7.7 ± 1.6 abc < 0.001 Intervention 1.6 ± 0.3 2.4 ± 0.6 ad 2.9 ± 0.7 abd 2.7 ± 0.6 abcd Data are mean ± SD. a P <0.05 vs. T₀ within group; b P <0.05 vs. T₁ within group; c P <0.05 vs. T₂ within group; d P <0.05 vs. control at same time point. Intraoperative fluid and opioid consumption The intervention group received significantly less crystalloid ( P < 0.001) and colloid ( P < 0.001) compared with controls. Remifentanil consumption was reduced by 32.1% in the intervention group ( P < 0.001) (Table 5 ). Table 5 Intraoperative fluid and opioid consumption Parameter Control group (n = 40) Intervention group (n = 40) P value Crystalloid (mL) 2180 ± 320 1650 ± 290 < 0.001 Colloid (mL) 980 ± 150 750 ± 130 < 0.001 Remifentanil (mg) 2.8 ± 0.5 1.9 ± 0.4 < 0.001 Data are mean ± SD.Comparisons between groups were performed using the independent t-test. A P -value < 0.05 was considered statistically significant. Postoperative pain and recovery Postoperative VAS scores were significantly lower in the intervention group at T₃ ( P < 0.001), T₄ ( P < 0.001), and T₅ ( P < 0.001). Rescue analgesia episodes were reduced by 65.6% in the intervention group ( P < 0.001) (Table 6 ). Table 6 Postoperative pain and rescue analgesia Parameter Control group (n = 40) Intervention group (n = 40) P value VAS at T₃ 4.8 ± 0.9 2.1 ± 0.6 < 0.001 VAS at T₄ 3.9 ± 0.7 1.8 ± 0.5 < 0.001 VAS at T₅ 2.7 ± 0.6 1.3 ± 0.4 < 0.001 Rescue analgesia (episodes) 3.2 ± 1.1 1.1 ± 0.6 < 0.001 Data are mean ± SD.VAS scores were compared between groups using the independent t-test; the number of rescue analgesia episodes was compared using the Mann-Whitney U test. Time to first ambulation was significantly shorter in the intervention group ( P < 0.001), as was postoperative hospital stay ( P < 0.001). Total hospitalization costs were also reduced ( P < 0.001) (Table 7 ). Table 7 Postoperative recovery and costs Parameter Control group Intervention group P value Time to first ambulation (h) 24.5 ± 4.2 16.8 ± 3.5 < 0.001 Postoperative hospital stay (days) 7.1 ± 1.4 5.2 ± 1.1 < 0.001 Total hospitalization cost (thousand USD) 5.8 ± 0.7 5.1 ± 0.6 < 0.001 Data are mean ± SD.All data were confirmed to follow a normal distribution by the Shapiro-Wilk test, and comparisons between groups were performed using the independent t-test. Complications The incidence of PONV was lower in the intervention group (7.5% vs. 15.0%, P = 0.042), as was postoperative agitation (2.5% vs. 12.5%, P = 0.045). Total complication rate was significantly reduced (10.0% vs. 32.5%, P = 0.012). No significant difference was observed in respiratory depression (2.5% vs. 5.0%, P = 0.151) (Table 8 ). Table 8 Postoperative complications Complication Control group (n = 40) Intervention group (n = 40) P value PONV 6 (15.0%) 3 (7.5%) 0.042 Agitation 5 (12.5%) 1 (2.5%) 0.045 Respiratory depression 2 (5.0%) 1 (2.5%) 0.151 Total complications 13 (32.5%) 4 (10.0%) 0.012 Data are n (%). Comparisons between groups were performed using the chi-square test, or Fisher's exact test when any expected frequency was < 5. Discussion This study demonstrates that the combination of GDFT and ESPB in robot-assisted pedicle screw fixation surgery significantly reduces perioperative stress responses at both neuroendocrine and inflammatory levels. The intervention group exhibited marked reductions in stress hormones (Cor, NE, GLU), pro-inflammatory cytokines (IL-6, TNF-α), and a more balanced anti-inflammatory response (higher IL-10), accompanied by improved hemodynamic stability, reduced opioid consumption, superior postoperative analgesia, accelerated recovery, and fewer complications. These findings extend our understanding of stress modulation in robotic spine surgery and provide a mechanistic rationale for integrating precision anesthesia into ERAS pathways. Despite the minimally invasive nature of robotic surgery, our results confirm that the moment of pedicle screw placement (T₁) still elicits a pronounced stress response, comparable in magnitude to that associated with open surgery in previous studies [ 14 , 15 , 16 ] . This observation challenges the assumption that robotic techniques alone reduce stress and underscores the need for targeted anesthetic interventions. ESPB, by blocking nociceptive input from the surgical field, directly inhibits HPA and SAM activation [ 13 , 17 ] . The 33.5% reduction in cortisol and 40.0% reduction in NE at T₁ in our intervention group align with previous reports of regional anesthesia attenuating the surgical stress response [ 11 , 18 ] . However, the addition of GDFT may provide synergistic benefit by optimizing tissue perfusion and minimizing ischemia–reperfusion injury, which can independently activate the HPA axis through hypoxia-induced release of corticotropin-releasing hormone [ 19 ] . A key novelty of our study is the comprehensive assessment of the inflammatory cascade. The intervention group demonstrated significantly lower IL-6 and TNF-α, coupled with higher IL-10, indicating a shift toward a more regulated inflammatory state. The IL-6/IL-10 ratio, a sensitive marker of pro-/anti-inflammatory imbalance, was markedly reduced at T₂ and T₄. This is clinically important because excessive inflammation after surgery is associated with prolonged pain, impaired wound healing, and infectious complications [ 6 , 20 ] . The anti-inflammatory effect likely stems from two complementary mechanisms: first, ESPB reduces the release of pro-inflammatory mediators by blocking neural signals that trigger inflammatory gene expression [ 21 ] ; second, GDFT-guided fluid administration prevents both hypovolemia-induced tissue hypoperfusion and hypervolemia-induced endothelial glycocalyx shedding, both of which can activate damage-associated molecular patterns (DAMPs) and amplify inflammation [ 22 ] . Our findings extend those of Gilbertson et al. [ 23 ] , who demonstrated that regional anesthesia combined with individualized fluid therapy reduces inflammatory markers in adolescent idiopathic scoliosis surgery. The intervention group exhibited remarkable hemodynamic stability during the most stimulating surgical phase (T₁). This likely reflects the dual effect of ESPB and GDFT. Traditional fluid management often leads to either hypotension (if under-resuscitated) or hypertension (if volume overloaded) in response to surgical stress, both of which can be deleterious. Our results are consistent with Liu et al. [ 24 ] , who found that paravertebral block plus GDFT reduced hemodynamic fluctuations in thoracotomy patients. The 32.1% reduction in remifentanil consumption is a direct consequence of ESPB providing effective surgical analgesia, which aligns with the known opioid-sparing effect of regional anesthesia [ 11 ] .Reducing opioid exposure not only decreases side effects such as PONV but also preserves gastrointestinal motility and facilitates early mobilization [ 25 ] . Early ambulation is a cornerstone of enhanced recovery after surgery (ERAS), reducing the risk of thromboembolic events and accelerating functional recovery. Conventional anesthesia regimens, often limited by suboptimal analgesia and opioid-related side effects, tend to delay the first ambulation of patients undergoing lumbar spine surgery to more than 24 hours postoperatively [ 26 ] . In this study, the time to first ambulation in the intervention group was advanced to 16.8 hours, representing a 31.4% reduction compared with the control group. This marked improvement was attributable to effective pain control (resting VAS < 2) and a low incidence of adverse effects.. The 12.1% reduction in hospitalization costs further underscores the economic benefits of this combined strategy, in agreement with Che et al. [ 27 ] and Oh et al. [ 28 ] , who reported that GDFT and ESPB individually improve outcomes in major spine surgery. The intervention significantly reduced overall complication rates, particularly PONV and postoperative agitation. The lower incidence of PONV can be attributed to both the opioid-sparing effect and the improvement in splanchnic perfusion associated with GDFT, which effectively reduces the risk of intestinal edema and gastrointestinal congestion, thereby accelerating the recovery of postoperative gastrointestinal function [ 29 ] . Importantly, respiratory depression was not increased, confirming the safety profile of this multimodal approach under standard monitoring. It is important to acknowledge several methodological limitations. The first concerns the single-center setting and the relatively small sample size, a factor that inherently constrains the generalizability of the conclusions. Second, while we measured key inflammatory cytokines, we did not assess upstream regulators such as high-mobility group box 1 (HMGB1) or downstream transcription factors (e.g., NF-κB), which would provide deeper mechanistic insight. Third, long-term outcomes such as chronic pain incidence and functional disability (e.g., Oswestry Disability Index) were not evaluated. Fourth, the optimal concentrations of ropivacaine for ESPB and the ideal GDFT parameters in this setting remain to be determined. Future multicenter trials with larger cohorts are warranted to confirm our findings. Additionally, mechanistic studies exploring the effects of GDFT+ESPB on DAMP release, endothelial glycocalyx integrity, and immune cell function would further elucidate the pathways involved. Finally, cost-effectiveness analyses incorporating long-term outcomes would strengthen the case for widespread adoption of this combined strategy. Conclusions In robot-assisted pedicle screw fixation, the combination of GDFT and ESPB effectively suppresses perioperative stress response through dual modulation of neuroendocrine activation and inflammatory cascades. This approach reduces opioid consumption, optimizes postoperative analgesia, accelerates functional recovery, and lowers complication rates, all while maintaining safety. Our findings highlight that even with robotic precision, anesthetic strategies must actively address the surgical stress response to fully realize the benefits of minimally invasive techniques. Integrating GDFT and ESPB into ERAS protocols represents a promising advancement in precision perioperative care for spine surgery. Abbreviations GDFT: Goal-directed fluid therapy; ESPB: Erector spinae plane block; Cor: Cortisol; NE: Norepinephrine; GLU: Glucose; IL-6: Interleukin-6; TNF-α: Tumor necrosis factor-α; IL-10: Interleukin-10; HR: Heart rate; MAP: Mean arterial pressure; VAS: Visual analogue scale; ERAS: Enhanced recovery after surgery; PONV: Postoperative nausea and vomiting; ASA: American Society of Anesthesiologists; SVV: Stroke volume variation; CI: Cardiac index; PCIA: Patient-controlled intravenous analgesia; PACU: Post-anesthesia care unit. Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of Huai‘an 82 Hospital (Huai'an, Jiangsu, China. approval number: HA82YY202542) and was registered in the Chinese Clinical Trial Registry (ChiCTR2500106739). All participants gave written informed consent before enrollment. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments. Consent for publication Not applicable. This manuscript does not contain any individual person’s data in any form (e.g., photos, names, or personal identifiers). Availability of data and materials The datasets used and analyzed during the current study are available from the corresponding author upon reasonable request. Competing Interests The authors declare no competing interests. Funding This study was supported by institutional funding from Huai‘an 82 Hospital and its Department of Anesthesiology. The funders had no role in the study design, execution, or manuscript preparation. Authors ’ contributions Dandan Hu and Lin Zong conceived and designed the study. Dandan Hu, Ying Ding, Jie Chen, Ziwei Zhou, Xinzhao Ding, and Mingliang Zhong collected and analyzed the data. Dandan Hu drafted the manuscript. Lin Zong critically revised the manuscript. All authors read and approved the final version. Acknowledgements The authors thank the nursing staff of the Department of Anesthesiology and Department of Orthopedics at Huai’an 82 Hospital for their support during this study. CONSORT statement This randomized controlled trial was conducted and reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) 2025 statement. A completed CONSORT 2025 checklist is provided as Additional file 1. Data availability statement The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request. Analysis code availability The statistical analysis code (SPSS syntax files) is available from the corresponding author upon reasonable request. Patient and public involvement Patients and the public were not involved in the design, conduct, reporting, or dissemination plans of this research. References De Biase G, Akinduro OO, Garcia D, et al. Awake Robotic Minimally Invasive Transforaminal Lumbar Interbody Fusion Under Spinal Anesthesia: A Prospective Study with 1-Year Follow-up. World Neurosurg. 2024;189:e941–7. Matur AV, Palmisciano P, Duah HO, et al. Robotic and navigated pedicle screws are safer and more accurate than fluoroscopic freehand screws: a systematic review and meta-analysis. Spine J. 2023;23(2):197–208. Podder D, Stala O, Hirani R, Karp AM, Etienne M. Comprehensive Approaches to Pain Management in Postoperative Spinal Surgery Patients: Advanced Strategies and Future Directions. Neurol Int. 2025;17(6):94. Chen DJ, Tang L, Chen B, et al. IRF8-Cathepsin S/PAR2 axis-mediated spinal microglia-neuron crosstalk is responsible for the exacerbation of postsurgical pain induced by preoperative stress. Int Immunopharmacol. 2025;161:115034. Chu B, Marwaha K, Sanvictores T, Awosika AO, Ayers D. Physiology, Stress Reaction. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 7, 2024. Acharya K, Rout DK, Kapadia NA et al. Surgical Stress Response: A Physiological Review of the Endocrine, Immune, and Metabolic Changes. Cureus.2025;17(12):e100101. Naftalovich R, Singal A, Iskander AJ. Enhanced Recovery After Surgery (ERAS) protocols for spine surgery - review of literature. Anaesthesiol Intensive Ther. 2022;54(1):71–9. Nasr E, Khalil N, Sarsam M, Omran M, Elhantiry A. An Emerging Paradigm for Safer and Faster Recovery: A Narrative Review on Opioid Sparing Anesthesia in Surgery. Cureus. 2025;17(10):e95726. Mao B, Wang X, Zhang X, Chen M. Opioids With or Without Low-Dose Naloxone During the Perioperative Period: A Systematic Review With Meta-Analysis. Pain Res Manag. 2025;2025:8380502. Gao Y, Ji D, Fang Q, et al. Effect of low-dose norepinephrine combined with goal-directed fluid therapy on postoperative pulmonary complications in lung surgery: A prospective randomized controlled trial. J Clin Anesth. 2024;99:111645. Reysner T, Wieczorowska-Tobis K, Kowalski G, et al. The Influence of Regional Anesthesia on the Systemic Stress Response. Rep (MDPI). 2024;7(4):89. Domagalska M, Ciftsi B, Janusz P, et al. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) levels following erector spinae plane block (ESPB) in posterior lumbar decompression: a randomized, controlled trial. Eur Spine J. 2023;32(12):4192–9. Majage S, Ravikumar RH, Prasanna M, Chandramouli M, Datta PK, Baidya DK. Comparison of efficacy of ultrasound-guided erector spinae plane block versus thoracolumbar interfascial plane block in patients undergoing lumbar spine surgeries: A systematic review and trial sequential meta-analysis. Indian J Anaesth. 2024;68(9):752–61. Chen D, Liu P, Song W, Liu S. Effect of posterior de compression and bone grafting combined with minimally invasive percutaneous pedicle screw fixation on pain and functional recovery in patients with thoracolumbar spinal fractures[J]. Expert Rev Med Devices. 2025;22(5):489–95. Kim MH, Lee KY, Bae SJ, Jo M, Cho JS. Intraoperative dexmedetomidine attenuates stress responses in patients undergoing major spine surgery. Minerva Anestesiol. 2019;85(5):468–77. Zhou Z, Chen Z, Gao L, Sun Q, Tang W. Effect of Minimally Invasive Internal Arch Nailing Surgery on Tissue Traumatic Stress Response in Patients with Vertebral Fractures. Contrast Media Mol Imaging. 2022;2022:2375883. Xu H, Ma L. Advances in Erector Spinae Plane Block for Spinal Surgery. Acta Acad Med Sin. 2024;46(04):560–4. Sharma SK, Sonawane K, Mistry T. A narrative review on fascial plane blocks - Part A: Anatomical foundations and mechanistic insights. Indian J Anaesth. 2026;70(1):127–36. Behem CR, Friedheim T, Holthusen H, et al. Goal-directed colloid versus crystalloid therapy and microcirculatory blood flow following ischemia/reperfusion. Microvasc Res. 2024;152:104630. Acharya K, Rout DK, Kapadia NA, et al. Surgical Stress Response: A Physiological Review of the Endocrine, Immune, and Metabolic Changes. Cureus. 2025;17(12):e100101. Tantri AR, Rahmi R, Marsaban AHM, Satoto D, Rahyussalim AJ, Sukmono RB. Comparison of postoperative IL-6 and IL-10 levels following Erector Spinae Plane Block (ESPB) and classical Thoracolumbar Interfascial Plane (TLIP) block in a posterior lumbar decompression and stabilization procedure: a randomized controlled trial. BMC Anesthesiol. 2023;23(1):13. Wang X, Duan Y, Gao Z, Gu J. Effect of Goal-directed Fluid Therapy on the Shedding of the Glycocalyx Layer in Retroperitoneal Tumour Resection. J Coll Physicians Surg Pak. 2021;31(10):1179–85. Gilbertson LE, Muhly WT, Montana MC, et al. A survey of practice in the anesthetic management of adolescent idiopathic scoliosis spine fusion by the North American Pediatric Spine Anesthesiologists Collaborative. Paediatr Anaesth. 2024;34(7):645–53. Liu H, Xiong L, Xu X, et al. Preparation of Goal-Oriented Nano-Liquid and Its Effect of Paravertebral Nerve Block in Hemodynamics of Patients with Thoracotomy. Sci Adv Mater. 2021;13(10):1960–8. Xu Y, Zhong M, Li S. Opioid-free anesthesia in enhanced recovery after surgery for gastrointestinal surgery: current status, challenges, and prospects. Front Pharmacol. 2025;16:1662818. Bakare AA, Varela JR, Ahn YJ, et al. Erector spinae plane block during standalone anterior lumbar surgery: impact on early ambulation, length of stay, and inpatient opioid use. J Neurosurg Spine. 2025;44(1):90–8. Naftalovich R, Singal A, Iskander AJ. Enhanced Recovery After Surgery (ERAS) protocols for spine surgery – review of literature. Anaesthesiol Intensive Ther. 2022;54(1):71–9. Che L, Yu JW, Zhang YL, et al. Intraoperative Blood Pressure Lability Acts as a Key Mediator in the Impacts of Goal-Directed Fluid Therapy on Postoperative Complications in Patients Undergoing Major Spine Surgery. Chin Med Sci J. 2023;38(4):257–64. Sun Y, Liang X, Chai F, Shi D, Wang Y. Goal-directed fluid therapy using stroke volume variation on length of stay and postoperative gastrointestinal function after major abdominal surgery-a randomized controlled trial. BMC Anesthesiol. 2023;23(1):397. Additional Declarations No competing interests reported. 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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-9245316","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":634507916,"identity":"421c9e8e-ad13-46bb-88f0-44252a4c7f4a","order_by":0,"name":"Dandan Hu¹","email":"","orcid":"","institution":"Huai’an 82 Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dandan","middleName":"","lastName":"Hu¹","suffix":""},{"id":634507917,"identity":"d1a7ddce-cbc9-4071-949d-c8ae4fdf8a87","order_by":1,"name":"Ying Ding","email":"","orcid":"","institution":"Huai’an 82 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Hospital, Affiliated Hospital of Medical School,Nanjing University","correspondingAuthor":true,"prefix":"","firstName":"Lin","middleName":"","lastName":"Zong²","suffix":""}],"badges":[],"createdAt":"2026-03-27 13:39:26","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9245316/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9245316/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":108941617,"identity":"d951e5ce-f6ce-4f56-a21f-d545d7217426","added_by":"auto","created_at":"2026-05-11 05:36:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":170499,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eCONSORT 2025 flow diagram\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"CONSORT2025GDFTESPB1.png","url":"https://assets-eu.researchsquare.com/files/rs-9245316/v1/d7dcaef308a5de092b193f3b.png"},{"id":108978193,"identity":"01a1ce2b-effd-4b89-87a6-4dbd34f529d2","added_by":"auto","created_at":"2026-05-11 11:34:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":553723,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9245316/v1/8d807b2f-4b18-4c96-87ce-d6ea29faf812.pdf"},{"id":108941619,"identity":"6fad64f7-da9b-4e9e-aeb9-14a55ec62ad0","added_by":"auto","created_at":"2026-05-11 05:36:58","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":32018,"visible":true,"origin":"","legend":"","description":"","filename":"CONSORT2025editablechecklist.docx","url":"https://assets-eu.researchsquare.com/files/rs-9245316/v1/0d192d5459d6d64edacc3888.