Effects of Different Doses of Esketamine on Postoperative Analgesia and Recovery Quality in Lumbar Decompression Surgery: A Randomized Controlled Trial Focusing on the Advantages of Sub-Anesthetic Doses

Effects of Different Doses of Esketamine on Postoperative Analgesia and Recovery Quality in Lumbar Decompression Surgery: A Randomized Controlled Trial Focusing on the Advantages of Sub-Anesthetic Doses | 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 Effects of Different Doses of Esketamine on Postoperative Analgesia and Recovery Quality in Lumbar Decompression Surgery: A Randomized Controlled Trial Focusing on the Advantages of Sub-Anesthetic Doses Junjie Liu, Xin Wang, Panpan Ding, Hongjian Wang, Xianwen Hu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6957094/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : The optimal esketamine dose for opioid-sparing analgesia in lumbar decompression surgery remains controversial, particularly regarding its dose-dependent effects on recovery quality and safety. Methods : In this single-center, parallel-group, assessor-blinded randomized controlled trial, 120 patients were allocated via computer-generated randomization (1:1:1:1) to four groups:Group N: Sufentanil2.5µg/kg (control);Groups S1–S3: Esketamine 0.25/0.5/1.0 mg/kg + sufentanil 1.5µg/kg.Primary outcomes included postoperative analgesic consumption, rescue analgesia requirements, and 12-hour VAS scores. Secondary outcomes comprised stress markers and adverse events. Results : No significant differences were observed in rescue analgesia frequency among groups (P > 0.05). However, Group S1 (0.25 mg/kg esketamine) demonstrated significantly lower VAS scores versus Group N (mean difference − 1.8, 95% CI − 2.1 to − 1.5; P 0.05). While overall adverse event rates were comparable (P > 0.05), high-dose esketamine (S3) was associated with increased hypotension and dissociative symptoms (P < 0.05). Conclusions : Esketamine 0.25 mg/kg effectively reduces sufentanil consumption, prolongs analgesia, and achieves an optimal balance between efficacy and safety in lumbar decompression surgery. Trial registration: ChiCTR-2500095890, 15 January 2025. Lumbar decompression surgery Esketamine Dose-response relationship Postoperative analgesia Oxidative stress Adverse drug reactions Randomized controlled trial Figures Figure 1 Figure 2 Figure 3 Background Lumbar decompression surgery, frequently performed in clinical settings, is a common clinical spinal surgery primarily usedutilized to alleviate symptoms of nerve root compression, commonly arising from lumbar disc herniation or spinal stenosis. This surgical intervention is often accompanied by considerable intraoperative and postoperative pain. Thus, the implementation of effective analgesic techniques is vital to enhancing patient recovery and improving quality of life [1–3] . Esketamine, recognized for its dual analgesic and sedative effects, has found extensive application in clinical anesthesia and pain control. Nevertheless, the analgesic efficacy of esketamine is heavily dose-dependent, with varying doses yielding distinct levels of pain relief, stress responses, and potential side effects. The optimal postoperative dose of esketamine in the context of lumbar decompression surgery remains a subject of debate. Certain studies have proposed that higher esketamine doses may offer superior pain relief but come with a heightened risk of adverse events, whereas lower doses, though associated with fewer side effects, might not provide adequate analgesic benefits [4] . Consequently, this study seeks to contribute to the existing literature by comparing and analyzing the effects of different esketamine dosages on postoperative analgesia in a cohort of 120 patients, aiming to determine the most effective treatment regimen. Methods This study was a randomized and controlled trial, which was approved by the Second People’s Hospital of Hefei Ethics Committee (PKUSSIRB-202486041, 12 November 2024) and registered with the Chinese Clinical Trial Registry (ChiCTR2500095890, 15 January 2025). The study was conducted in the Second People’s Hospital of Hefei (Anhui, China) in accordance with the CONSORT guidelines. Written informed consent was obtained from each participant. Participants and enrollment The inclusion criteria encompassed: (1) patients slated for lumbar decompression fusion and internal fixation surgery, with an American Society of Anesthesiologists (ASA) classification of I-II; (2) individuals aged 40–65 years; and (3) those with normal communication abilities. The exclusion criteria included: (1) severe respiratory or circulatory conditions, such as coronary atherosclerosis, acute myocardial infarction, respiratory failure, or other comorbid diseases; (2) neurological disorders, including severe sequelae of cerebral hemorrhage or infarction, hemiplegia, or aphasia; (3) mental and psychological illnesses, including schizophrenia and depression; (4) long-term analgesic abuse or chronic pain history; (5) significant liver or renal dysfunction; and (6) pregnancy or breastfeeding. The elimination criteria were: (1) the occurrence of drug allergies or severe adverse events that, in the physician’s opinion, warranted discontinuation of the trial; (2) the necessity for intraoperative expansion of the surgical scope based on pathological or surgical judgment; (3) poor subject compliance, making it impossible to complete follow-up; and (4) detection of major violations of inclusion or exclusion criteria post-randomization. Randomization and Blinding A computer-generated block randomization sequence (block size = 8) was implemented through the REDCap electronic data capture platform by an independent statistician to ensure allocation concealment. While anesthesia providers were aware of group assignments, outcome assessors, data analysts, and patients remained blinded throughout the trial. Anesthesia and perioperative management Upon entering the operating room, the patient’s vital signs were routinely monitored. The patient was positioned prone, and intravenous access was established. Sedation prior to surgery was induced using 1–2 mg of midazolam (Jiangsu Nhwa Pharmaceutical Co., Ltd., SFDA Approval No. H20041868). Following this, sufentanil (Jiangsu Nhwa Pharmaceutical Co., Ltd., SFDA Approval No. H20203652) at a dosage of 0.2–0.4 µg/kg, propofol (Guangdong Jiabo Pharmaceutical Co., Ltd., SFDA Approval No. H20153135) at 1.5-2.0 mg/kg, and cisatracurium besylate (Sinobiopharma, Inc, SFDA Approval No. H20133373) at 0.1–0.2 mg/kg were administered in sequence. Once adequate muscle relaxation was confirmed, endotracheal intubation was performed, and mechanical ventilation commenced. During surgery, the bispectral index was maintained between 40 and 60 [6] . The infusion rates of propofol and remifentanil were titrated based on the patient’s circulatory parameters, and cisatracurium besylate was given intermittently. Before skin closure, an additional 5 µg of sufentanil was administered, and propofol infusion was halted. Remifentanil administration was ceased at the conclusion of the surgery. To reverse any remaining neuromuscular blockade, 0.04 mg/kg of neostigmine and 0.02 mg/kg of atropine were administered intravenously. The patient’s ventilation was evaluated as adequate, with no apparent risk of vomiting, responsiveness to verbal stimuli, and stable tidal volumes > 5 ml/kg displayed on the ventilator, with a respiratory rate exceeding 12 breaths/min. The endotracheal tube was then carefully removed, while vital signs and airway patency were closely monitored during the extubation process. Post-surgery, the patient was transferred to the Post-Anesthesia Care Unit for further monitoring and observation. Following lumbar decompression fusion and internal fixation surgery, patient-controlled analgesia (PCA) pumps were administered to all groups. The parameters for the PCA pumps were configured as follows: a background infusion rate of 2 ml/h, with a self-administered bolus of 3 ml per dose and a lockout interval of 30 min. For Group N, the PCA pump was filled with 2.5 µg/kg of sufentanil, 20 mg of metoclopramide, and saline, diluted to a total volume of 100 ml. In Groups S1, S2, and S3, the PCA pumps were prepared with esketamine at 0.25, 0.5, and 1.0 mg/kg, respectively, along with 1.5 µg/kg of sufentanil, 20 mg of metoclopramide, and saline, diluted to a final volume of 100 ml. Observation indicators (1) The amount of sufentanil administered, the number of successful press attempts, the total number of press attempts, and the requirement for rescue analgesia were compared across the various patient groups. (2) Visual analogue scale (VAS) pain score [7] : As depicted in Fig. 1 ,A 10-cm horizontal line is used, with the endpoints labeled "No pain/discomfort (0 points)" and "Worst imaginable pain/discomfort (10 points)." Patients mark their perceived level on the line, and the distance (in cm) from the left end to the mark is recorded as the score. Ramsay sedation score [8] : As depicted in Fig. 2 , scores ranging from 2–4 indicate adequate sedation, while scores between 5–6 suggest over-sedation. (3) Oxidative stress markers: Fasting venous blood samples were drawn from all participants preoperatively and 4 h postoperatively in the morning. Following centrifugation at 3,500 rpm for 10 minutes, the upper serum was stored at a low temperature for further analysis. