Effect of intraoperative dexmedetomidine on early postoperative quality of recovery in patients undergoing endoscopic transsphenoidal surgery for non-functioning pituitary adenoma: a randomized controlled trial

Effect of intraoperative dexmedetomidine on early postoperative quality of recovery in patients undergoing endoscopic transsphenoidal surgery for non-functioning pituitary adenoma: a randomized controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of intraoperative dexmedetomidine on early postoperative quality of recovery in patients undergoing endoscopic transsphenoidal surgery for non-functioning pituitary adenoma: a randomized controlled trial Seungeun Choi, Han Byeol Lim, Kyong Won Shin, Hyongmin Oh, Yong Hwy Kim, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4149671/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 Purpose Intraoperative dexmedetomidine administration attenuates surgical stress response and reduces postoperative pain, which are both essential for enhancing postoperative quality of recovery (QoR). This study aimed to determine whether intraoperative dexmedetomidine could improve early postoperative QoR in patients with nonfunctioning pituitary adenoma (NFPA) undergoing endoscopic transsphenoidal surgery (ETS). Methods Patients with NFPA who underwent ETS under total intravenous anesthesia using continuous infusion of propofol and remifentanil were randomly assigned to receive either intraoperative dexmedetomidine (dexmedetomidine group, n = 29) or normal saline (control group, n = 32). The QoR-15 questionnaire was used to evaluate the postoperative QoR. The primary outcome measure was the QoR-15 score on postoperative day 1. Perioperative serum cortisol levels, intraoperative serum interleukin-6 levels, and pain scores at 4, 24, and 48 h postoperatively were also evaluated. Results The QoR-15 score on postoperative day 1 did not differ between the dexmedetomidine and control groups (94.0 [79.0–112.0] vs. 92.5 [68.3–110.8], P = 0.606). Perioperative serum cortisol levels showed no significant time × group effect (P = 0.578). Intraoperative serum interleukin-6 level did not differ between the two groups (P = 0.974). Pain score was lower in the dexmedetomidine group at 4 h postoperatively (0.0 [0.0–0.0] vs. 1.0 [0.0–3.0], P = 0.003) than the control group. Conclusion Dexmedetomidine, as an anesthetic adjuvant, did not improve early postoperative QoR in patients with NFPA during ETS. Dexmedetomidine Nonfunctioning pituitary adenoma Endoscopic transsphenoidal surgery Quality of recovery Figures Figure 1 Introduction Surgical stress response refers to physiological reactions to surgical trauma involving neuroendocrine, immunologic, and metabolic changes [ 1 ]. Surgical stimuli release various stress hormones (e.g., cortisol and catecholamine) and inflammatory cytokines (e.g., tumor necrosis factor alpha and various interleukins) [ 2 , 3 ]. Stress hormones and inflammatory mediators are associated with postoperative infection, delayed wound healing, and multiple organ dysfunction, ultimately resulting in impaired postoperative quality of recovery (QoR) [ 2 , 4 ]. In patients with nonfunctioning pituitary adenoma (NFPA) undergoing endoscopic transsphenoidal surgery (ETS), the surgical stress response may be more intense and complex than in other surgical patients. Surgical manipulation directly damages the pituitary gland, which plays a major role in regulating the endocrine system [ 5 ]. In addition, patients with NFPA are at risk of an impaired hypothalamic-pituitary-adrenal axis as the mass effect caused by NFPA can lead to mechanical pressure on the normal pituitary gland and deviation of the pituitary stalk [ 6 ]. Therefore, it is important to appropriately manage the surgical stress response in patients with NFPA undergoing ETS. Dexmedetomidine, a selective α2-adrenergic agonist, provides sedation and pain relief and inhibits the sympathetic nervous system [ 7 ]. Recently, it has been recognized as a major anesthetic adjuvant in enhanced recovery after surgery (ERAS) programs to decrease postoperative pain [ 8 ]. In addition, a previous meta-analysis demonstrated that intraoperative dexmedetomidine use attenuates perioperative stress responses and inflammatory reactions in various surgical patients [ 9 ]. In neurosurgical patients, dexmedetomidine is widely used because of its ability to reduce perioperative opioid consumption, stabilize intraoperative