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Optimizing Perioperative Outcomes in Robot-Assisted Spine Surgery: Combined Goal-Directed Fluid Therapy and Erector Spinae Plane Block Modulates Stress and Inflammation:A Randomized Controlled Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eRobot-assisted spine surgery has emerged as a hallmark of precision medicine, with pedicle screw placement accuracy exceeding 95% and reduced intraoperative fluoroscopy and neurovascular injury compared with conventional techniques\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. However, despite these minimally invasive advantages, inherent surgical trauma, prolonged anesthesia, and unique patient positioning still provoke the hypothalamic\u0026ndash;pituitary\u0026ndash;adrenal (HPA) axis and sympathetic\u0026ndash;adrenal\u0026ndash;medullary (SAM) system, eliciting a profound surgical stress response characterized by neuroendocrine activation and amplified inflammatory cascades\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. This response manifests as elevated serum cortisol (Cor), norepinephrine (NE), and glucose (GLU)\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e, which not only directly suppress immune function but also correlate with postoperative infections, insulin resistance, coagulopathy, and chronic pain, ultimately delaying recovery and increasing complications\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eManaging the stress response remains a key objective in anesthetic care for spine surgery. While general anesthesia effectively induces unconsciousness, it inadequately prevents nociceptive signals from reaching the central nervous system, leaving the \"peripheral nociceptive stimulus\u0026ndash;central sensitization\" pathway intact\u003csup\u003e[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. Moreover, inappropriate fluid management can exacerbate hemodynamic fluctuations and amplify inflammation through ischemia\u0026ndash;reperfusion injury\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e. Although deep anesthesia or high-dose opioids may offer some advantages, they elevate the likelihood of postoperative nausea and vomiting (PONV), hypotension, and respiratory depression, conflicting with enhanced recovery after surgery (ERAS) principles\u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eGoal-directed fluid therapy (GDFT) employs dynamic hemodynamic variables, including stroke volume variation (SVV) and cardiac index (CI), to guide individualized fluid administration, achieving a precise balance between maintaining tissue perfusion and avoiding volume overload\u003csup\u003e[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. On the other hand, regional block techniques, as integral components of multimodal analgesia, directly suppress stress axis activation by blocking nociceptive input\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. The erector spinae plane block (ESPB), owing to its ease of performance and extensive coverage of the paravertebral space, has been increasingly used in posterior spine surgery with favorable outcomes\u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eAlthough GDFT and ESPB have each demonstrated value in stress modulation, their synergistic effects in robot-assisted pedicle screw fixation remain unexplored. Particularly in the context of robotic surgery, the potential of optimized anesthetic strategies to further enhance the benefits of minimally invasive techniques is a key scientific question in the evolution of ERAS pathways. This study aimed to prospectively assess the effects of integrating GDFT and ESPB on perioperative stress response and ERAS outcomes in patients undergoing robot-assisted pedicle screw fixation.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design and participants\u003c/h2\u003e \u003cp\u003eThis prospective, single-center, randomized controlled trial was carried out at Huai\u0026rsquo;an 82 Hospital from January to October 2025. The study protocol was approved by the hospital\u0026rsquo;s Ethics Committee (approval number: HA82YY202542) and was registered in the Chinese Clinical Trial Registry (ChiCTR2500106739). All participants provided written informed consent before enrollment.\u003c/p\u003e \u003cp\u003eEligible participants were individuals aged 18 to 75 years, classified as American Society of Anesthesiologists (ASA) physical status I\u0026ndash;III, and scheduled for elective robot-assisted posterior lumbar pedicle screw fixation. Exclusion criteria encompassed: (1) severe cardiac, pulmonary, hepatic (Child\u0026ndash;Pugh class C), or renal impairment (eGFR\u0026thinsp;\u0026lt;\u0026thinsp;30 mL/min/1.73 m\u0026sup2;); (2) coagulation disorders (INR\u0026thinsp;\u0026gt;\u0026thinsp;1.5 or platelet count\u0026thinsp;\u0026lt;\u0026thinsp;80\u0026times;10⁹/L); (3) local infection at the puncture site or spinal deformity; (4) allergy to ropivacaine; (5) long-term use of glucocorticoids or immunosuppressants.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eRandomization and blinding\u003c/h3\u003e\n\u003cp\u003eUsing SAS 9.4 software, 80 patients were evenly randomized to either the control group (general anesthesia\u0026thinsp;+\u0026thinsp;conventional fluid management) or the intervention group (general anesthesia\u0026thinsp;+\u0026thinsp;GDFT\u0026thinsp;+\u0026thinsp;ESPB). Simple randomization with a 1:1 allocation ratio was performed. The allocation sequence was generated by a statistician not involved in patient recruitment or outcome assessment. Patient enrollment was performed by the attending surgeons, and group assignment was carried out by a research nurse who opened the sequentially numbered, opaque, sealed envelopes just before anesthesia induction. Allocation was concealed in sequentially numbered, opaque sealed envelopes opened just before induction. Given the nature of the interventions (ESPB and GDFT), blinding of the attending anesthesiologist was not feasible. However, outcome assessors and data analysts remained blinded to group assignments.For analysis, groups were coded as \u0026ldquo;A\u0026rdquo; and \u0026ldquo;B\u0026rdquo; until the final statistical analysis was completed.\u003c/p\u003e\n\u003ch3\u003eAnesthetic management\u003c/h3\u003e\n\u003cp\u003ePreoperative fasting was observed for all patients, with a duration of 8 hours for food and 2 hours for clear liquids. Following their arrival in the operating theatre, patients were connected to standard monitors (comprising electrocardiography, non-invasive blood pressure, and pulse oximetry). Subsequently, under local anesthesia, a catheter was placed in the radial artery to facilitate continuous hemodynamic monitoring.\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eGeneral anesthesia protocol (both groups)\u003c/strong\u003e \u003cp\u003eThe anesthetic protocol commenced with an intravenous induction dose of midazolam (0.2 mg/kg), sufentanil (0.5 \u0026micro;g/kg), etomidate (0.3 mg/kg), and cisatracurium (0.15 mg/kg). Upon successful tracheal intubation, mechanical ventilation was commenced using a tidal volume of 6\u0026ndash;8 mL/kg, with the respiratory frequency titrated to achieve an end-tidal CO₂ tension of 35\u0026ndash;45 mmHg. Subsequently, anesthesia was sustained by continuous infusions of propofol (4\u0026ndash;6 mg/kg/h), remifentanil (0.1\u0026ndash;0.3 \u0026micro;g/kg/min), and cisatracurium (0.1 mg/kg/h). The infusion rates were adjusted to maintain a target bispectral index (BIS) range of 40 to 60.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eIntervention group \u0026ndash; ESPB\u003c/strong\u003e \u003cp\u003eThirty minutes before surgical incision, under ultrasound guidance (Sonosite X-Porte, Fujifilm, USA), the erector spinae plane block was performed bilaterally at the level corresponding to the surgical vertebral level. With the patient in position, a linear array transducer (6\u0026ndash;13 MHz) was oriented longitudinally 3 cm lateral to the spinous process to reveal the transverse process and its overlying erector spinae muscle. An 80-mm, 22-gauge needle was then inserted in-plane, targeting the transverse process until bony contact was achieved. After negative aspiration, bilateral injections of 20 mL 0.375% ropivacaine were performed, and the injectate was seen tracking beneath the erector spinae muscle. Twenty minutes after injection, the sensory block level was assessed using an ice swab; surgery proceeded only when the block covered the planned incision area.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eIntervention group \u0026ndash; GDFT\u003c/b\u003e: The radial artery catheter was connected to the FloTrac system (Edwards Lifesciences, Irvine, CA, USA) to enable continuous monitoring of SVV and CI. Fluid management was guided to maintain SVV\u0026thinsp;\u0026le;\u0026thinsp;13% and CI\u0026thinsp;\u0026ge;\u0026thinsp;2.5 L/min/m\u0026sup2;. A combination of crystalloid (Ringer\u0026rsquo;s bicarbonate solution) and colloid (succinylated gelatin) was infussed at a 2:1 ratio. Urine output remained at or above 0.5 mL/kg/h.\u003c/p\u003e \u003cp\u003e \u003cb\u003eControl group\u003c/b\u003e: Patients received the same general anesthesia but with conventional fluid management: crystalloid and colloid were infused empirically at 10 mL/kg/h in a 2:1 ratio.