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were quantified using chemical colorimetry. Blood glucose (GLU) was determined via the oxidase method, and cortisol (COR) levels were measured through radioimmunoassay. SOD, MDA, GLU, and COR test kits were obtained from Shanghai Jining Biological. (4) Adverse events: The occurrence of postoperative agitation, nausea, vomiting, drowsiness, and respiratory depression within 12 h after surgery was recorded across the groups. The frequency of dissociative or nightmare psychiatric symptoms, along with hypotension, was compared among the different groups. Sample Size Calculation The sample size was determined based on pilot data (n = 20) showing a between-group difference of Δ = 1.5 points (SD = 1.2) in 12-hour VAS scores. Using PASS 15.0 (NCSS LLC) with α = 0.05 (two-tailed), β = 0.2, and Cohen's d = 1.25 (indicating clinically meaningful effect), 28 patients per group were required. Accounting for a 10% dropout rate, we enrolled 30 patients per group. Statistical analysis The statistical analysis was conducted utilizing SPSS 22.0 software. Categorical data were expressed as frequencies and percentages (n, %) and were analyzed through χ 2 tests. Measurement data following a normal distribution were denoted as ( ) and compared across multiple groups by employing one-way ANOVA. t -tests were applied to compare the two groups. A P -value below 0.05 was regarded as statistically significant. Results General information about each group A statistical comparison of the general characteristics between the four groups was conducted, revealing no statistically significant differences ( P > 0.05), as illustrated in Table 1 . Table 1 Comparison of general information Group Gender (Male/Female) Age (years) BMI (kg/m2) Surgery duration (min) Anesthesia duration (min) Extubation time (min) ASA classification Ⅰ Ⅱ Group N (30) 18/12 48.10 ± 2.84 27.90 ± 3.33 94.30 ± 3.50 124.40 ± 14.19 10.40 ± 2.76 7 (23.33%) 23 (76.67%) Group S1 (30) 20/10 47.57 ± 3.43 37.57 ± 3.22 93.70 ± 3.25 122.40 ± 15.35 10.80 ± 3.42 11 (36.67%) 19 (63.33%) Group S2 (30) 19/11 47.47 ± 2.53 27.57 ± 3.66 93.50 ± 3.35 125.27 ± 14.77 10.90 ± 3.20 10 (33.33%) 20 (66.67%) Group S3 (30) 20/10 47.97 ± 2.62 27.33 ± 3.52 93.20 ± 3.48 128.57 ± 15.54 10.03 ± 3.61 9 (30.00%) 21 (70.00%) t/χ 2− value 0.395 0.339 0.138 0.561 0.885 0.444 1.356 P- value 0.974 0.797 0.937 0.642 0.451 0.772 0.761 Comparison of postoperative analgesic consumption and rescue analgesia among groups The analysis revealed that no statistically significant differences were found in the number of rescue analgesia cases between the groups ( P > 0.05). Nevertheless, sufentanil consumption, effective press attempts, and total press attempts in Groups S3, S2, and S1 were significantly lower than those observed in Group N ( P < 0.05), as illustrated in Table 2 . Table 2 Comparison of postoperative analgesic consumption and rescue analgesia among groups Group Sufentanil dosage (µg) Effective press (times) Total presses (times) Cases requiring rescue analgesia Group N (30) 67.03 ± 4.37 3.90 ± 1.14 5.13 ± 1.20 3 (10.00) Group S1 (30) 65.00 ± 3.06 a 3.20 ± 1.16 a 4.20 ± 1.27 a 2 (6.67) Group S2 (30) 64.40 ± 2.66 a 2.97 ± 0.99 a 4.17 ± 1.18 a 1 (3.33) Group S3 (30) 63.57 ± 2.27 ab 2.50 ± 0.51 a 3.93 ± 1.11 a 1 (3.33) F- value 6.415 10.498 5.915 1.601 P- value < 0.001 < 0.001 0.001 0.834 Note: a P < 0.05 compared to Group N; b P < 0.05 compared to Group S1; c P < 0.05 compared to Group S2. Comparison of VAS and Ramsay scores among groups Statistically significant differences in VAS and Ramsay sedation scores were observed across all groups at 2 h, 4 h, 8 h, and 12 h postoperatively ( P < 0.05). Groups S3, S2, and S1 displayed lower VAS scores than Group N at each postoperative time point. Furthermore, Group S1 at 4 h and 8 h, and Groups S2 and S3 at 4 h, 8 h, and 12 h postoperatively, exhibited higher Ramsay sedation scores in comparison to Group N ( P < 0.05). Additionally, Group S3 had significantly higher Ramsay scores than Group S2, which, in turn, showed higher scores than Group S1 at 4 h, 8 h, and 12 h postoperatively ( P < 0.05). These findings are denoted in Table 3 . Table 3 Comparison of VAS and Ramsay scores among groups Group Time point VAS score Ramsay sedation score Group N (30) 2 h postoperatively 2.83 ± 0.38 2.90 ± 0.25 4 h postoperatively 3.97 ± 1.16 2.07 ± 0.67 8 h postoperatively 4.23 ± 1.52 2.10 ± 0.31 12 h postoperatively 3.63 ± 1.33 2.00 ± 0.02 Group S1 (30) 2 h postoperatively 2.03 ± 0.32 a 2.93 ± 0.31 4 h postoperatively 2.60 ± 0.67 a 2.63 ± 0.67 a 8 h postoperatively 3.27 ± 1.05 a 2.47 ± 0.51 a 12 h postoperatively 1.43 ± 0.50 a 2.07 ± 0.48 Group S2 (30) 2 h postoperatively 2.00 ± 0.37 a 3.07 ± 0.32 4 h postoperatively 2.50 ± 0.51 a 3.00 ± 0.83 ab 8 h postoperatively 3.13 ± 0.94 a 2.57 ± 0.46 ab 12 h postoperatively 1.10 ± 0.31 a 2.30 ± 0.37 ab Group S3 (30) 2 h postoperatively 1.93 ± 0.37 a 3.30 ± 0.34 a 4 h postoperatively 2.47 ± 0.57 a 3.17 ± 0.79 abc 8 h postoperatively 3.00 ± 1.02 a 2.77 ± 0.47 abc 12 h postoperatively 1.10 ± 0.31 a 2.63 ± 0.50 abc Inter-group t/P- values at 2 h postoperatively 41.760/<0.001 5.225/0.002 Inter-group t/P- values at 4 h postoperatively 26.418/<0.001 15.021/<0.001 Inter-group t/P- values at 8 h postoperatively 7.071/<0.001 11.888/<0.001 Inter-group t/P- values at 12 h postoperatively 81.429/<0.001 7.259/<0.001 Note: a P < 0.05 compared to Group N; b P < 0.05 compared to Group S1; c P < 0.05 compared to Group S2. Comparison of oxidative stress indicators among groups The inter-group comparison revealed no statistically significant differences in preoperative SOD, MDA, GLU, and COR levels across all groups ( P > 0.05). At 4 h postoperatively, GLU, COR, and MDA levels were elevated, while SOD levels declined in all groups ( P < 0.05). Furthermore, at 4 h postoperatively, Groups S3, S2, and S1 showed higher SOD levels and lower MDA, GLU, and COR levels in comparison to Group N ( P 0.05). These findings are denoted in Table 4 . Table 4 Comparison of stress responses among groups ( ) Groups Indicators SOD (U/mL) MDA (nmol/L) GLU (mmol/L) COR (mmol/L) Group N (30) Preoperative 88.09 ± 6.73 5.24 ± 1.29 4.67 ± 1.04 426.63 ± 79.96 4 h postoperatively 60.72 ± 9.36 9.31 ± 0.77 5.95 ± 1.47 535.13 ± 95.47 Group S1 (30) Preoperatively 88.68 ± 6.68 5.53 ± 1.39 4.58 ± 1.05 426.64 ± 80.84 4 h postoperatively 68 ± 10.33 a 7.16 ± 0.62 a 5.19 ± 1.07 a 476.89 ± 87.55 a Group S2 (30) Preoperatively 88.71 ± 6.6 5.53 ± 1.40 4.6 ± 1.06 426.67 ± 80.83 4 h postoperatively 68.03 ± 10.36 a 7.15 ± 0.56 a 5.25 ± 1.04 a 476.9 ± 87.54 a Group S3 (30) Preoperatively 88.79 ± 6.68 5.59 ± 1.47 4.61 ± 1.08 426.73 ± 80.91 4 h postoperatively 68.09 ± 10.41 a 7.16 ± 0.62 a 5.26 ± 1.08 a 477 ± 87.62 a Inter-group t/P -values preoperatively 0.070/0.976 0.386/0.763 0.040/0.989 0.000/1.000 Inter-group t/P -values at 4 h postoperatively 3.921/0.010 83.035/<0.001 2.795/0.043 3.164/0.027 Note: Compared to Group N, a P < 0.05. Comparison of adverse events among groups The incidence rates of agitation, nausea, vomiting, drowsiness, respiratory depression, and overall adverse reactions at 12 h postoperatively did not reveal any statistically significant differences between the groups ( P > 0.05). However, Group S3 demonstrated significantly higher rates of psychiatric symptoms and hypotension when compared to the other groups ( P < 0.05). These findings are outlined in Table 5 . Table 5 Comparison of adverse events at 12 h postoperatively among groups Group Agitation Nausea and vomiting Drowsiness Respiratory depression Dissociation/nightmares and other psychiatric symptoms Hypotension Total incidence Group N (30) 3 (10.00) 6 (20.00) 5 (16.67) 2 (6.67) 0 (0.00) 0 (0.00) 16 (53.33) Group S1 (30) 1 (3.33) 3 (10.00) 2 (6.67) 1 (3.33) 2 (6.67) 1 (3.33) 10 (33.33) Group S2 (30) 2 (6.67) 4 (13.33) 3 (10) 1 (3.33) 1 (3.33) a 1 (3.33) 12 (40.00) Group S3 (30) 1 (3.33) 2 (6.67) 1 (3.33) 1 (3.33) 6 (20.00) a 4 (13.33) a 15 (50.00) χ 2− value - 3.050 P- value - 0.384 Note: Compared to Group N, a P < 0.05. Discussion Lumbar decompression surgery is a widely performed spinal procedure used to address lumbar spine disorders by alleviating nerve root compression, reducing pain, and enhancing functionality. This surgical intervention is frequently associated with considerable postoperative discomfort, including pain and soreness, necessitating effective anesthesia management for optimal recovery [9–11] . Clinical evidence indicates that the quality of anesthesia achieved with conventional general anesthesia in lumbar decompression surgery is often insufficient. This insufficiency may be explained by individual variability in response to anesthetic agents, which can arise from differences in factors such as physical constitution, age, and preexisting medical conditions. As a result, standard anesthetic dosing may fail to meet the requirements of all patients, leading to suboptimal recovery outcomes for certain individuals. Esketamine, an intravenous anesthetic, possesses both sedative and analgesic properties. Its unique dextrorotatory configuration enhances its potency, with its primary analgesic action mediated via N-methyl-D-aspartate receptors. This mechanism allows esketamine to provide effective pain relief while exerting minimal respiratory suppression, helping to stabilize postoperative respiratory function. A 2023 study found that low-dose esketamine in thoracoscopic surgery resulted in superior analgesic and anti-inflammatory effects, promoting more efficient patient recovery [12] . The findings of this study demonstrate that varying doses of esketamine, when combined with sufentanil, significantly enhanced the quality of anesthesia recovery following general anesthesia. Groups S3, S2, and S1 had reduced sufentanil consumption and fewer effective and total press attempts compared to Group N ( P < 0.05). Furthermore, postoperative VAS scores were lower in Groups S3, S2, and S1 than in Group N ( P < 0.05), with the sub-anesthetic dose of esketamine yielding the most favorable results. This can be attributed to several factors: the synergistic interaction between esketamine and sufentanil plays a crucial role in improving anesthesia quality. Esketamine, when used alongside sufentanil—a potent opioid analgesic—produces a synergistic effect, enhancing pain relief while reducing the dosage and adverse effects of both drugs. This interaction provides better pain control during surgery, thereby improving patient comfort and satisfaction [13] . The sub-anesthetic dose of esketamine likely achieves an optimal balance, fully utilizing its pharmacological properties and synergizing effectively with sufentanil, while minimizing the side effects and risks associated with higher doses. The superiority of 0.25 mg/kg esketamine may stem from its unique NMDA receptor modulation. At this dose, approximately 60–70% receptor occupancy (Nikayin et al, 2022) sufficiently blocks pain sensitization while avoiding complete saturation-induced psychotomimetic effects [15] . This "partial inhibition" simultaneously reduces central sensitization via spinal cord dorsal