hemodynamics, and alleviate the surgical stress response [ 10 ]. However, no study has determined whether dexmedetomidine improves the postoperative QoR in patients with NFPA undergoing ETS. This study hypothesized that intraoperative dexmedetomidine administration would improve early postoperative QoR by reducing the surgical stress response and postoperative pain in patients with NFPA undergoing ETS. In this study, the Korean version of the QoR-15 was used to assess the postoperative QoR [ 11 ]. The QoR-15 score on postoperative day 1 was compared between patients who received intraoperative dexmedetomidine and those who did not. In addition, perioperative pituitary hormone levels, including cortisol levels, intraoperative serum interleukin-6 levels, postoperative pain scores, and the incidence of postoperative complications were compared. Methods Ethics This randomized controlled trial was approved by the Institutional Review Board of Seoul National University Hospital (number: H-2106-149-1230, date: July 22, 2021) and registered at ClinicalTrials.gov (NCT number: 05005715, date: August 13, 2021). This study followed the Good Clinical Practice guidelines, and the manuscript was written according to the applicable Consolidated Standard of Reporting Trials guidelines. Written informed consent was obtained from all patients before their participation in the study. Subjects Patients aged 20–65 years with NFPA who were scheduled to undergo ETS under general anesthesia were included in this study. Patients who had a contraindication to dexmedetomidine (known hypersensitivity to dexmedetomidine, uncontrolled hypertension, severe left ventricular dysfunction, and second- or third-degree heart block); a previous history of ETS within a year; coagulopathy; psychiatric disorder; difficulty in completing the QoR-15 questionnaire; myasthenia gravis or myasthenic syndrome; history of hypersensitivity to propofol, remifentanil, and rocuronium; pregnancy; or breastfeeding were excluded. Patients who had undergone preoperative steroid replacement were also excluded. Randomization Group randomization using computer-generated four-sized blocks was performed by an anesthesiologist who was not involved in the study. The patients were randomly assigned to either the dexmedetomidine or control group based on the allocation sequence in a 1:1 ratio. The allocation sequence was contained in sealed envelopes and disclosed before anesthesia induction by a nurse in charge of preparing the study or control drugs in the same volume. As a result, the anesthesiologists, surgeons, and patients were blinded to the randomization. Study protocol Before surgery, the serum levels of pituitary hormones (adrenocorticotropic hormone [ACTH], cortisol, triiodothyronine [T3], thyroxine [T4], thyroid stimulating hormone [TSH], growth hormone [GH], insulin-like growth factor 1 [IGF-1], luteinizing hormone [LH], follicle-stimulating hormone [FSH], and prolactin) were measured, and preoperative QoR was evaluated using the QoR-15 questionnaire. The patients entered the operating room without premedication and were monitored using pulse oximetry, electrocardiography, and noninvasive blood pressure measurements. Anesthesia was induced with continuous infusion of propofol (effect site concentration: 4 µg/mL) and remifentanil (effect site concentration: 4 ng/mL) using a target-controlled device (Orchestra base primea, Fresenius Kabi, Bad Homburg, Germany). After confirming loss of consciousness, rocuronium (0.6–0.8 mg/kg) was administered to facilitate tracheal intubation. Intravenous acetaminophen (1,000 mg) was administered for preemptive analgesia. After tracheal intubation, an arterial catheter was placed in the patient’s radial artery for continuous blood pressure monitoring, and an additional peripheral venous catheter was placed in the patient’s forearm for fluid infusion and drug administration. During anesthetic maintenance, the effect site concentrations of propofol and remifentanil were adjusted to maintain blood pressure within ± 20% of preoperative value and a bispectral index of 30–60. Rocuronium was not administered after tracheal intubation. Mechanical ventilation was controlled to maintain normocapnia. After anesthetic induction, in the dexmedetomidine group, a loading dose of dexmedetomidine at 1 µg/kg was administered intravenously over 10 min, followed by a maintenance dose of dexmedetomidine at 0.5 µg/kg/h continuous