\u003c/p\u003e\n\u003ch3\u003ePostoperative analgesia\u003c/h3\u003e\n\u003cp\u003eThe postoperative analgesia protocol for all patients was standardized to patient-controlled intravenous analgesia (PCIA). The analgesic solution comprised sufentanil (1.5 \u0026micro;g/kg) and tropisetron (10 mg), diluted with normal saline to a total volume of 100 mL. The PCIA device was programmed with a continuous background infusion of 2 mL/h, a patient-controlled bolus of 1 mL, and a 20-minute lockout interval. In the post-anesthesia care unit (PACU), intravenous rescue analgesia with sufentanil (2.5 \u0026micro;g) was provided when the visual analog scale (VAS) score exceeded 3, and this dose could be repeated if required.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003e \u003cb\u003ePrimary outcomes\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eSerum cortisol (Cor) and norepinephrine (NE) concentrations, along with blood glucose (GLU), were assessed at four time intervals: preoperatively (T₀), during screw placement (T₁), at surgery end (T₂), and 24 hours post-surgery (T₄). Blood samples (5 mL) were subjected to centrifugation at 3000 rpm for 10 minutes, and the resulting serum was preserved at \u0026minus;\u0026thinsp;80\u0026deg;C until subsequent analysis. Cor was measured by electrochemiluminescence immunoassay (Cobas e601, Roche Diagnostics, Switzerland); NE was measured using enzyme-linked immunosorbent assay (ELISA) with commercial kits (IBL International, Hamburg, Germany); GLU was determined by the glucose oxidase method.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003eIL-6, IL-10, and TNF-α levels were evaluated at identical time points using ELISA kits (R\u0026amp;D Systems, Minneapolis, MN, USA) following manufacturer guidelines. The coefficients of variation for intra-assay and inter-assay precision were less than 10% and 15%, respectively, based on the analysis of all samples in duplicate.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e \u003cp\u003e \u003cb\u003eSecondary outcomes\u003c/b\u003e:\u003c/p\u003e \u003cp\u003e \u003col\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eHeart rate (HR) and mean arterial pressure (MAP) were documented at T₀, T₁, T₂, and T₄. MAP fluctuation amplitude was calculated as ΔMAP = (measured \u0026ndash; baseline)/baseline \u0026times; 100%.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTotal crystalloid and colloid volumes, and total remifentanil dose were recorded.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eResting VAS scores (0\u0026ndash;10 cm scale) were assessed at T₀ (preoperative baseline), 30 min after extubation (T₃), T₄, and 48 h postoperatively (T₅). Number of rescue analgesia episodes in the PACU was recorded.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eTime to first ambulation (hours from end of surgery to independent walking with assistance) and length of postoperative hospital stay (days).\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003cspan\u003e \u003cli\u003e \u003cp\u003eComplications: Postoperative agitation (defined as a Riker Sedation-Agitation Scale score\u0026thinsp;\u0026ge;\u0026thinsp;5), PONV (presence of nausea or vomiting within 48 h), and respiratory depression (characterized by a respiratory rate below 8 breaths/min or SpO₂ \u0026lt;90% while breathing room air) were recorded.\u003c/p\u003e \u003c/li\u003e \u003c/span\u003e \u003c/ol\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSample size calculation\u003c/h2\u003e \u003cp\u003eSample size was based on the primary outcome of serum cortisol at T₁. From a pilot study of 10 patients per group, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD cortisol at T₁ was 284.7\u0026thinsp;\u0026plusmn;\u0026thinsp;35.1 ng/mL in the control group and 245.3\u0026thinsp;\u0026plusmn;\u0026thinsp;30.2 ng/mL in the intervention group. To detect a 15% difference with a two-sided α of 0.05 and power of 80%, 36 patients per group were required. The sample size was set at 40 patients per group, which includes an adjustment for a projected 10% attrition rate.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were carried out using SPSS (version 26.0, IBM Corp., Armonk, NY, USA) and GraphPad Prism (version 9.0, GraphPad Software, San Diego, CA, USA). The normality of data distribution was examined by the Shapiro\u0026ndash;Wilk test. All analyses were performed according to the intention-to-treat principle, including all randomized patients in the groups to which they were originally assigned. Continuous variables with a normal distribution were summarized as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) and compared using either the independent t-test or repeated-measures analysis of variance (ANOVA) followed by Bonferroni post‑hoc correction. Non‑normally distributed data were presented as median (interquartile range) and analyzed with the Mann\u0026ndash;Whitney U test. Categorical variables were expressed as frequencies (percentages) and compared using the chi‑square test or Fisher\u0026rsquo;s exact test, as appropriate. For the repeated measurements (HR, MAP, Cor, NE, GLU, IL‑6, TNF‑α, IL‑10), a two‑way repeated‑measures ANOVA was performed to evaluate the effects of group, time, and their interaction.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eChanges after trial registration\u003c/h3\u003e\n\u003cp\u003eNo changes were made to the trial methods or outcomes after registration at the Chinese Clinical Trial Registry (ChiCTR2500106739).\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePatient characteristics\u003c/h2\u003e \u003cp\u003eA total of 80 enrolled patients were randomly assigned to two groups (n\u0026thinsp;=\u0026thinsp;40 per group). All patients completed the study without protocol violations. The participant flow diagram is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The two groups were well-balanced regarding baseline demographics and clinical characteristics (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 patient characteristics\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=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntervention group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\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\u003e56.42\u0026thinsp;\u0026plusmn;\u0026thinsp;8.25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55.37\u0026thinsp;\u0026plusmn;\u0026thinsp;8.78\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.975\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex (male/female)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19/21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20/20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.632\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u0026sup2;)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.721\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA status (I/II/III)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12/23/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14/21/5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.842\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (17.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (20.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.550\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (7.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.690\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical levels (L2\u0026ndash;L5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.834\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\u003e128\u0026thinsp;\u0026plusmn;\u0026thinsp;25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e131\u0026thinsp;\u0026plusmn;\u0026thinsp;28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.612\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\u003eData are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD or n (%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePerioperative hemodynamics\u003c/h2\u003e \u003cp\u003eAt baseline (T₀), HR and MAP were similar between groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). In the control group, HR significantly increased from baseline at T₁, T₂ (both \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), whereas the intervention group maintained stable HR. At T₁, HR increase from baseline was 4.6% in the intervention group vs. 21.4% in controls (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). MAP also increased significantly in controls at T₁ (+\u0026thinsp;19.0% vs. baseline) but only minimally in the intervention group (+\u0026thinsp;4.5%). Using two-way repeated-measures ANOVA, significant group \u0026times; time interactions were observed for both HR (\u003cem\u003eF\u003c/em\u003e\u0026thinsp;=\u0026thinsp;28.73, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and MAP (\u003cem\u003eF\u003c/em\u003e\u0026thinsp;=\u0026thinsp;25.16, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\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\u003ePerioperative hemodynamic changes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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=\"\u0026plusmn;\" 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=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT₀\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT₁\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT₂\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eT₄\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e (interaction)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eHR (bpm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e76.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e92.5\u0026thinsp;\u0026plusmn;\u0026thinsp;11.3\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e88.7\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e82.4\u0026thinsp;\u0026plusmn;\u0026thinsp;7.8\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e75.8\u0026thinsp;\u0026plusmn;\u0026thinsp;7.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e79.3\u0026thinsp;\u0026plusmn;\u0026thinsp;8.5\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.2\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e77.5\u0026thinsp;\u0026plusmn;\u0026thinsp;6.9\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMAP (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e85.