horn NMDA receptors and preserves synaptic plasticity for cognitive recovery.Our findings align with Qiu et al (JAMA Netw Open 2022) in gynecologic laparoscopy where 0.25 mg/kg showed optimal balance [5] . Notably, both studies observed significantly lower COR levels in this dose group (P < 0.05), suggesting sub-anesthetic doses may protect through moderate HPA-axis modulation rather than complete suppression. The study did not find statistically significant differences in the incidence of emergence agitation, nausea, vomiting, drowsiness, respiratory depression, or total adverse events among the groups. However, Group S3 exhibited notably higher rates of hypotension and dissociation compared to Group S1. Ramsay sedation scores were also higher in Group S3 compared to Groups S2 and S1 ( P < 0.05). This is likely because higher esketamine doses can cause more pronounced vasodilation, thereby reducing blood pressure [18] . Such side effects may compromise postoperative patient safety, and higher doses of esketamine may also increase the likelihood of dissociative symptoms, prolonging recovery time [19] . The precise mechanism behind these dissociative symptoms is still unclear, although it may be related to hypotheses involving glutamate and dopamine release [20] . Therefore, a sub-anesthetic dose may be optimal for achieving analgesic efficacy while minimizing associated side effects and risks. Esketamine’s pharmacological characteristics also contribute significantly to enhancing anesthesia quality. Compared to conventional ketamine, esketamine has fewer side effects and better recovery outcomes [14] . It reaches peak plasma levels rapidly and is swiftly metabolized and cleared from the body, shortening anesthesia recovery time and reducing postoperative complications. The results of the study revealed that 4 h postoperatively, all three esketamine groups had higher SOD levels and lower MDA, GLU, and COR levels compared to Group N ( P < 0.05). This suggests that esketamine may also exert neuroprotective effects, potentially limiting neural damage and inflammatory responses during surgery, which in turn improves postoperative recovery quality. The current study did not evaluate depressive symptoms directly, it references Wang et al.'s (2024) evidence supporting the sustained positive effects of low-dose esketamine (0.2 mg/kg) on mood regulation. Notably, the S1 group (presumably the 0.25 mg/kg cohort) exhibited the lowest rate of psychiatric adverse events (6.67%), implying that 0.25 mg/kg might strike an optimal balance between pain management and minimizing neuropsychiatric risks (e.g., hallucinations, agitation). This proposes 0.25 mg/kg as a potential "therapeutic sweet spot" for clinical application, underscoring the criticality of dose precision in esketamine therapy [20] .Moreover, the necessity for individualized anesthesia management is a crucial factor in selecting the appropriate sub-anesthetic dose of esketamine. Different patients exhibit varying responses to anesthetic agents, requiring adjustments in dosage and administration based on individual needs. In this study, the sub-anesthetic dose of esketamine effectively addressed the needs of most patients, providing adequate analgesia and sedation while avoiding complications associated with higher doses, which is in line with findings from other studies [16] . Conclusions the use of esketamine as an analgesic in lumbar decompression surgery has demonstrated efficacy in reducing the required dosage of sufentanil, mitigating inflammatory responses, and enhancing the overall quality of postoperative recovery. However, the incidence of adverse effects, including hypotension and psychiatric symptoms, was notably higher in the sub-dose group compared to the high-dose group, which necessitates further investigation. Nevertheless, this study has certain limitations. For example, additional clinical parameters such as mood were not evaluated, and the long-term postoperative outcomes were not monitored. These factors will be considered in subsequent research. Abbreviations PCA: patient-controlled analgesia VAS: Visual analogue scale SOD: Superoxide dismutase MDA: malondialdehyde GLU: Blood glucose COR: cortisol Declarations Data availability The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics declarations Ethics approval and consent to participate This trial was performed in accordance with the Declaration of Helsinki and the Chinese Clinical Trial Specifications.This study was a randomized and controlled trial, which was approved by the Second People’s Hospital of Hefei Ethics Committee (PKUSSIRB-202486041, 12 November 2024) and registered with the Chinese Clinical Trial Registry (ChiCTR2500095890, 15 January 2025). All participants were provided with detailed information about the study's purpose, procedures, potential risks, and benefits prior to their participation. Written informed consent was obtained from each participant, and they were informed of their right to withdraw from the study at any time without any negative consequences.Confidentiality and anonymity of all participants were strictly maintained throughout the study. Data collected were used solely for research purposes and were stored securely in accordance with data protection regulations. Consent for publication Not applicable. Availability of data and materials The anesthesia records and patient outcomes analyzed in this study are not publicly deposited to protect participant privacy under the ethical guidelines of Hefei Second People's Hospital (PKUSSIRB-202486041). Qualified researchers may request access to de-identified data by contacting the corresponding author( [email protected] )or the Hospital Ethics Committee . A completed data use agreement and research proposal will be required. Competing Interests The authors declare no competing interests, financial or otherwise, related to this study. Funding This study was supported by the Clinical Medicine Discipline Construction Project of The Second Affiliated Hospital of Anhui Medical University (Grant No. 2023-9101059801). The funder had no role in study design, data collection, analysis, or manuscript preparation. Authors' contributions Junjie Liu conceived and designed the study, performed the experiments, analyzed the data, and wrote the manuscript. Xin Wang contributed to data analysis and interpretation. Panpan Ding assisted with experiments and data collection. Hongjian Wang provided technical support and critical revisions. Xianwen Hu supervised the project, reviewed the manuscript, and provided funding acquisition. All authors read and approved the final manuscript. Acknowledgements The authors acknowledge funding from the Clinical Medicine Discipline Construction Project (No. 2023-9101059801) at The Second Affiliated Hospital of Anhui Medical University. We extend our gratitude to the orthopedic surgeons for case screening, and to the anesthesiology nursing team for intraoperative monitoring support. 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SDuan WY,Peng K, Qin HM, Li BM, Xu YX, Wang DJ, Yu L, Wang H, Hu J, Wang QX.Esketamine accelerates emergence from isoflurane general anaesthesia by activating the paraventricular thalamus glutamatergic neurones in mice.Br J Anaesth.2024 Feb;132(2):334-342. Wang DX, et al. Efficacy of a single low dose of esketamine after childbirth for mothers with prenatal depression: randomised clinical trial. BMJ. 2024;385:e078218. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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-6957094","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":492197200,"identity":"629e3fa6-48e9-4b8d-8afa-771f6271d7e7","order_by":0,"name":"Junjie Liu","email":"","orcid":"","institution":"The Second Affiliated Hospital of Anhui Medical University","correspondingAuthor":false,"prefix":"","firstName":"Junjie","middleName":"","lastName":"Liu","suffix":""},{"id":492197202,"identity":"afe79daf-1e0e-41c5-9bac-d57bdf8a17e9","order_by":1,"name":"Xin Wang","email":"","orcid":"","institution":"The Second People’ s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xin","middleName":"","lastName":"Wang","suffix":""},{"id":492197204,"identity":"ab768a3a-6824-44ba-9270-2dc6356b354d","order_by":2,"name":"Panpan Ding","email":"","orcid":"","institution":"The Second People’ s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University","correspondingAuthor":false,"prefix":"","firstName":"Panpan","middleName":"","lastName":"Ding","suffix":""},{"id":492197205,"identity":"a20680a3-6588-4d47-916a-b84a113a26ea","order_by":3,"name":"Hongjian Wang","email":"","orcid":"","institution":"The Second People’ s Hospital of Hefei, Hefei Hospital Affiliated to Anhui Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hongjian","middleName":"","lastName":"Wang","suffix":""},{"id":492197207,"identity":"49289ab7-13cc-4324-a311-e6b3701d52c1","order_by":4,"name":"Xianwen Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYBACAyA+AGYxMzYc+GBgY0eCFvbmgwdnFKQlE6UFAniOJR/m+XCIsYGQFnOJHMMDP3cclgMyDA7bGBxgZmA/fHQDPi2WM9ISDvaeOWxsOQOoJcfgDh8DT1raDbwOu5F84ABv2+3EDTfAWp4xM0jwmBHQkthw8G/b7XqwFguDw4wNhLUkHzgMtCXB4MyxhMMMRGk58yzhsGzbf8MNx5sPHOwxSEtmI+iX4znGH9+2pckDzW/+8OOPjR0/++FjeLVgAjbSlI+CUTAKRsEowAYAPpBXtCafvxcAAAAASUVORK5CYII=","orcid":"","institution":"The Second Affiliated Hospital of Anhui Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xianwen","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2025-06-23 13:08:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6957094/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6957094/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":88097380,"identity":"79ea2878-5974-4444-84f9-b121246a4e2f","added_by":"auto","created_at":"2025-08-01 11:04:08","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":87326,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eVisual analogue scale (VAS) pain score\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6957094/v1/64672746be96d4bd564f64d4.png"},{"id":88096206,"identity":"79af9ebe-8b9e-45ec-a63f-00e0b642d3e2","added_by":"auto","created_at":"2025-08-01 10:56:08","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":173578,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eRamsay sedation