infusion until the end of surgery [ 12 ]. In the control group, normal saline was intravenously administered with the same loading volume of dexmedetomidine for 10 min and continuously infused at the same maintenance dose of dexmedetomidine until the end of surgery. When tumor resection began, blood samples were collected to measure intraoperative pituitary hormones (ACTH, cortisol, T3, T4, TSH, GH, IGF-1, LH, FSH, prolactin, and antidiuretic hormones [ADH]) in both groups. Intraoperative serum interleukin-6 (IL-6) levels were simultaneously measured. Intravenous ramosetron (0.3 mg) and fentanyl (100 µg) were administered 30 min before the end of surgery to prevent postoperative nausea and vomiting (PONV) and postoperative pain. After surgery, patients underwent immediate postoperative brain computed tomography (CT) in the operating room. Subsequently, the administration of propofol, remifentanil, and either dexmedetomidine or normal saline was discontinued, and the patients were transferred to the neurointensive care unit without receiving any additional sedatives or neuromuscular blocking agents. After admission to the neurointensive care unit, immediate postoperative pituitary hormone (ACTH, cortisol, T3, T4, TSH, GH, IGF-1, LH, FSH, and prolactin) tests were conducted. Extubation was performed in the neurointensive care unit when the patients were alert and their spontaneous breathing had sufficiently recovered. The times to emergence and extubation were recorded. Postoperative QoR was assessed using the QoR-15 questionnaire on postoperative day 1. Briefly, patients were asked 15 questions to assess five domains of patient-reported health status: physical comfort, physical independence, psychological support, emotional state, and pain. The 11-point numerical rating scale of 15 items has a minimum score of 0 (very poor recovery) and a maximum score of 150 (excellent recovery) [ 11 ]. Postoperative cortisol levels were measured on postoperative days 1, 2, and 3. Intravenous acetaminophen (1,000 mg) and oral acetaminophen (650 mg) were administered every 8 h before and after resuming oral fluids, respectively. If a patient complained of PONV, intravenous ramosetron (0.3 mg) or metoclopramide (10 mg) was administered. Postoperative pain scores were assessed using a numeric rating scale (NRS; 0, no pain; 10, worst pain imaginable) at 4, 24, and 48 h postoperatively. If NRS score of ≥ 4 was noted, a rescue analgesic (acetaminophen [1000 mg], ketorolac [30 mg], or fentanyl [50 µg]) was intravenously administered. The incidence of rescue analgesic administration and PONV was investigated at 4, 24, and 48 h postoperatively. The incidence of postoperative complications, such as diabetes insipidus, hyponatremia, infection, cerebrospinal fluid leakage, hemorrhage, and hydrocephalus, was noted. Postoperative pituitary function outcomes were investigated 3 months postoperatively. Study outcomes The primary outcome measure was the QoR-15 score on postoperative day 1. Secondary outcome measures included preoperative QoR-15 score, perioperative pituitary hormone levels (ACTH, cortisol, T3, T4, TSH, GH, IGF-1, LH, FSH, prolactin, and ADH), intraoperative serum IL-6 levels, postoperative pain scores, incidence of postoperative complications, and pituitary functional outcome at 3 months postoperatively. ACTH deficiency was diagnosed in the following cases: serum cortisol < 18 µg/dL in the insulin-induced hypoglycemia test, peak cortisol < 18 µg/dL in the short ACTH test, morning cortisol < 8 µg/dL, or random cortisol < 5 µg/dL with a low to normal serum ACTH level [ 13 ]. TSH deficiency was defined as free T4 < 0.7 ng/dL with a low to normal TSH level [ 14 ]. GH deficiency was identified when peak GH < 3 ng/mL in the insulin-induced hypoglycemia test; if insulin-induced hypoglycemia test was not conducted, GH deficiency was determined by IGF-1 level below normal range, accompanied by deficiencies in ACTH, TSH, and gonadotropin [ 14 ]. Gonadotropin deficiency in men was defined as testosterone 30 mIU/mL and estradiol < 50 pg/mL in female patients with GN deficiency [ 14 ]. Sample size calculation In a previous study, postoperative QoR-15 score on postoperative day 1 was 134.3 ± 17.3 in patients who underwent elective craniotomy [ 15 ]. Assuming that postoperative QoR-15 score increases by 10% when dexmedetomidine is administered, a minimum sample size of 27 patients was needed in each group when setting the α