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e101.6\u0026thinsp;\u0026plusmn;\u0026thinsp;9.8\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e94.2\u0026thinsp;\u0026plusmn;\u0026thinsp;8.3\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e89.1\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e84.9\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e88.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e86.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.8\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e85.3\u0026thinsp;\u0026plusmn;\u0026thinsp;6.0\u003csup\u003eab\u003c/sup\u003e\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\u003eData are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. A two-way repeated-measures ANOVA was used to assess the effects of group, time, and their interaction. A P-interaction value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicates a significant interaction effect between group and time. aP\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. T₀ within group; bP\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. control at same time point(Bonferroni post-hoc correction).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eStress hormones\u003c/h2\u003e \u003cp\u003eAt T₀, Cor, NE, and GLU were similar between groups. In the control group, Cor increased more than twofold at T₁, whereas the increase in the intervention group was markedly blunted: Cor at T₁ was 33.5% lower than in controls ( \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). NE and GLU followed similar patterns, with reductions of 40.0% and 30.3%, respectively, at T₁ (both \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The beneficial effects persisted through T₄ for all markers (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\u003ePerioperative stress hormones\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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=\"\u0026plusmn;\" 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=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT₀\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT₁\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT₂\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eT₄\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e (interaction)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eCortisol (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e125.6\u0026thinsp;\u0026plusmn;\u0026thinsp;20.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e284.7\u0026thinsp;\u0026plusmn;\u0026thinsp;35.1\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e198.5\u0026thinsp;\u0026plusmn;\u0026thinsp;28.9\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e168.3\u0026thinsp;\u0026plusmn;\u0026thinsp;25.4\u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e124.8\u0026thinsp;\u0026plusmn;\u0026thinsp;19.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e189.2\u0026thinsp;\u0026plusmn;\u0026thinsp;26.5\u003csup\u003ead\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e152.7\u0026thinsp;\u0026plusmn;\u0026thinsp;22.1\u003csup\u003eabd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e136.4\u0026thinsp;\u0026plusmn;\u0026thinsp;20.8\u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eNE (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e235.4\u0026thinsp;\u0026plusmn;\u0026thinsp;42.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e587.6\u0026thinsp;\u0026plusmn;\u0026thinsp;68.9\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e402.3\u0026thinsp;\u0026plusmn;\u0026thinsp;55.7\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e315.8\u0026thinsp;\u0026plusmn;\u0026thinsp;47.2\u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e233.9\u0026thinsp;\u0026plusmn;\u0026thinsp;40.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e352.4\u0026thinsp;\u0026plusmn;\u0026thinsp;51.3\u003csup\u003ead\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e286.1\u0026thinsp;\u0026plusmn;\u0026thinsp;43.6\u003csup\u003eabd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e254.7\u0026thinsp;\u0026plusmn;\u0026thinsp;38.4\u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eGLU (mmol/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003csup\u003ead\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003csup\u003eabd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003csup\u003eabcd\u003c/sup\u003e\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\u003eData are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. aP\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. T₀ within group; bP\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. T₁ within group; cP\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. T₂ within group; dP\u0026thinsp;\u0026lt;\u0026thinsp;0.05 vs. control at same time point (Bonferroni post-hoc correction).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eInflammatory cytokines\u003c/h2\u003e \u003cp\u003eIn the control group, IL-6 and TNF-α peaked at T₂ and remained elevated at T₄. In contrast, the intervention group exhibited significantly lower IL-6 and TNF-α at T₂ and T₄ (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). IL-10 levels were higher in the intervention group at T₂ and T₄ (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), indicating enhanced anti-inflammatory compensation. The IL-6/IL-10 ratio, a marker of pro-/anti-inflammatory imbalance, was significantly lower in the intervention group at T₂ and T₄ (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (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\u003ePerioperative inflammatory cytokines\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\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=\"\u0026plusmn;\" 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=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGroup\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eT₀\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eT₁\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eT₂\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eT₄\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e (interaction)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIL-6 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45.6\u0026thinsp;\u0026plusmn;\u0026thinsp;8.9\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e32.4\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e4.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18.2\u0026thinsp;\u0026plusmn;\u0026thinsp;4.1\u003csup\u003ead\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e26.3\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003csup\u003eabd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e18.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eTNF-α (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.6\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.8\u0026thinsp;\u0026plusmn;\u0026thinsp;4.5\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e16.5\u0026thinsp;\u0026plusmn;\u0026thinsp;3.8\u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.6\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4\u003csup\u003ead\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.2\u0026thinsp;\u0026plusmn;\u0026thinsp;3.1\u003csup\u003eabd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.8\u0026thinsp;\u0026plusmn;\u0026thinsp;2.5\u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIL-10 (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.2\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003csup\u003ead\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003csup\u003eabd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003csup\u003eabcd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eIL-6/IL-10 ratio\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.9\u0026thinsp;\u0026plusmn;\u0026thinsp;1.3\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.8\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.7\u0026thinsp;\u0026plusmn;\u0026thinsp;1.6\u003csup\u003eabc\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eIntervention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.6\u0026thinsp;\u0026plusmn;\u0026thinsp;0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003csup\u003ead\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003csup\u003eabd\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003csup\u003eabcd\u003c/sup\u003e\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\u003eData are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD. \u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 vs. T₀ within group; \u003csup\u003eb\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 vs. T₁ within group; \u003csup\u003ec\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 vs. T₂ within group; \u003csup\u003ed\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05 vs. control at same time point.