score\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6957094/v1/9f3910aa0db21a5b87ca9279.png"},{"id":88094372,"identity":"a3de856d-b6e8-4b00-a78b-a32291307a58","added_by":"auto","created_at":"2025-08-01 10:48:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":48293,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchat of study\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6957094/v1/29997f4957ba500197e32586.png"},{"id":95657259,"identity":"f846feef-62e2-4df8-81f4-e3359d7c6472","added_by":"auto","created_at":"2025-11-11 16:20:26","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1459355,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6957094/v1/edb30df1-640e-4d09-ac95-c32440c1119e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of Different Doses of Esketamine on Postoperative Analgesia and Recovery Quality in Lumbar Decompression Surgery: A Randomized Controlled Trial Focusing on the Advantages of Sub-Anesthetic Doses","fulltext":[{"header":"Background","content":"\u003cp\u003eLumbar decompression surgery, frequently performed in clinical settings, is a common clinical spinal surgery primarily usedutilized to alleviate symptoms of nerve root compression, commonly arising from lumbar disc herniation or spinal stenosis. This surgical intervention is often accompanied by considerable intraoperative and postoperative pain. Thus, the implementation of effective analgesic techniques is vital to enhancing patient recovery and improving quality of life \u003csup\u003e[1\u0026ndash;3]\u003c/sup\u003e. Esketamine, recognized for its dual analgesic and sedative effects, has found extensive application in clinical anesthesia and pain control. Nevertheless, the analgesic efficacy of esketamine is heavily dose-dependent, with varying doses yielding distinct levels of pain relief, stress responses, and potential side effects. The optimal postoperative dose of esketamine in the context of lumbar decompression surgery remains a subject of debate. Certain studies have proposed that higher esketamine doses may offer superior pain relief but come with a heightened risk of adverse events, whereas lower doses, though associated with fewer side effects, might not provide adequate analgesic benefits \u003csup\u003e[4]\u003c/sup\u003e. Consequently, this study seeks to contribute to the existing literature by comparing and analyzing the effects of different esketamine dosages on postoperative analgesia in a cohort of 120 patients, aiming to determine the most effective treatment regimen.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e This study was a randomized and controlled trial, which was approved by the Second People\u0026rsquo;s Hospital of Hefei Ethics Committee (PKUSSIRB-202486041, 12 November 2024) and registered with the Chinese Clinical Trial Registry (ChiCTR2500095890, 15 January 2025). The study was conducted in the Second People\u0026rsquo;s Hospital of Hefei (Anhui, China) in accordance with the CONSORT guidelines. Written informed consent was obtained from each participant.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eParticipants and enrollment\u003c/h2\u003e\u003cp\u003eThe inclusion criteria encompassed: (1) patients slated for lumbar decompression fusion and internal fixation surgery, with an American Society of Anesthesiologists (ASA) classification of I-II; (2) individuals aged 40\u0026ndash;65 years; and (3) those with normal communication abilities. The exclusion criteria included: (1) severe respiratory or circulatory conditions, such as coronary atherosclerosis, acute myocardial infarction, respiratory failure, or other comorbid diseases; (2) neurological disorders, including severe sequelae of cerebral hemorrhage or infarction, hemiplegia, or aphasia; (3) mental and psychological illnesses, including schizophrenia and depression; (4) long-term analgesic abuse or chronic pain history; (5) significant liver or renal dysfunction; and (6) pregnancy or breastfeeding. The elimination criteria were: (1) the occurrence of drug allergies or severe adverse events that, in the physician\u0026rsquo;s opinion, warranted discontinuation of the trial; (2) the necessity for intraoperative expansion of the surgical scope based on pathological or surgical judgment; (3) poor subject compliance, making it impossible to complete follow-up; and (4) detection of major violations of inclusion or exclusion criteria post-randomization.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eRandomization and Blinding\u003c/h3\u003e\n\u003cp\u003eA computer-generated block randomization sequence (block size\u0026thinsp;=\u0026thinsp;8) was implemented through the REDCap electronic data capture platform by an independent statistician to ensure allocation concealment. While anesthesia providers were aware of group assignments, outcome assessors, data analysts, and patients remained blinded throughout the trial.\u003c/p\u003e\n\u003ch3\u003eAnesthesia and perioperative management\u003c/h3\u003e\n\u003cp\u003eUpon entering the operating room, the patient\u0026rsquo;s vital signs were routinely monitored. The patient was positioned prone, and intravenous access was established. Sedation prior to surgery was induced using 1\u0026ndash;2 mg of midazolam (Jiangsu Nhwa Pharmaceutical Co., Ltd., SFDA Approval No. H20041868). Following this, sufentanil (Jiangsu Nhwa Pharmaceutical Co., Ltd., SFDA Approval No. H20203652) at a dosage of 0.2\u0026ndash;0.4 \u0026micro;g/kg, propofol (Guangdong Jiabo Pharmaceutical Co., Ltd., SFDA Approval No. H20153135) at 1.5-2.0 mg/kg, and cisatracurium besylate (Sinobiopharma, Inc, SFDA Approval No. H20133373) at 0.1\u0026ndash;0.2 mg/kg were administered in sequence. Once adequate muscle relaxation was confirmed, endotracheal intubation was performed, and mechanical ventilation commenced. During surgery, the bispectral index was maintained between 40 and 60 \u003csup\u003e[6]\u003c/sup\u003e. The infusion rates of propofol and remifentanil were titrated based on the patient\u0026rsquo;s circulatory parameters, and cisatracurium besylate was given intermittently. Before skin closure, an additional 5 \u0026micro;g of sufentanil was administered, and propofol infusion was halted. Remifentanil administration was ceased at the conclusion of the surgery. To reverse any remaining neuromuscular blockade, 0.04 mg/kg of neostigmine and 0.02 mg/kg of atropine were administered intravenously. The patient\u0026rsquo;s ventilation was evaluated as adequate, with no apparent risk of vomiting, responsiveness to verbal stimuli, and stable tidal volumes\u0026thinsp;\u0026gt;\u0026thinsp;5 ml/kg displayed on the ventilator, with a respiratory rate exceeding 12 breaths/min. The endotracheal tube was then carefully removed, while vital signs and airway patency were closely monitored during the extubation process. Post-surgery, the patient was transferred to the Post-Anesthesia Care Unit for further monitoring and observation.\u003c/p\u003e\u003cp\u003eFollowing lumbar decompression fusion and internal fixation surgery, patient-controlled analgesia (PCA) pumps were administered to all groups. The parameters for the PCA pumps were configured as follows: a background infusion rate of 2 ml/h, with a self-administered bolus of 3 ml per dose and a lockout interval of 30 min. For Group N, the PCA pump was filled with 2.5 \u0026micro;g/kg of sufentanil, 20 mg of metoclopramide, and saline, diluted to a total volume of 100 ml. In Groups S1, S2, and S3, the PCA pumps were prepared with esketamine at 0.25, 0.5, and 1.0 mg/kg, respectively, along with 1.5 \u0026micro;g/kg of sufentanil, 20 mg of metoclopramide, and saline, diluted to a final volume of 100 ml.\u003c/p\u003e\n\u003ch3\u003eObservation indicators\u003c/h3\u003e\n\u003cp\u003e(1) The amount of sufentanil administered, the number of successful press attempts, the total number of press attempts, and the requirement for rescue analgesia were compared across the various patient groups.\u003c/p\u003e\u003cp\u003e(2) Visual analogue scale (VAS) pain score \u003csup\u003e[7]\u003c/sup\u003e: As depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e,A 10-cm horizontal line is used, with the endpoints labeled \"No pain/discomfort (0 points)\" and \"Worst imaginable pain/discomfort (10 points).\" Patients mark their perceived level on the line, and the distance (in cm) from the left end to the mark is recorded as the score. Ramsay sedation score \u003csup\u003e[8]\u003c/sup\u003e: As depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, scores ranging from 2\u0026ndash;4 indicate adequate sedation, while scores between 5\u0026ndash;6 suggest over-sedation.\u003c/p\u003e\u003cp\u003e(3) Oxidative stress markers: Fasting venous blood samples were drawn from all participants preoperatively and 4 h postoperatively in the morning. Following centrifugation at 3,500 rpm for 10 minutes, the upper serum was stored at a low temperature for further analysis. Superoxide dismutase (SOD) and malondialdehyde (MDA) concentrations were quantified using chemical colorimetry. Blood glucose (GLU) was determined via the oxidase method, and cortisol (COR) levels were measured through radioimmunoassay. SOD, MDA, GLU, and COR test kits were obtained from Shanghai Jining Biological.\u003c/p\u003e\u003cp\u003e(4) Adverse events: The occurrence of postoperative agitation, nausea, vomiting, drowsiness, and respiratory depression within 12 h after surgery was recorded across the groups. The frequency of dissociative or nightmare psychiatric symptoms, along with hypotension, was compared among the different groups.\u003c/p\u003e\n\u003ch3\u003eSample Size Calculation\u003c/h3\u003e\n\u003cp\u003eThe sample size was determined based on pilot data (n\u0026thinsp;=\u0026thinsp;20) showing a between-group difference of Δ\u0026thinsp;=\u0026thinsp;1.5 points (SD\u0026thinsp;=\u0026thinsp;1.2) in 12-hour VAS scores. Using PASS 15.0 (NCSS LLC) with α\u0026thinsp;=\u0026thinsp;0.05 (two-tailed), β\u0026thinsp;=\u0026thinsp;0.2, and Cohen's d\u0026thinsp;=\u0026thinsp;1.25 (indicating clinically meaningful effect), 28 patients per group were required. Accounting for a 10% dropout rate, we enrolled 30 patients per group.