and β to 0.05 and 0.2, respectively. Considering a drop rate of 15%, 64 patients were required. Statistical analysis Statistical analyses were conducted using the SPSS software (version 25, IBM Corp., Armonk, NY, USA). Categorical variables were presented as the number of patients (proportion), and continuous variables were presented as mean (standard deviation) or median (interquartile range). Pearson’s chi-square test or Fisher’s exact test was used to compare categorical variables based on the expected cell counts. For continuous variables, the Shapiro–Wilk test was first used to assess the normality of data distribution, and the Student’s t-test and Mann–Whitney U-test were used to compare normally distributed and skewed data, respectively. The time × group effects of perioperative pituitary hormone levels and postoperative pain scores were evaluated using repeated-measures analysis of variance. If a significant time × group effect was observed, Bonferroni correction with compensating for multiple comparisons was applied to compare the variables between the two groups at each time point: an alpha of 0.008 (0.05/6) was applied for perioperative serum cortisol levels, and 0.017 (0.05/3) was applied for perioperative serum levels of other pituitary hormones (ACTH, T3, T4, TSH, GH, IGF-1, LH, FSH, and prolactin) and postoperative pain scores. For other variables, p value < 0.05 was considered statistically significant. Results In total, 64 patients were enrolled between August 2021 and April 2023 (Fig. 1 ). Among these patients, three (one withdrawal of consent and two preoperative steroid administrations) were excluded from the dexmedetomidine group. Finally, 29 patients in the dexmedetomidine group and 32 patients in the control group were included in the analysis. There were no significant differences in demographics, preoperative pituitary hormone levels, tumor characteristics, or the extent of surgical resection between the dexmedetomidine and control groups (Table 1 ). Intraoperative mean blood pressure (87.2 (81.3–94.0) vs. 78.9 (75.9–85.3) mmHg, P < 0.001) was higher and the value of bispectral index (35.0 (31.5–40.7) vs. 41.3 (36.7–45.7), P = 0.002) was lower in the dexmedetomidine group than the control group. Table 1 Comparison of demographic and intraoperative variables between the dexmedetomidine and control groups Variables Dexmedetomidine group (n = 29) Control group (n = 32) P value Age (yr) 51.0 (40.5–59.0) 50.0 (42.0–57.0) 0.971 Male sex 13 (44.8%) 17 (53.1%) 0.696 Height (cm) 164.4 (156.6–172.3) 164.2 (159.3–170.9) 0.778 Weight (kg) 65.5 (58.5–77.5) 68.0 (57.6–76.8) 0.868 Body mass index (kg/m 2 ) 25.1 (23.0–27.5) 25.0 (22.1–28.3) 0.806 ASA PS class 0.541 I 14 (48.3%) 19 (59.4%) II 15 (51.7%) 13 (40.6%) Preoperative serum level of pituitary hormones Cortisol (µg/dL) 9.4 (4.8–12.7) 10.3 (5.7–15.0) 0.222 ACTH (pg/mL) 26.8 (17.9–43.3) 23.8 (16.1–45.6) 0.929 T3 (ng/dL) 121.0 (102.5–130.0) 120.5 (102.5–139.5) 0.670 T4 (ng/dL) 1.06 (0.96–1.19) 1.04 (0.93–1.14) 0.418 TSH (µIU/mL) 1.50 (0.96–2.36) 1.43 (1.01–2.78) 0.544 LH (mIU/mL) 2.2 (1.4–3.8) 2.0 (1.5–3.4) 0.925 FSH (mIU/mL) 5.6 (3.2–8.9) 5.5 (3.5–7.1) 0.874 IGF-1 (ng/mL) 109.0 (62.0–149.0) 91.0 (70.5–131.5) 0.745 GH (ng/mL) 0.30 (0.09–0.46) 0.21 (0.08–0.50) 0.732 Prolactin (ng/mL) 14.5 (5.9–46.0) 18.5 (6.7–36.2) 0.806 Preoperative pituitary hormone deficiency ACTH 2 (6.9%) 2 (6.3%) 1.000 TSH 1 (3.4%) 1 (3.1%) 1.000 GH 4 (13.8%) 2 (6.3%) 0.411 Gonadotropin 5 (17.2%) 5 (15.6%) 1.000 Tumor characteristics Tumor volume (cm 3 ) 4.78 (3.25–7.45) 5.62 (3.06–7.76) 0.697 Optic chiasm compression 22 (75.9%) 25 (78.1%) 1.000 Cavernous sinus invasion 5 (17.2%) 6 (18.8%) 1.000 Surgery Degree of resection 0.338 Grossly total resection 26 (89.7%) 31 (96.9%) Subtotal resection 3 (10.3%) 1 (3.1%) Intraoperative CSF leakage 5 (17.2%) 6 (18.8%) 1.000 Anesthesia Anesthetic time (min) 125.0 (105.0–142.5) 120.0 (111.3–145.0) 0.891 Intraoperative vital signs Heart rate (beats/min) 63.3 (57.2–69.3) 61.7 (57.2–68.9) 0.751 Mean blood pressure (mmHg) 87.2 (81.3–94.0) 78.9 (75.9–85.3) < 0.001 Body temperature (℃) 36.1 (35.8–36.2) 36.0 (35.6–36.3) 0.466 Bispectral index 35.0 (31.5–40.7) 41.3 (36.7–45.7) 0.002 Infusion rate Propofol (mg/kg/min) 0.15 (0.13–0.17) 0.15 (0.13–0.18) 0.479 Remifentanil (µg/kg/min) 0.15 (0.12–0.18) 0.15 (0.14–0.18) 0.806 ASA PS, American Society of Anesthesiologists physical status; ACTH, adrenocorticotropic hormone; TSH: thyroid