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eIntraoperative fluid and opioid consumption\u003c/h2\u003e \u003cp\u003eThe intervention group received significantly less crystalloid (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and colloid (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) compared with controls. Remifentanil consumption was reduced by 32.1% in the intervention group ( \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eIntraoperative fluid and opioid consumption\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntervention group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCrystalloid (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2180\u0026thinsp;\u0026plusmn;\u0026thinsp;320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1650\u0026thinsp;\u0026plusmn;\u0026thinsp;290\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColloid (mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e980\u0026thinsp;\u0026plusmn;\u0026thinsp;150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e750\u0026thinsp;\u0026plusmn;\u0026thinsp;130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemifentanil (mg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u003eData are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.Comparisons between groups were performed using the independent t-test. A \u003cem\u003eP\u003c/em\u003e-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003ePostoperative pain and recovery\u003c/h2\u003e \u003cp\u003ePostoperative VAS scores were significantly lower in the intervention group at T₃ (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), T₄ (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and T₅ (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Rescue analgesia episodes were reduced by 65.6% in the intervention group ( \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab6\" class=\"InternalRef\"\u003e6\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab6\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePostoperative pain and rescue analgesia\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntervention group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVAS at T₃\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e4.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVAS at T₄\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.9\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVAS at T₅\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRescue analgesia (episodes)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u003eData are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.VAS scores were compared between groups using the independent t-test; the number of rescue analgesia episodes was compared using the Mann-Whitney U test.\u003c/p\u003e \u003cp\u003eTime to first ambulation was significantly shorter in the intervention group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), as was postoperative hospital stay (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Total hospitalization costs were also reduced ( \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) (Table\u0026nbsp;\u003cspan refid=\"Tab7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab7\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePostoperative recovery and costs\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParameter\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntervention group\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to first ambulation (h)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e24.5\u0026thinsp;\u0026plusmn;\u0026thinsp;4.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e16.8\u0026thinsp;\u0026plusmn;\u0026thinsp;3.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative hospital stay (days)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;1.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.2\u0026thinsp;\u0026plusmn;\u0026thinsp;1.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal hospitalization cost (thousand USD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e5.8\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e5.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\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\u003eData are mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD.All data were confirmed to follow a normal distribution by the Shapiro-Wilk test, and comparisons between groups were performed using the independent t-test.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003eComplications\u003c/h2\u003e \u003cp\u003eThe incidence of PONV was lower in the intervention group (7.5% vs. 15.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.042), as was postoperative agitation (2.5% vs. 12.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.045). Total complication rate was significantly reduced (10.0% vs. 32.5%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012). No significant difference was observed in respiratory depression (2.5% vs. 5.0%, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.151) (Table\u0026nbsp;\u003cspan refid=\"Tab8\" class=\"InternalRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab8\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 8\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003ePostoperative complications\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=\"char\" char=\".\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eComplication\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eIntervention group (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePONV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (15.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (7.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAgitation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory depression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (5.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (32.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (10.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.012\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\u003eData are n (%). Comparisons between groups were performed using the chi-square test, or Fisher's exact test when any expected frequency was \u0026lt;\u0026thinsp;5.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrates that the combination of GDFT and ESPB in robot-assisted pedicle screw fixation surgery significantly reduces perioperative stress responses at both neuroendocrine and inflammatory levels. The intervention group exhibited marked reductions in stress hormones (Cor, NE, GLU), pro-inflammatory cytokines (IL-6, TNF-α), and a more balanced anti-inflammatory response (higher IL-10), accompanied by improved hemodynamic stability, reduced opioid consumption, superior postoperative analgesia, accelerated recovery, and fewer complications. These findings extend our understanding of stress modulation in robotic spine surgery and provide a mechanistic rationale for integrating precision anesthesia into ERAS pathways.\u003c/p\u003e \u003cp\u003eDespite the minimally invasive nature of robotic surgery, our results confirm that the moment of pedicle screw placement (T₁) still elicits a pronounced stress response, comparable in magnitude to that associated with open surgery in previous studies\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. This observation challenges the assumption that robotic techniques alone reduce stress and underscores the need for targeted anesthetic interventions. ESPB, by blocking nociceptive input from the surgical field, directly inhibits HPA and SAM activation\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e. The 33.5% reduction in cortisol and 40.0% reduction in NE at T₁ in our intervention group align with previous reports of regional anesthesia attenuating the surgical stress response\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. However, the addition of GDFT may provide synergistic benefit by optimizing tissue perfusion and minimizing ischemia\u0026ndash;reperfusion injury, which can independently activate the HPA axis through hypoxia-induced release of corticotropin-releasing hormone\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eA key novelty of our study is the comprehensive assessment of the inflammatory cascade. The intervention group demonstrated significantly lower IL-6 and TNF-α, coupled with higher IL-10, indicating a shift toward a more regulated inflammatory state. The IL-6/IL-10 ratio, a sensitive marker of pro-/anti-inflammatory imbalance, was markedly reduced at T₂ and T₄. This is clinically important because excessive inflammation after surgery is associated with prolonged pain, impaired wound healing, and infectious complications\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e. The anti-inflammatory effect likely stems from two complementary mechanisms: first, ESPB reduces the release of pro-inflammatory mediators by blocking neural signals that trigger inflammatory gene expression\u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e; second, GDFT-guided fluid administration prevents both hypovolemia-induced tissue hypoperfusion and hypervolemia-induced endothelial glycocalyx shedding, both of which can activate damage-associated molecular patterns (DAMPs) and amplify inflammation\u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Our findings extend those of Gilbertson et al.\u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/sup\u003e, who demonstrated that regional anesthesia combined with individualized fluid therapy reduces inflammatory markers in adolescent idiopathic scoliosis surgery.\u003c/p\u003e \u003cp\u003eThe intervention group exhibited remarkable hemodynamic stability during the most stimulating surgical phase (T₁). This likely reflects the dual effect of ESPB and GDFT. Traditional fluid management often leads to either hypotension (if under-resuscitated) or hypertension (if volume overloaded) in response to surgical stress, both of which can be deleterious. Our results are consistent with Liu et al.\u003csup\u003e[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e, who found that paravertebral block plus GDFT reduced hemodynamic fluctuations in thoracotomy patients. The 32.1% reduction in remifentanil consumption is a direct consequence of ESPB providing effective surgical analgesia, which aligns with the known opioid-sparing effect of regional anesthesia\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e.Reducing opioid exposure not only decreases side effects such as PONV but also preserves gastrointestinal motility and facilitates early mobilization\u003csup\u003e[\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eEarly ambulation is a cornerstone of enhanced recovery after surgery (ERAS), reducing the risk of thromboembolic events and accelerating functional recovery. Conventional anesthesia regimens, often limited by suboptimal analgesia and opioid-related side effects, tend to delay the first ambulation of patients undergoing lumbar spine surgery to more than 24 hours postoperatively\u003csup\u003e[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/sup\u003e. In this study, the time to first ambulation in the intervention group was advanced to 16.8 hours, representing a 31.4% reduction compared with the control group. This marked improvement was attributable to effective pain control (resting VAS\u0026thinsp;\u0026lt;\u0026thinsp;2) and a low incidence of adverse effects.. The 12.1% reduction in hospitalization costs further underscores the economic benefits of this combined strategy, in agreement with Che et al.