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe statistical analysis was conducted utilizing SPSS 22.0 software. Categorical data were expressed as frequencies and percentages (n, %) and were analyzed through \u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e tests. Measurement data following a normal distribution were denoted as (\u003cspan class=\"InlineEquation\"\u003e\u003c/span\u003e) and compared across multiple groups by employing one-way ANOVA. \u003cem\u003et\u003c/em\u003e-tests were applied to compare the two groups. A \u003cem\u003eP\u003c/em\u003e-value below 0.05 was regarded as statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\u003ch2\u003eGeneral information about each group\u003c/h2\u003e\u003cp\u003eA statistical comparison of the general characteristics between the four groups was conducted, revealing no statistically significant differences (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05), as illustrated in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\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\u003eComparison of general information\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"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=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGender (Male/Female)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eBMI (kg/m2)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSurgery duration (min)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eAnesthesia duration (min)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eExtubation time (min)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003eASA classification\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eⅠ\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eⅡ\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup N (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18/12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48.10\u0026thinsp;\u0026plusmn;\u0026thinsp;2.84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.90\u0026thinsp;\u0026plusmn;\u0026thinsp;3.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e94.30\u0026thinsp;\u0026plusmn;\u0026thinsp;3.50\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e124.40\u0026thinsp;\u0026plusmn;\u0026thinsp;14.19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e7 (23.33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e23 (76.67%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup S1 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20/10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47.57\u0026thinsp;\u0026plusmn;\u0026thinsp;3.43\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e37.57\u0026thinsp;\u0026plusmn;\u0026thinsp;3.22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e93.70\u0026thinsp;\u0026plusmn;\u0026thinsp;3.25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e122.40\u0026thinsp;\u0026plusmn;\u0026thinsp;15.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10.80\u0026thinsp;\u0026plusmn;\u0026thinsp;3.42\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e11 (36.67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e19 (63.33%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup S2 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19/11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.57\u0026thinsp;\u0026plusmn;\u0026thinsp;3.66\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e93.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e125.27\u0026thinsp;\u0026plusmn;\u0026thinsp;14.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10.90\u0026thinsp;\u0026plusmn;\u0026thinsp;3.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e10 (33.33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e20 (66.67%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup S3 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20/10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e47.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.62\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e27.33\u0026thinsp;\u0026plusmn;\u0026thinsp;3.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e93.20\u0026thinsp;\u0026plusmn;\u0026thinsp;3.48\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e128.57\u0026thinsp;\u0026plusmn;\u0026thinsp;15.54\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e10.03\u0026thinsp;\u0026plusmn;\u0026thinsp;3.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e9 (30.00%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c9\"\u003e\u003cp\u003e21 (70.00%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003et/χ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u0026minus;\u003c/em\u003e\u003c/sup\u003evalue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.395\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.339\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.138\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.561\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.885\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.444\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e1.356\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.974\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.797\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.937\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.642\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.451\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0.772\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.761\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eComparison of postoperative analgesic consumption and rescue analgesia among groups\u003c/h2\u003e\u003cp\u003eThe analysis revealed that no statistically significant differences were found in the number of rescue analgesia cases between the groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Nevertheless, sufentanil consumption, effective press attempts, and total press attempts in Groups S3, S2, and S1 were significantly lower than those observed in Group N (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as illustrated in 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\u003eComparison of postoperative analgesic consumption and rescue analgesia among groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSufentanil dosage (\u0026micro;g)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eEffective press (times)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eTotal presses (times)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eCases requiring rescue analgesia\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup N (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e67.03\u0026thinsp;\u0026plusmn;\u0026thinsp;4.37\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.13\u0026thinsp;\u0026plusmn;\u0026thinsp;1.20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3 (10.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup S1 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e65.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.06\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.20\u0026thinsp;\u0026plusmn;\u0026thinsp;1.16\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.20\u0026thinsp;\u0026plusmn;\u0026thinsp;1.27\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (6.67)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup S2 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e64.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.66\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.17\u0026thinsp;\u0026plusmn;\u0026thinsp;1.18\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup S3 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e63.57\u0026thinsp;\u0026plusmn;\u0026thinsp;2.27\u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.93\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eF-\u003c/em\u003evalue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6.415\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.498\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.915\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.601\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.834\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\u003eNote: \u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 compared to Group N; \u003csup\u003eb\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 compared to Group S1; \u003csup\u003ec\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 compared to Group S2.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eComparison of VAS and Ramsay scores among groups\u003c/h2\u003e\u003cp\u003eStatistically significant differences in VAS and Ramsay sedation scores were observed across all groups at 2 h, 4 h, 8 h, and 12 h postoperatively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Groups S3, S2, and S1 displayed lower VAS scores than Group N at each postoperative time point. Furthermore, Group S1 at 4 h and 8 h, and Groups S2 and S3 at 4 h, 8 h, and 12 h postoperatively, exhibited higher Ramsay sedation scores in comparison to Group N (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Additionally, Group S3 had significantly higher Ramsay scores than Group S2, which, in turn, showed higher scores than Group S1 at 4 h, 8 h, and 12 h postoperatively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). These findings are denoted in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of VAS and Ramsay scores among groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eTime point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eVAS score\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRamsay sedation score\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eGroup N (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.83\u0026thinsp;\u0026plusmn;\u0026thinsp;0.38\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.97\u0026thinsp;\u0026plusmn;\u0026thinsp;1.16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.23\u0026thinsp;\u0026plusmn;\u0026thinsp;1.52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.63\u0026thinsp;\u0026plusmn;\u0026thinsp;1.33\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.02\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eGroup S1 