stimulating hormone; GH: growth hormone; CSF, cerebrospinal fluid There was no significant difference in the QoR-15 score on postoperative day 1 between the dexmedetomidine and control groups (94.0 [78.0–114.0] vs. 92.5 [68.3–110.8], P = 0.598) (Table 2 ). Table 2 Comparison of perioperative Quality of Recovery-15 scores between the dexmedetomidine and control groups Variables Dexmedetomidine group (n = 29) Control group (n = 32) Median difference (95% CI) P value QoR-15 score Preoperative day 141.0 (125.5–148.0) 141.0 (129.3–147.0) 0.0 (-6.0–6.0) 0.816 Physical comfort 48.0 (43.0–50.0) 50.0 (44.0–50.0) 0.0 (-3.0–0.0) 0.330 Physical independence 20.0 (20.0–20.0) 20.0 (20.0–20.0) 0.0 (0.0–0.0) 0.770 Psychological support 20.0 (20.0–20.0) 20.0 (20.0–20.0) 0.0 (0.0–0.0) 0.192 Emotions 36.0 (30.0–38.5) 36.0 (27.0–39.5) 0.0 (-2.0-3.0) 0.827 Pain 20.0 (15.5–20.0) 20.0 (19.0–20.0) 0.0 (0.0–0.0) 0.329 Postoperative day 1 94.0 (78.0–114.0) 92.5 (68.3–110.8) 3.0 (-11.0–18.0) 0.598 Physical comfort 28.0 (16.0–39.0) 33.5 (25.5–40.8) -6.0 (-13.0–0.0) 0.088 Physical independence 10.0 (3.5–14.5) 7.0 (2.0–15.0) 0.0 (-3.0–4.0) 0.805 Psychological support 19.0 (15.0–20.0) 17.0 (13.0–20.0) 0.0 (0.0–3.0) 0.249 Emotions 30.0 (23.5–36.5) 27.0 (19.0–34.8) 3.0 (-2.0–8.0) 0.275 Pain 13.0 (8.0–15.5) 11.0 (8.3–15.0) 1.0 (-2.0–3.0) 0.602 QoR, Quality of Recovery; CI, confidence interval. Perioperative serum cortisol levels (preoperative, intraoperative, immediate postoperative, and on postoperative days 1, 2, and 3) showed no significant time × group effects (P = 0.578). In addition, other perioperative pituitary hormone levels (preoperative, intraoperative, and immediately postoperative) showed no significant time × group effects. Intraoperative serum IL-6 levels did not differ significantly between the two groups (Table 3 ). Table 3 Comparison of intraoperative and postoperative pituitary hormone and intraoperative interleukin-6 levels between the dexmedetomidine and control groups Variables Dexmedetomidine group (n = 29) Control group (n = 32) Median difference (95% CI) P value Intraoperative Cortisol (µg/dL) 7.5 (18.5–4.5) 10.1 (4.7–15.1) -1.0 (-4.4–2.9) 0.608 ACTH (pg/mL) 22.8 (12.1–44.5) 28.0 (16.9–60.7) -4.9 (-15.2–5.3) 0.323 T3 (ng/dL) 99.0 (89.5–106.0) 97.5 (88.0–110.8) -3.0 (-11.0–5.0) 0.492 T4 (ng/dL) 1.13 (1.03–1.21) 1.14 (1.02–1.26) -0.01 (-0.09–0.08) 0.800 TSH (µIU/mL) 1.17 (0.67–2.27) 1.32 (0.85–2.50) -0.25 (-0.76–0.20) 0.263 LH (mIU/mL) 1.8 (1.2–3.0) 2.0 (1.2–2.6) 0.1 (-0.6–0.6) 0.795 FSH (mIU/mL) 5.5 (3.3–8.0) 4.3 (3.0–6.1) 0.8 (-1.0–2.4) 0.457 IGF-1 (ng/mL) 83.0 (51.0–121.5) 86.5 (63.5–130.0) -6.0 (-30.0–19.0) 0.686 GH (ng/mL) 0.84 (0.19–2.09) 0.27 (0.09–0.44) 0.33 (0.02–0.92) 0.026 Prolactin (ng/mL) 28.2 (9.5–50.5) 28.7 (12.0–53.8) -2.7 (-14.6–7.9) 0.583 ADH (pmol/L) a 1.7 (0.8–4.1) 1.0 (0.8–6.1) 0.0 (-0.2–0.8) 0.586 Interleukin-6 (pg/mL) b 1.78 (1.50–2.50) 1.75 (1.50–2.47) 0.00 (-0.37–0.53) 0.974 Immediate postoperative Cortisol (µg/dL) c 19.1 (24.6–15.0) 19.2 (16.1–23.5) -0.6 (-4.5–2.9) 0.723 ACTH (pg/mL) d 133.3 (42.0–164.6) 133.1 (71.9–220.6) -12.3 (-64.2–41.0) 0.610 T3 (ng/dL) d 95.0 (85.0–112.0) 104.0 (91.5–112.0) -5.0 (-14.0–4.0) 0.322 T4 (ng/dL) d 1.18 (1.00–1.25) 1.12 (1.03–1.24) 0.03 (-0.06–0.01) 0.599 TSH (µIU/mL) d 1.78 (0.96–3.31) 2.69 (1.54–4.27) -0.70 (-1.60–0.11) 0.093 LH (mIU/mL) d 2.6 (1.4–3.3) 2.2 (1.4–3.7) 0.1 (-0.6–0.9) 0.802 FSH (mIU/mL) d 5.9 (3.4–8.1) 4.6 (3.4–6.0) 0.7 (-1.0–2.5) 0.353 IGF-1 (ng/mL) d 77.0 (54.0–116.0) 86.5 (63.3–118.0) -8.5 (-29.0–14.0) 0.451 GH (ng/mL) d 1.46 (0.74–2.89) 1.13 (0.69–2.30) 0.16 (-0.39–0.73) 0.605 Prolactin (ng/mL) d 28.2 (9.5–50.5) 28.7 (12.0–53.8) -2.8 (-12.4–5.9) 0.475 Postoperative day 1 e Cortisol (µg/dL) 21.1 (13.5–28.0) 16.3 (7.8–22.0) 5.6 (0.8–10.8) 0.024 Postoperative day 2 e Cortisol (µg/dL) 12.3 (8.4–15.9) 11.5 (6.4–16.0) 0.3 (-2.7–3.4) 0.756 Postoperative day 3 f Cortisol (µg/dL) 9.4 (5.2–12.7) 9.5 (3.2–12.5) 0.8 (-2.0–4.1) 0.613 a n = 27 in the dexmedetomidine group and n = 31 in the control group. b n = 10 in the dexmedetomidine group and n = 12 in the control group. c n = 29 in the dexmedetomidine group and n = 32 in the control group. d n = 27 in the dexmedetomidine group and n = 32 in the control group. e n = 28 in the dexmedetomidine group and n = 32 in the control group. f n = 28 in the dexmedetomidine group and n = 30 in the control group. ACTH, adrenocorticotropic hormone; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone; GH, growth