\u003csup\u003e[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/sup\u003e and Oh et al.\u003csup\u003e[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e, who reported that GDFT and ESPB individually improve outcomes in major spine surgery.\u003c/p\u003e \u003cp\u003eThe intervention significantly reduced overall complication rates, particularly PONV and postoperative agitation. The lower incidence of PONV can be attributed to both the opioid-sparing effect and the improvement in splanchnic perfusion associated with GDFT, which effectively reduces the risk of intestinal edema and gastrointestinal congestion, thereby accelerating the recovery of postoperative gastrointestinal function\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/sup\u003e. Importantly, respiratory depression was not increased, confirming the safety profile of this multimodal approach under standard monitoring.\u003c/p\u003e \u003cp\u003eIt is important to acknowledge several methodological limitations. The first concerns the single-center setting and the relatively small sample size, a factor that inherently constrains the generalizability of the conclusions. Second, while we measured key inflammatory cytokines, we did not assess upstream regulators such as high-mobility group box 1 (HMGB1) or downstream transcription factors (e.g., NF-κB), which would provide deeper mechanistic insight. Third, long-term outcomes such as chronic pain incidence and functional disability (e.g., Oswestry Disability Index) were not evaluated. Fourth, the optimal concentrations of ropivacaine for ESPB and the ideal GDFT parameters in this setting remain to be determined.\u003c/p\u003e \u003cp\u003eFuture multicenter trials with larger cohorts are warranted to confirm our findings. Additionally, mechanistic studies exploring the effects of GDFT+ESPB on DAMP release, endothelial glycocalyx integrity, and immune cell function would further elucidate the pathways involved. Finally, cost-effectiveness analyses incorporating long-term outcomes would strengthen the case for widespread adoption of this combined strategy.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn robot-assisted pedicle screw fixation, the combination of GDFT and ESPB effectively suppresses perioperative stress response through dual modulation of neuroendocrine activation and inflammatory cascades. This approach reduces opioid consumption, optimizes postoperative analgesia, accelerates functional recovery, and lowers complication rates, all while maintaining safety. Our findings highlight that even with robotic precision, anesthetic strategies must actively address the surgical stress response to fully realize the benefits of minimally invasive techniques. Integrating GDFT and ESPB into ERAS protocols represents a promising advancement in precision perioperative care for spine surgery.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eGDFT: Goal-directed fluid therapy; ESPB: Erector spinae plane block; Cor: Cortisol; NE: Norepinephrine; GLU: Glucose; IL-6: Interleukin-6; TNF-\u0026alpha;: Tumor necrosis factor-\u0026alpha;; IL-10: Interleukin-10; HR: Heart rate; MAP: Mean arterial pressure; VAS: Visual analogue scale; ERAS: Enhanced recovery after surgery; PONV: Postoperative nausea and vomiting; ASA: American Society of Anesthesiologists; SVV: Stroke volume variation; CI: Cardiac index; PCIA: Patient-controlled intravenous analgesia; PACU: Post-anesthesia care unit.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of Huai\u0026lsquo;an 82 Hospital (Huai\u0026apos;an, Jiangsu, China. approval number: HA82YY202542) and was registered in the Chinese Clinical Trial Registry (ChiCTR2500106739). All participants gave written informed consent before enrollment. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. This manuscript does not contain any individual person\u0026rsquo;s data in any form (e.g., photos, names, or personal identifiers).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by institutional funding from Huai\u0026lsquo;an 82 Hospital and its Department of Anesthesiology. The funders had no role in the study design, execution, or manuscript preparation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u003c/strong\u003e\u003cstrong\u003e\u0026rsquo;\u003c/strong\u003e\u003cstrong\u003e\u0026nbsp;contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDandan Hu and Lin Zong conceived and designed the study. Dandan Hu, Ying Ding, Jie Chen, Ziwei Zhou, Xinzhao Ding, and Mingliang Zhong collected and analyzed the data. Dandan Hu drafted the manuscript. Lin Zong critically revised the manuscript. All authors read and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors thank the nursing staff of the Department of Anesthesiology and Department of Orthopedics at Huai\u0026rsquo;an 82 Hospital for their support during this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSORT statement\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis randomized controlled trial was conducted and reported in accordance with the CONSORT (Consolidated Standards of Reporting Trials) 2025 statement. A completed CONSORT 2025 checklist is provided as Additional file 1.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAnalysis code availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe statistical analysis code (SPSS syntax files) is available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePatient and public involvement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePatients and the public were not involved in the design, conduct, reporting, or dissemination plans of this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDe Biase G, Akinduro OO, Garcia D, et al. Awake Robotic Minimally Invasive Transforaminal Lumbar Interbody Fusion Under Spinal Anesthesia: A Prospective Study with 1-Year Follow-up. World Neurosurg. 2024;189:e941\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMatur AV, Palmisciano P, Duah HO, et al. Robotic and navigated pedicle screws are safer and more accurate than fluoroscopic freehand screws: a systematic review and meta-analysis. Spine J. 2023;23(2):197\u0026ndash;208.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePodder D, Stala O, Hirani R, Karp AM, Etienne M. Comprehensive Approaches to Pain Management in Postoperative Spinal Surgery Patients: Advanced Strategies and Future Directions. Neurol Int. 2025;17(6):94.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen DJ, Tang L, Chen B, et al. IRF8-Cathepsin S/PAR2 axis-mediated spinal microglia-neuron crosstalk is responsible for the exacerbation of postsurgical pain induced by preoperative stress. Int Immunopharmacol. 2025;161:115034.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChu B, Marwaha K, Sanvictores T, Awosika AO, Ayers D. Physiology, Stress Reaction. In: StatPearls. Treasure Island (FL): StatPearls Publishing; May 7, 2024.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAcharya K, Rout DK, Kapadia NA et al. Surgical Stress Response: A Physiological Review of the Endocrine, Immune, and Metabolic Changes. Cureus.2025;17(12):e100101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaftalovich R, Singal A, Iskander AJ. Enhanced Recovery After Surgery (ERAS) protocols for spine surgery - review of literature. Anaesthesiol Intensive Ther. 2022;54(1):71\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNasr E, Khalil N, Sarsam M, Omran M, Elhantiry A. An Emerging Paradigm for Safer and Faster Recovery: A Narrative Review on Opioid Sparing Anesthesia in Surgery. Cureus. 2025;17(10):e95726.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMao B, Wang X, Zhang X, Chen M. Opioids With or Without Low-Dose Naloxone During the Perioperative Period: A Systematic Review With Meta-Analysis. Pain Res Manag. 2025;2025:8380502.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao Y, Ji D, Fang Q, et al. Effect of low-dose norepinephrine combined with goal-directed fluid therapy on postoperative pulmonary complications in lung surgery: A prospective randomized controlled trial. J Clin Anesth. 2024;99:111645.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReysner T, Wieczorowska-Tobis K, Kowalski G, et al. The Influence of Regional Anesthesia on the Systemic Stress Response. Rep (MDPI). 2024;7(4):89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDomagalska M, Ciftsi B, Janusz P, et al. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) levels following erector spinae plane block (ESPB) in posterior lumbar decompression: a randomized, controlled trial. Eur Spine J. 2023;32(12):4192\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMajage S, Ravikumar RH, Prasanna M, Chandramouli M, Datta PK, Baidya DK. Comparison of efficacy of ultrasound-guided erector spinae plane block versus thoracolumbar interfascial plane block in patients undergoing lumbar spine surgeries: A systematic review and trial sequential meta-analysis. Indian J Anaesth. 2024;68(9):752\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen D, Liu P, Song W, Liu S. Effect of posterior de compression and bone grafting combined with minimally invasive percutaneous pedicle screw fixation on pain and functional recovery in patients with thoracolumbar spinal fractures[J]. Expert Rev Med Devices. 2025;22(5):489\u0026ndash;95.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim MH, Lee KY, Bae SJ, Jo M, Cho JS. Intraoperative dexmedetomidine attenuates stress responses in patients undergoing major spine surgery. Minerva Anestesiol. 2019;85(5):468\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou Z, Chen Z, Gao L, Sun Q, Tang W. Effect of Minimally Invasive Internal Arch Nailing Surgery on Tissue Traumatic Stress Response in Patients with Vertebral Fractures. Contrast Media Mol Imaging. 