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.03\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.60\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.67\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.27\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.43\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.48\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eGroup S2 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.07\u0026thinsp;\u0026plusmn;\u0026thinsp;0.32\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.51\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.83\u003csub\u003eab\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.46\u003csub\u003eab\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003csub\u003eab\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"3\" rowspan=\"4\"\u003e\u003cp\u003eGroup S3 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.37\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.34\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.47\u0026thinsp;\u0026plusmn;\u0026thinsp;0.57\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3.17\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003csub\u003eabc\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.00\u0026thinsp;\u0026plusmn;\u0026thinsp;1.02\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.77\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47\u003csub\u003eabc\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31\u003csub\u003ea\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.63\u0026thinsp;\u0026plusmn;\u0026thinsp;0.50\u003csub\u003eabc\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInter-group \u003cem\u003et/P-\u003c/em\u003evalues at 2 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e41.760/\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.225/0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInter-group \u003cem\u003et/P-\u003c/em\u003evalues at 4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26.418/\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.021/\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInter-group \u003cem\u003et/P-\u003c/em\u003evalues at 8 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.071/\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11.888/\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInter-group \u003cem\u003et/P-\u003c/em\u003evalues at 12 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e81.429/\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.259/\u0026lt;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\u003eNote: \u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 compared to Group N; \u003csup\u003eb\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 compared to Group S1; \u003csup\u003ec\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05 compared to Group S2.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eComparison of oxidative stress indicators among groups\u003c/h2\u003e\u003cp\u003eThe inter-group comparison revealed no statistically significant differences in preoperative SOD, MDA, GLU, and COR levels across all groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). At 4 h postoperatively, GLU, COR, and MDA levels were elevated, while SOD levels declined in all groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Furthermore, at 4 h postoperatively, Groups S3, S2, and S1 showed higher SOD levels and lower MDA, GLU, and COR levels in comparison to Group N (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, no statistically significant differences in SOD, MDA, GLU, and COR levels were observed among Groups S3, S2, and S1 at 4 h postoperatively (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). These findings are denoted in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of stress responses among groups (\u003cspan class=\"InlineEquation\"\u003e\u003c/span\u003e)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroups\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eIndicators\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eSOD (U/mL)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eMDA (nmol/L)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eGLU (mmol/L)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eCOR (mmol/L)\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\u003eGroup N (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePreoperative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88.09\u0026thinsp;\u0026plusmn;\u0026thinsp;6.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.24\u0026thinsp;\u0026plusmn;\u0026thinsp;1.29\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e426.63\u0026thinsp;\u0026plusmn;\u0026thinsp;79.96\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60.72\u0026thinsp;\u0026plusmn;\u0026thinsp;9.36\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.31\u0026thinsp;\u0026plusmn;\u0026thinsp;0.77\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.95\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e535.13\u0026thinsp;\u0026plusmn;\u0026thinsp;95.47\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eGroup S1 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePreoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88.68\u0026thinsp;\u0026plusmn;\u0026thinsp;6.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.39\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.58\u0026thinsp;\u0026plusmn;\u0026thinsp;1.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e426.64\u0026thinsp;\u0026plusmn;\u0026thinsp;80.84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68\u0026thinsp;\u0026plusmn;\u0026thinsp;10.33\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.19\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e476.89\u0026thinsp;\u0026plusmn;\u0026thinsp;87.55\u003csup\u003ea\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\u003eGroup S2 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePreoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88.71\u0026thinsp;\u0026plusmn;\u0026thinsp;6.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.53\u0026thinsp;\u0026plusmn;\u0026thinsp;1.40\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.6\u0026thinsp;\u0026plusmn;\u0026thinsp;1.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e426.67\u0026thinsp;\u0026plusmn;\u0026thinsp;80.83\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68.03\u0026thinsp;\u0026plusmn;\u0026thinsp;10.36\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.15\u0026thinsp;\u0026plusmn;\u0026thinsp;0.56\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.25\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e476.9\u0026thinsp;\u0026plusmn;\u0026thinsp;87.54\u003csup\u003ea\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\u003eGroup S3 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePreoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e88.79\u0026thinsp;\u0026plusmn;\u0026thinsp;6.68\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5.59\u0026thinsp;\u0026plusmn;\u0026thinsp;1.47\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e426.73\u0026thinsp;\u0026plusmn;\u0026thinsp;80.91\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68.09\u0026thinsp;\u0026plusmn;\u0026thinsp;10.41\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.16\u0026thinsp;\u0026plusmn;\u0026thinsp;0.62\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.26\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e477\u0026thinsp;\u0026plusmn;\u0026thinsp;87.62\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eInter-group \u003cem\u003et/P\u003c/em\u003e-values preoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.070/0.976\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.386/0.763\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.040/0.989\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.000/1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eInter-group \u003cem\u003et/P\u003c/em\u003e-values at 4 h postoperatively\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.921/0.010\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e83.035/\u0026lt;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.795/0.043\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.164/0.027\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\u003eNote: Compared to Group N, \u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eComparison of adverse events among groups\u003c/h2\u003e\u003cp\u003eThe incidence rates of agitation, nausea, vomiting, drowsiness, respiratory depression, and overall adverse reactions at 12 h postoperatively did not reveal any statistically significant differences between the groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05). However, Group S3 demonstrated significantly higher rates of psychiatric symptoms and hypotension when compared to the other groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). These findings are outlined in 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\u003eComparison of adverse events at 12 h postoperatively among groups\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"8\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"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=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAgitation\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNausea and vomiting\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eDrowsiness\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eRespiratory depression\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDissociation/nightmares and other psychiatric symptoms\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eHypotension\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eTotal incidence\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup N (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3 (10.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (20.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (16.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (6.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e0 (0.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e16 (53.33)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup S1 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (10.00)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2 (6.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2 (6.