hormone; IGF-1, insulin-like factor 1; LH, luteinizing hormone; FSH, follicle-stimulating hormone; ADH, antidiuretic hormone; CI, confidence interval. Emergence time (37.0 [24.0–47.0] vs. 21.0 [12.3–32.3] min, P = 0.001) and extubation time (63.0 [40.0–85.0] vs. 36.5 [18.3–53.3] min, P < 0.001) were longer in the dexmedetomidine group than the control group (Table 4 ). The postoperative pain scores showed a significant time × group effect (P = 0.027). The pain score was significantly lower in the dexmedetomidine group only at 4 h postoperatively (0.0 [0.0–0.0] vs 1.0 [0.0–3.0], P = 0.003), while it did not differ at 24 and 48 h postoperatively. The total number of rescue analgesics administered, incidence of PONV and postoperative complications, and pituitary functional outcome at 3 months postoperatively did not differ between the two groups. Table 4 Comparison of postoperative outcomes between the dexmedetomidine and control groups Variables Dexmedetomidine group (n = 29) Control group (n = 32) Proportional or Median difference (95% CI) P value Time to emergence (min) 37.0 (26.5–47.0) 21.0 (12.3–32.3) 14.0 (6.0–22.0) 0.001 Time to extubation (min) 63.0 (39.5–81.0) 36.5 (18.3–53.3) 24.0 (11.0–36.0) < 0.001 Postoperative pain a 4 h postoperatively 0.0 (0.0–0.0) 1.0 (0.0–3.0) -1.0 (-2.0–0.0) 0.003 24 h postoperatively 3.0 (2.0–3.0) 3.0 (2.0–3.0) 0.0 (0.0–0.0) 0.914 48 h postoperatively 3.0 (2.5–3.0) 3.0 (2.0–4.0) 0.0 (-1.0–0.0) 0.602 Total number of rescue analgesics administered 4 h postoperatively 0.0 (0.0–0.0) 0.0 (0.0–1.0) 0.0 (0.0–0.0) 0.134 24 h postoperatively 0.0 (0.0–1.5) 0.5 (0.0–1.0) 0.0 (0.0–0.0) 0.354 48 h postoperatively 1.0 (0.0–1.5) 1.0 (0.0–2.0) 0.0 (-1.0–0.0) 0.727 Postoperative nausea and vomiting 4 h postoperatively 2 (6.9%) 0 (0.0%) 6.9% (-2.9–16.7%) 0.222 24 h postoperatively 1 (3.4%) 3 (9.4%) -5.9% (-18.7–6.9%) 0.614 48 h postoperatively 2 (6.9%) 3 (9.4%) -2.5% (-16.8–11.8%) 1.000 Pituitary hormone deficiency at 3 months postoperatively ACTH 4 (13.8%) 2 (6.3%) 7.5% (-8.2–23.3%) 0.577 TSH 2 (6.9%) 0 (0.0% 6.9% (-2.9–16.7%) 0.222 GH 13 (44.8%) 12 (37.5%) 7.3% (-18.3–32.9%) 0.749 Gonadotropin 11 (37.9%) 11 (34.4%) 3.6% (-21.5–28.6%) 0.983 Postoperative complications Diabetes insipidus 6 (20.7%) 7 (21.9%) -1.2% (-22.5–20.2%) 1.000 Hyponatremia 2 (6.9%) 5 (15.6%) -8.7% (-24.9–7.5%) 0.429 Infection 0 (0.0%) 1 (3.1%) -3.1% (-9.7–3.4%) 1.000 CSF leakage 0 (0.0%) 0 (0.0%) NA NA Hemorrhage 0 (0.0%) 0 (0.0%) NA NA Hydrocephalus 1 (3.4%) 0 (0.0%) 3.4% (-3.6–10.5%) 0.475 a Postoperative pain was assessed using a numeric rating scale (0, no pain; 10, worst pain imaginable). ACTH, adrenocorticotropic hormone; TSH, thyroid-stimulating hormone; GH, growth hormone; CSF, cerebrospinal fluid; CI, confidence interval; NA, not applicable. Discussion Recently, postoperative QoR has become a major concern for both anesthesiologists and surgeons. Various trials have been performed to improve postoperative QoR. This randomized controlled trial explored the impact of intraoperative dexmedetomidine administration on postoperative QoR in patients with NFPA undergoing ETS. This study showed that the intraoperative administration of dexmedetomidine did not improve postoperative QoR in such patients. Reducing the perioperative surgical stress response, one of the targets of the ERAS program [ 16 ], is very important for improving postoperative QoR. Dexmedetomidine has various beneficial effects, such as improving intraoperative hemodynamic stability, decreasing intraoperative norepinephrine release, and reducing the requirement for anesthetics and analgesics, when used as an anesthetic adjuvant in patients undergoing ETS [ 12 , 17 – 19 ]. In this study, we believed that intraoperative dexmedetomidine would improve the postoperative QoR by reducing the surgical stress response. However, dexmedetomidine did not decrease serum levels of stress hormones or increase postoperative QoR-15 scores in this study. There were several reasons for this observation. First, propofol and remifentanil were used as the main anesthetics. Propofol attenuates surgical stress response by inhibiting the release of stress hormones, including cortisol, epinephrine, and norepinephrine, in response to surgical stimuli [ 20 , 21 ]. Remifentanil has also been reported to decrease the serum levels of surgical stress hormones during the perioperative period [ 22 – 24 ]. Such strong anti-stress effects of propofol and