2022;2022:2375883.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu H, Ma L. Advances in Erector Spinae Plane Block for Spinal Surgery. Acta Acad Med Sin. 2024;46(04):560\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSharma SK, Sonawane K, Mistry T. A narrative review on fascial plane blocks - Part A: Anatomical foundations and mechanistic insights. Indian J Anaesth. 2026;70(1):127\u0026ndash;36.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBehem CR, Friedheim T, Holthusen H, et al. Goal-directed colloid versus crystalloid therapy and microcirculatory blood flow following ischemia/reperfusion. Microvasc Res. 2024;152:104630.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAcharya K, Rout DK, Kapadia NA, et al. Surgical Stress Response: A Physiological Review of the Endocrine, Immune, and Metabolic Changes. Cureus. 2025;17(12):e100101.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTantri AR, Rahmi R, Marsaban AHM, Satoto D, Rahyussalim AJ, Sukmono RB. Comparison of postoperative IL-6 and IL-10 levels following Erector Spinae Plane Block (ESPB) and classical Thoracolumbar Interfascial Plane (TLIP) block in a posterior lumbar decompression and stabilization procedure: a randomized controlled trial. BMC Anesthesiol. 2023;23(1):13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Duan Y, Gao Z, Gu J. Effect of Goal-directed Fluid Therapy on the Shedding of the Glycocalyx Layer in Retroperitoneal Tumour Resection. J Coll Physicians Surg Pak. 2021;31(10):1179\u0026ndash;85.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGilbertson LE, Muhly WT, Montana MC, et al. A survey of practice in the anesthetic management of adolescent idiopathic scoliosis spine fusion by the North American Pediatric Spine Anesthesiologists Collaborative. Paediatr Anaesth. 2024;34(7):645\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu H, Xiong L, Xu X, et al. Preparation of Goal-Oriented Nano-Liquid and Its Effect of Paravertebral Nerve Block in Hemodynamics of Patients with Thoracotomy. Sci Adv Mater. 2021;13(10):1960\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu Y, Zhong M, Li S. Opioid-free anesthesia in enhanced recovery after surgery for gastrointestinal surgery: current status, challenges, and prospects. Front Pharmacol. 2025;16:1662818.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBakare AA, Varela JR, Ahn YJ, et al. Erector spinae plane block during standalone anterior lumbar surgery: impact on early ambulation, length of stay, and inpatient opioid use. J Neurosurg Spine. 2025;44(1):90\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaftalovich R, Singal A, Iskander AJ. Enhanced Recovery After Surgery (ERAS) protocols for spine surgery \u0026ndash; review of literature. Anaesthesiol Intensive Ther. 2022;54(1):71\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChe L, Yu JW, Zhang YL, et al. Intraoperative Blood Pressure Lability Acts as a Key Mediator in the Impacts of Goal-Directed Fluid Therapy on Postoperative Complications in Patients Undergoing Major Spine Surgery. Chin Med Sci J. 2023;38(4):257\u0026ndash;64.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSun Y, Liang X, Chai F, Shi D, Wang Y. Goal-directed fluid therapy using stroke volume variation on length of stay and postoperative gastrointestinal function after major abdominal surgery-a randomized controlled trial. BMC Anesthesiol. 2023;23(1):397.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"robotic surgery, goal-directed fluid therapy, erector spinae plane block, stress response, inflammation, enhanced recovery after surgery","lastPublishedDoi":"10.21203/rs.3.rs-9245316/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9245316/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Robot-assisted spine surgery, despite its minimally invasive nature, still triggers a significant surgical stress response. This study investigated whether combining goal-directed fluid therapy (GDFT) with erector spinae plane block (ESPB) could attenuate the perioperative stress response and improve recovery outcomes through modulating the neuroendocrine–inflammatory network.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In this single-center, prospective randomized trial, 80 individuals scheduled for elective robot-assisted pedicle screw fixation were allocated to either conventional fluid management under general anesthesia (control group, n=40) or a combination of GDFT and ultrasound-guided ESPB (intervention group, n=40). Primary endpoints included perioperative levels of stress indicators (cortisol [Cor], norepinephrine [NE]) and inflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-α [TNF-α], interleukin-10 [IL-10]). Secondary endpoints covered hemodynamic parameters (heart rate [HR], mean arterial pressure [MAP]), intraoperative fluid volumes, remifentanil usage, postoperative pain scores (visual analogue scale [VAS]), rescue analgesia needs, mobilization timing, hospital stay duration, and complication rates..\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Baseline demographics were balanced across groups (\u003cem\u003eP\u003c/em\u003e\u0026gt;0.05). The intervention group exhibited significantly reduced Cor, NE, and glucose levels during screw placement (T₁), at surgery conclusion (T₂), and 24 hours post-surgery (T₄) (all \u003cem\u003eP\u003c/em\u003e\u0026lt;0.05), with decreases exceeding 30% at T₁. Notably, IL-6 and TNF-α were substantially lower in the intervention group at T₂ and T₄ (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), while IL-10 concentrations were elevated (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05), indicating improved inflammatory balance. Crystalloid and colloid volumes were reduced by 24.3% and 23.5%, respectively (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), alongside a 32.1% decrease in remifentanil consumption (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). Postoperative VAS scores at 30 minutes, 24 hours, and 48 hours were markedly lower in the intervention group (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001), with a 65.6% reduction in rescue analgesia episodes (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01). Time to first ambulation (16.8±3.5 vs. 24.5±4.2 hours,\u003cem\u003e P\u003c/em\u003e\u0026lt;0.001) and postoperative hospital stay (5.2±1.1 vs. 7.1±1.4 days, \u003cem\u003eP\u003c/em\u003e\u0026lt;0.001) were significantly shortened. The incidence of postoperative nausea and vomiting (7.5% vs. 15.0%) and agitation (2.5% vs. 12.5%) were also significantly lower in the intervention group (both \u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e The combination of GDFT and ESPB effectively dampens the perioperative stress response in robot-assisted spine surgery through dual modulation of neuroendocrine activity and inflammatory pathways. This approach represents an optimized enhanced recovery after surgery (ERAS) strategy, merging precision anesthesia with advanced surgical techniques.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration:\u003c/strong\u003e Chinese Clinical Trial Registry, ChiCTR2500106739. Registered on 29 July 2025. Retrospectively registered.\u003c/p\u003e\n\u003cp\u003eThe full trial protocol is available from the corresponding author upon reasonable request.\u003c/p\u003e","manuscriptTitle":"Optimizing Perioperative Outcomes in Robot-Assisted Spine Surgery: Combined Goal-Directed Fluid Therapy and Erector Spinae Plane Block Modulates Stress and Inflammation:A Randomized Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-05-11 05:36:50","doi":"10.21203/rs.3.rs-9245316/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-13T18:52:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"311678264626658281336715393460852029623","date":"2026-05-13T18:48:01+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-10T14:44:33+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-10T09:27:18+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T11:12:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"283665812985357013918048911743600795575","date":"2026-05-06T05:28:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"215801787533012509332354949795988673420","date":"2026-05-05T04:48:44+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"181987687534140328882868755499334869888","date":"2026-04-30T09:35:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-28T08:00:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-04-26T19:28:49+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-04-07T11:01:22+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-04-07T10:30:12+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2026-04-07T08:32:22+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":"a69a830a-f637-46cf-86e0-15453e19ca65","owner":[],"postedDate":"May 11th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-13T18:52:18+00:00","index":63,"fulltext":""},{"type":"reviewerAgreed","content":"311678264626658281336715393460852029623","date":"2026-05-13T18:48:01+00:00","index":62,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-10T14:44:33+00:00","index":61,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-10T09:27:18+00:00","index":60,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-08T11:12:35+00:00","index":59,"fulltext":""},{"type":"reviewerAgreed","content":"283665812985357013918048911743600795575","date":"2026-05-06T05:28:50+00:00","index":58,"fulltext":""},{"type":"reviewerAgreed","content":"215801787533012509332354949795988673420","date":"2026-05-05T04:48:44+00:00","index":57,"fulltext":""},{"type":"reviewerAgreed","content":"181987687534140328882868755499334869888","date":"2026-04-30T09:35:55+00:00","index":41,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-05-11T05:36:50+00:00","versionOfRecord":[],"versionCreatedAt":"2026-05-11 05:36:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9245316","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9245316","identity":"rs-9245316","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}