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e10 (33.33)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup S2 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2 (6.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4 (13.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1 (3.33)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e12 (40.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGroup S3 (30)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2 (6.67)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1 (3.33)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6 (20.00)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e4 (13.33)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e15 (50.00)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u0026minus;\u003c/em\u003e\u003c/sup\u003evalue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e3.050\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cem\u003eP-\u003c/em\u003evalue\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e\u003cp\u003e\u003cb\u003e-\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003e0.384\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\u003eNote: Compared to Group N, \u003csup\u003ea\u003c/sup\u003e\u003cem\u003eP\u003c/em\u003e \u0026lt; 0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eLumbar decompression surgery is a widely performed spinal procedure used to address lumbar spine disorders by alleviating nerve root compression, reducing pain, and enhancing functionality. This surgical intervention is frequently associated with considerable postoperative discomfort, including pain and soreness, necessitating effective anesthesia management for optimal recovery \u003csup\u003e[9\u0026ndash;11]\u003c/sup\u003e. Clinical evidence indicates that the quality of anesthesia achieved with conventional general anesthesia in lumbar decompression surgery is often insufficient. This insufficiency may be explained by individual variability in response to anesthetic agents, which can arise from differences in factors such as physical constitution, age, and preexisting medical conditions. As a result, standard anesthetic dosing may fail to meet the requirements of all patients, leading to suboptimal recovery outcomes for certain individuals.\u003c/p\u003e\u003cp\u003eEsketamine, an intravenous anesthetic, possesses both sedative and analgesic properties. Its unique dextrorotatory configuration enhances its potency, with its primary analgesic action mediated via N-methyl-D-aspartate receptors. This mechanism allows esketamine to provide effective pain relief while exerting minimal respiratory suppression, helping to stabilize postoperative respiratory function. A 2023 study found that low-dose esketamine in thoracoscopic surgery resulted in superior analgesic and anti-inflammatory effects, promoting more efficient patient recovery \u003csup\u003e[12]\u003c/sup\u003e. The findings of this study demonstrate that varying doses of esketamine, when combined with sufentanil, significantly enhanced the quality of anesthesia recovery following general anesthesia. Groups S3, S2, and S1 had reduced sufentanil consumption and fewer effective and total press attempts compared to Group N (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Furthermore, postoperative VAS scores were lower in Groups S3, S2, and S1 than in Group N (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05), with the sub-anesthetic dose of esketamine yielding the most favorable results. This can be attributed to several factors: the synergistic interaction between esketamine and sufentanil plays a crucial role in improving anesthesia quality. Esketamine, when used alongside sufentanil\u0026mdash;a potent opioid analgesic\u0026mdash;produces a synergistic effect, enhancing pain relief while reducing the dosage and adverse effects of both drugs. This interaction provides better pain control during surgery, thereby improving patient comfort and satisfaction \u003csup\u003e[13]\u003c/sup\u003e. The sub-anesthetic dose of esketamine likely achieves an optimal balance, fully utilizing its pharmacological properties and synergizing effectively with sufentanil, while minimizing the side effects and risks associated with higher doses. The superiority of 0.25 mg/kg esketamine may stem from its unique NMDA receptor modulation. At this dose, approximately 60\u0026ndash;70% receptor occupancy (Nikayin et al, 2022) sufficiently blocks pain sensitization while avoiding complete saturation-induced psychotomimetic effects \u003csup\u003e[15]\u003c/sup\u003e. This \"partial inhibition\" simultaneously reduces central sensitization via spinal cord dorsal horn NMDA receptors and preserves synaptic plasticity for cognitive recovery.Our findings align with Qiu et al (JAMA Netw Open 2022) in gynecologic laparoscopy where 0.25 mg/kg showed optimal balance \u003csup\u003e[5]\u003c/sup\u003e. Notably, both studies observed significantly lower COR levels in this dose group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), suggesting sub-anesthetic doses may protect through moderate HPA-axis modulation rather than complete suppression.\u003c/p\u003e\u003cp\u003eThe study did not find statistically significant differences in the incidence of emergence agitation, nausea, vomiting, drowsiness, respiratory depression, or total adverse events among the groups. However, Group S3 exhibited notably higher rates of hypotension and dissociation compared to Group S1. Ramsay sedation scores were also higher in Group S3 compared to Groups S2 and S1 (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). This is likely because higher esketamine doses can cause more pronounced vasodilation, thereby reducing blood pressure \u003csup\u003e[18]\u003c/sup\u003e. Such side effects may compromise postoperative patient safety, and higher doses of esketamine may also increase the likelihood of dissociative symptoms, prolonging recovery time \u003csup\u003e[19]\u003c/sup\u003e. The precise mechanism behind these dissociative symptoms is still unclear, although it may be related to hypotheses involving glutamate and dopamine release \u003csup\u003e[20]\u003c/sup\u003e. Therefore, a sub-anesthetic dose may be optimal for achieving analgesic efficacy while minimizing associated side effects and risks. Esketamine\u0026rsquo;s pharmacological characteristics also contribute significantly to enhancing anesthesia quality. Compared to conventional ketamine, esketamine has fewer side effects and better recovery outcomes \u003csup\u003e[14]\u003c/sup\u003e. It reaches peak plasma levels rapidly and is swiftly metabolized and cleared from the body, shortening anesthesia recovery time and reducing postoperative complications. The results of the study revealed that 4 h postoperatively, all three esketamine groups had higher SOD levels and lower MDA, GLU, and COR levels compared to Group N (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). This suggests that esketamine may also exert neuroprotective effects, potentially limiting neural damage and inflammatory responses during surgery, which in turn improves postoperative recovery quality. The current study did not evaluate depressive symptoms directly, it references Wang et al.'s (2024) evidence supporting the sustained positive effects of low-dose esketamine (0.2 mg/kg) on mood regulation. Notably, the S1 group (presumably the 0.25 mg/kg cohort) exhibited the lowest rate of psychiatric adverse events (6.67%), implying that 0.25 mg/kg might strike an optimal balance between pain management and minimizing neuropsychiatric risks (e.g., hallucinations, agitation). This proposes 0.25 mg/kg as a potential \"therapeutic sweet spot\" for clinical application, underscoring the criticality of dose precision in esketamine therapy\u003csup\u003e[20]\u003c/sup\u003e.Moreover, the necessity for individualized anesthesia management is a crucial factor in selecting the appropriate sub-anesthetic dose of esketamine. Different patients exhibit varying responses to anesthetic agents, requiring adjustments in dosage and administration based on individual needs. In this study, the sub-anesthetic dose of esketamine effectively addressed the needs of most patients, providing adequate analgesia and sedation while avoiding complications associated with higher doses, which is in line with findings from other studies \u003csup\u003e[16]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ethe use of esketamine as an analgesic in lumbar decompression surgery has demonstrated efficacy in reducing the required dosage of sufentanil, mitigating inflammatory responses, and enhancing the overall quality of postoperative recovery. However, the incidence of adverse effects, including hypotension and psychiatric symptoms, was notably higher in the sub-dose group compared to the high-dose group, which necessitates further investigation. Nevertheless, this study has certain limitations. For example, additional clinical parameters such as mood were not evaluated, and the long-term postoperative outcomes were not monitored. These factors will be considered in subsequent research.\u003c/p\u003e\u003c/div\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cstrong\u003ePCA:\u003c/strong\u003epatient-controlled analgesia\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eVAS:\u003c/strong\u003eVisual analogue scale\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSOD:\u003c/strong\u003eSuperoxide dismutase\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMDA:\u003c/strong\u003emalondialdehyde\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eGLU:\u003c/strong\u003eBlood glucose\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCOR:\u003c/strong\u003ecortisol\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis trial was performed in accordance with the Declaration of Helsinki and the Chinese Clinical Trial Specifications.This study was a randomized and controlled trial, which was approved by the\u0026nbsp;Second People\u0026rsquo;s Hospital of Hefei\u0026nbsp;Ethics Committee (PKUSSIRB-202486041, 12 November 2024) and registered with the Chinese Clinical Trial Registry (ChiCTR2500095890, 15 January 2025).