remifentanil may result in non-significant differences in the perioperative stress response and postoperative QoR when dexmedetomidine is used as an anesthetic adjuvant. In other words, we believe that the anti-stress effect of dexmedetomidine may be overwhelmed by that of propofol and remifentanil, possibly masking the beneficial effect of dexmedetomidine on the reduced stress response. Indeed, most previous studies have reported that additional intraoperative dexmedetomidine administration could help improve postoperative QoR when combined with inhalation anesthesia, but not when using propofol [ 25 – 30 ]. Second, ETS is a minimally invasive procedure involving a small incision and minimal normal tissue damage, resulting in less surgical stress responses [ 31 ]. Owing to the less invasive nature of ETS, the beneficial effect of dexmedetomidine on stress hormones was not evident. Third, the dexmedetomidine group required more time for extubation, and a prolonged intubated time may have compromised the postoperative QoR. Intubated patients experience various physical and psychological stresses, including discomfort, pain, inability to speak and communicate, anxiety, and fear [ 32 ]. Even within a short period, being intubated and mechanically ventilated in an awake state can result in the deterioration of postoperative QoR. Postoperative pain directly affects the postoperative QoR. In this study, the analgesic effect of dexmedetomidine was statistically significant at 4 h postoperatively; however, the difference was not clinically significant. This can be attributed to the characteristics of the ETS and effective perioperative pain management. This minimally invasive surgical technique for ETS leads to reduced postoperative pain and inflammation [ 31 ]. Infiltration of the nasal mucosa with epinephrine and lidocaine during surgical preparation further reduces postoperative pain [ 31 ]. In addition, preemptive acetaminophen administration, fentanyl administration before the end of surgery, periodic administration of acetaminophen during the postoperative period, and active use of rescue analgesics would be helpful for postoperative pain relief. In other words, the analgesic effect of dexmedetomidine may not have been remarkable because postoperative pain was effectively controlled using a multimodal analgesia protocol. In addition, postoperative QoR can be negatively affected by opioid-related complications. Intraoperative dexmedetomidine potentiates the analgesic effects of opioids, thereby reducing perioperative opioid consumption [ 33 ]. This decrease in opioid use can lead to reduced opioid-related side effects (PONV), contributing to an improved postoperative QoR. However, the study did not reduce intraoperative opioid consumption. This finding may be due to dexmedetomidine-induced hypertension [ 34 ]. Dexmedetomidine caused an increase in blood pressure at the beginning of the infusion, which necessitated the administration of a higher dose of remifentanil in the dexmedetomidine group. However, as the infusion continued, the need for remifentanil decreased, ultimately resulting in a similar overall remifentanil dose. In other words, an opioid-sparing effect was not observed in the dexmedetomidine group, which may partly explain the lack of improvement in postoperative QoR. This study had several limitations. First, this was a single-center study conducted on patients with NFPA who underwent ETS under total intravenous anesthesia. Therefore, these results cannot be generalized to other patients with functional pituitary tumors, those undergoing craniotomy for pituitary tumor removal, and those receiving inhalation anesthesia. Second, dexmedetomidine was administered at a fixed dose to all patients. Therefore, we could not determine whether the anti-stress effects of dexmedetomidine were dose dependent. In addition, only serum cortisol levels, a serum marker of stress response, were investigated in this study. Therefore, we did not know the effect of intraoperative dexmedetomidine on other serum markers of the stress response (i.e., epinephrine and norepinephrine). Third, the postoperative QoR was evaluated only on postoperative day 1. Therefore, we could not determine the time at which the postoperative QoR returned to baseline. Further studies are needed to explore the long-term effects of intraoperative dexmedetomidine on postoperative QoR. In conclusion, dexmedetomidine, as an anesthetic