\u0026nbsp;All participants were provided with detailed information about the study\u0026apos;s purpose, procedures, potential risks, and benefits prior to their participation. Written informed consent was obtained from each participant, and they were informed of their right to withdraw from the study at any time without any negative consequences.Confidentiality and anonymity of all participants were strictly maintained throughout the study. Data collected were used solely for research purposes and were stored securely in accordance with data protection regulations.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe anesthesia records and patient outcomes analyzed in this study are not publicly deposited to protect participant privacy under the ethical guidelines of Hefei Second People\u0026apos;s Hospital (PKUSSIRB-202486041). Qualified researchers may request access to de-identified data by contacting the corresponding author([email protected])or the Hospital Ethics Committee . A completed data use agreement and research proposal will be required.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests, financial or otherwise, related to this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by the Clinical Medicine Discipline Construction Project of The Second Affiliated Hospital of Anhui Medical University (Grant No. 2023-9101059801). The funder had no role in study design, data collection, analysis, or manuscript preparation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eJunjie Liu conceived and designed the study, performed the experiments, analyzed the data, and wrote the manuscript. Xin Wang contributed to data analysis and interpretation. Panpan Ding assisted with experiments and data collection. Hongjian Wang provided technical support and critical revisions. Xianwen Hu supervised the project, reviewed the manuscript, and provided funding acquisition. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;Acknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors acknowledge funding from the Clinical Medicine Discipline Construction Project (No. 2023-9101059801) at The Second Affiliated Hospital of Anhui Medical University. We extend our gratitude to the orthopedic surgeons for case screening, and to the anesthesiology nursing team for intraoperative monitoring support.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKrauss P, Motov S, Bonk MN, et al.sPinal coRd stimulatiOn coMpared with lumbar InStrumEntation for low back pain after previous lumbar decompression (PROMISE): a prospective multicentre RCT[J].BMJ Open, 2023, 13(4):e067784.\u003c/li\u003e\n\u003cli\u003eHan X, Xu D, Ren Z, et al.Lumbar spinal stenosis combined with obesity-induced idiopathic spinal epidural lipomatosis treated with posterior lumbar fusion: case report [J].BMC Surg , 2021, 21(1):215.\u003c/li\u003e\n\u003cli\u003eBovonratwet P, Samuel AM, Mok JK, et al.Minimally Invasive Lumbar Decompression Versus Minimally Invasive Transforaminal Lumbar Interbody Fusion for Treatment of Low-Grade Lumbar Degenerative Spondylolisthesis [J].Spine (Phila Pa 1976), 2022, 47(21):1505-1514.\u003c/li\u003e\n\u003cli\u003eMorse KW, Steinhaus M, Bovonratwet P, et al .Current treatment and decision-making factors leading to fusion vs decompression for one-level degenerative spondylolisthesis: survey results from members of the Lumbar Spine Research Society and Society of Minimally Invasive Spine Surgery [J].Spine J , 2022, 22(11):1778-1787.\u003c/li\u003e\n\u003cli\u003eQiu D, Wang XM, Yang JJ, et al .Effect of Intraoperative Esketamine Infusion on Postoperative Sleep Disturbance After Gynecological Laparoscopy: A Randomized Clinical Trial [J].JAMA Netw Open , 2022, 5(12):e2244514.\u003c/li\u003e\n\u003cli\u003eZhang Ruiquan, Liang Chao, Chen Zutao. The effect of EEG double-frequency index for monitoring the depth of anesthesia in lower extremity fracture surgery in the elderly [J]. Shenzhen Journal of Integrated Traditional Chinese and Western Medicine, 2022,32 (13): 56-58.\u003c/li\u003e\n\u003cli\u003eWang Dong, Tang Jing, Mo Shan, and so on. To evaluate the value of general anesthesia muscle block during elderly gynecological tumor patients in the perioperative period based on visual analog scoring method and immune function index [J]. China Medical Journal, 2023,58 (4): 417-421.\u003c/li\u003e\n\u003cli\u003eFeng Xiaolu, Cai Yue, Zhao Li, et al. Effect of different administration methods of dexmedetomidine on cognitive function and Ramsay sedation score in elderly patients with radical gastrectomy [J]. Oncology Research and Clinical, 2021,33 (5): 339-343.\u003c/li\u003e\n\u003cli\u003eSuzuki A, Nakamura H.Microendoscopic Lumbar Posterior Decompression Surgery for Lumbar Spinal Stenosis: Literature Review[J].Medicina (Kaunas).2022,58(3):384.\u003c/li\u003e\n\u003cli\u003eZhang F, Zhang W, Zhang R, et al .Modified minimally invasive-transforaminal lumbar interbody fusion under microscopic view to achieve bilateral decompression and fusion through a single approach to treat developmental lumbar spinal stenosis [J].J Clin Neurosci , 2021, 84:46-49.\u003c/li\u003e\n\u003cli\u003eLi P, Tong Y, Chen Y, et al .Comparison of percutaneous transforaminal endoscopic decompression and short-segment fusion in the treatment of elderly degenerative lumbar scoliosis with spinal stenosis [J].BMC Musculoskelet Disord , 2021, 22(1):906.\u003c/li\u003e\n\u003cli\u003eGao quiet, money to the east, Zhou seagull. Effect of low-dose esketamine on postoperative analgesia and inflammatory factors in thoracoscopic patients [J]. Pharmacy in China, 2023,34 (06): 719-723.\u003c/li\u003e\n\u003cli\u003eLi Yijing, Zeng Jilan, You Xiaoying, et al. Effect of HFHD treatment on clinical efficacy and IL-6 and SOD levels in patients with diabetic nephropathy [J]. Journal of Molecular Diagnostics and Therapy, 2022,14 (3): 409-412,417.\u003c/li\u003e\n\u003cli\u003eCordeiro L, Ishikawa WY, Andreoli MCC, et al .A randomized clinical trial to evaluate the effects of icodextrin on left ventricular mass index in peritoneal dialysis [J].Sci Rep , 2022 , 12(1):15776.\u003c/li\u003e\n\u003cli\u003eNikayin S, Murphy E, Krystal JH, et al.Long-term safety of ketamine and esketamine in treatment of depression[J].Expert Opin Drug Saf.2022,21(6):777-787.\u003c/li\u003e\n\u003cli\u003eYoung Kuchenbecker S, Pressman SD, Celniker J, et al .Oxytocin, cortisol, and cognitive control during acute and naturalistic stress [J].Stress , 2021, 24(4):370-383.\u003c/li\u003e\n\u003cli\u003eYe Zhixiang, Shi Yuncen, Huang Ning, et al. The effect of esketamine on intubation on the incidence of post-induction hypotension in patients without muscle relaxation following thyroidectomy: a randomized controlled study [J]. Clinical Medicine in China, 2023,30 (4): 591-598.\u003c/li\u003e\n\u003cli\u003eSun Xiaoxia, Zhang Suqin, Shen Bei, and so on. Role of subanesthetic dose of esketamine in the prevention of hypotension after general anesthesia after gynecological laparoscopy [J]. Zhejiang Medical, 2023,45 (23): 2535-2538,2544.\u003c/li\u003e\n\u003cli\u003eSDuan WY,Peng K, Qin HM, Li BM, Xu YX, Wang DJ, Yu L, Wang H, Hu J, Wang QX.Esketamine accelerates emergence from isoflurane general anaesthesia by activating the paraventricular thalamus glutamatergic neurones in mice.Br J Anaesth.2024 Feb;132(2):334-342.\u003c/li\u003e\n\u003cli\u003eWang DX, et al. Efficacy of a single low dose of esketamine after childbirth for mothers with prenatal depression: randomised clinical trial. BMJ. 2024;385:e078218.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Lumbar decompression surgery, Esketamine, Dose-response relationship, Postoperative analgesia, Oxidative stress, Adverse drug reactions, Randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-6957094/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6957094/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: The optimal esketamine dose for opioid-sparing analgesia in lumbar decompression surgery remains controversial, particularly regarding its dose-dependent effects on recovery quality and safety.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: In this single-center, parallel-group, assessor-blinded randomized controlled trial, 120 patients were allocated via computer-generated randomization (1:1:1:1) to four groups:Group N: Sufentanil2.5µg/kg (control);Groups S1–S3: Esketamine 0.25/0.5/1.0 mg/kg + sufentanil 1.5µg/kg.Primary outcomes included postoperative analgesic consumption, rescue analgesia requirements, and 12-hour VAS scores. Secondary outcomes comprised stress markers and adverse events.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e: No significant differences were observed in rescue analgesia frequency among groups (P \u0026gt; 0.05). However, Group S1 (0.25 mg/kg esketamine) demonstrated significantly lower VAS scores versus Group N (mean difference − 1.8, 95% CI − 2.1 to − 1.5; P \u0026lt; 0.001) and a lower incidence of psychiatric symptoms than Group S3 (6.67% vs. 20.0%; RR 0.33, P = 0.032). Stress markers showed no dose-dependent trends (P \u0026gt; 0.05). While overall adverse event rates were comparable (P \u0026gt; 0.05), high-dose esketamine (S3) was associated with increased hypotension and dissociative symptoms (P \u0026lt; 0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e: Esketamine 0.25 mg/kg effectively reduces sufentanil consumption, prolongs analgesia, and achieves an optimal balance between efficacy and safety in lumbar decompression surgery.\u003c/p\u003e\n\u003cp\u003eTrial registration: ChiCTR-2500095890, 15 January 2025.\u003c/p\u003e","manuscriptTitle":"Effects of Different Doses of Esketamine on Postoperative Analgesia and Recovery Quality in Lumbar Decompression Surgery: A Randomized Controlled Trial Focusing on the Advantages of Sub-Anesthetic Doses","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-01 10:48:03","doi":"10.21203/rs.3.rs-6957094/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0f67cc7d-44bb-4575-acc5-ad869f1a4809","owner":[],"postedDate":"August 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-11T06:08:47+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-01 10:48:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6957094","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6957094","identity":"rs-6957094","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}