adjuvant, did not improve the postoperative QoR in patients with NFPA who underwent ETS under total intravenous anesthesia during ETS. Further research is warranted to identify ways to improve the postoperative QoR in such patients. Declarations Funding: This study was funded by research grants funded by Seoul National University Hospital (Grant number: 0420210400). Conflict of Interest/Competing interests: The authors have no relevant financial or non-financial interests to disclose. Ethics approval: This study was conducted in accordance with ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Consent to participate: Informed consent was obtained from all patients before participation. Availability of data and material: The data and materials of this study are available upon request to the corresponding author. References Helander, E. M., Webb, M. P., Menard, B., Prabhakar, A., Helmstetter, J., Cornett, E. M., Urman, R. D., Nguyen, V. H., & Kaye, A. D.: Metabolic and the surgical stress response considerations to improve postoperative recovery. Curr. Pain Headache Rep. 23, 33 (2019). https://doi.org/10.1007/s11916-019-0770-4 Kurosawa, S., Kato, M.: Anesthetics, immune cells, and immune responses. J. Anesth. 22, 263–277 (2008). https://doi.org/10.1007/s00540-008-0626-2 Baigrie, R.J., Lamont, P.M., Kwiatkowski, D., Dallman, M.J., Morris, P.J.: Systemic cytokine response after major surgery. Br. J. Surg. 79, 757–760 (1992). https://doi.org/10.1002/bjs.1800790813 Homburger, J.A., Meiler, S.E.: Anesthesia drugs, immunity, and long-term outcome. Curr. Opin. Anaesthesiol. 19, 423–428 (2006). https://doi.org/10.1097/01.aco.0000236143.61593.14 Kaplan, S.A.: The pituitary gland: A brief history. Pituitary 10, 323–325 (2007). https://doi.org/10.1007/s11102-007-0050-x Yhim, H.B., Oh, H.M., Yoon, H.K., Kim, Y.H., Park, H.P.: A retrospective observational study of the neuroendocrine stress response in patients undergoing endoscopic transsphenoidal surgery for removal of pituitary adenomas: Total intravenous versus balanced anesthesia. J. Neurosurg. Anesthesiol. 33, 137–146 (2021). https://doi.org/10.1097/ANA.0000000000000638 Khan, Z.P., Ferguson, C.N., Jones, R.M.: alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 54, 146–165 (1999). https://doi.org/10.1046/j.1365-2044.1999.00659.x Kaye, A. D., Chernobylsky, D. J., Thakur, P., Siddaiah, H., Kaye, R. J., Eng, L. K., Harbell, M. W., Lajaunie, J., Cornett, E. M.: Dexmedetomidine in enhanced recovery after surgery (ERAS) protocols for postoperative pain. Curr. Pain Headache Rep. 24, 21 (2020). https://doi.org/10.1007/s11916-020-00853-z Wang, K., Wu, M., Xu, J., Wu, C., Zhang, B., Wang, G., Ma, D.: Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: Systematic review and meta-analysis. Br. J. Anaesth. 123, 777–794 (2019). https://doi.org/10.1016/j.bja.2019.07.027 Bekker, A., Sturaitis, M.K.: Dexmedetomidine for neurological surgery. Neurosurgery 57 Supplement, 1–10; discussion 1–10; discussion 1 (2005). https://doi.org/10.1227/01.neu.0000163476.42034.a1 Lee, J. H., Ki, M., Choi, S., Woo, C. J., Kim, D., Lim, H., Kim, D. C.: Validity and reliability of the Korean version of the Quality of Recovery-15 questionnaire. Korean J. Anesthesiol. 74, 142–149 (2021). https://doi.org/10.4097/kja.20435 Kang, R., Jeong, J. S., Ko, J. S., Lee, S. Y., Lee, J. H., Choi, S. J., Cha, S., Lee, J. J.: Intraoperative dexmedetomidine attenuates norepinephrine levels in patients undergoing transsphenoidal surgery: A randomized, placebo-controlled trial. BMC Anesthesiol. 20, 100 (2020). https://doi.org/10.1186/s12871-020-01025-7 Choi, S., Kim, Y. J., Oh, H., Kim, N., Kim, Y. H., & Park, H. P.: Sevoflurane anesthesia rather than propofol anesthesia is associated with 3-month postoperative hypocortisolism in patients undergoing endoscopic transsphenoidal surgery for non-functional pituitary adenoma with preoperative normal hypothalamic-pituitary-adrenal axis. Acta Neurochir (Wien). 164, 2083-2094 (2022). https://doi.org/10.1007/s00701-022-05260-4 Kim, J. H., Lee, J. H., Lee, J. H., Hong, A. R., Kim, Y. J., Kim, Y. H.: Endoscopic Transsphenoidal Surgery Outcomes in 331 Nonfunctioning Pituitary Adenoma Cases After a Single Surgeon Learning Curve. World Neurosurg. 109, e409-e416 (2018). https://doi.org/10.1016/j.wneu.2017.09.194 Johnson, A., Rice, A.N., Titch, J.F., Gupta, D.K.: Identifying components necessary for an enhanced recovery after surgery pathway for elective intracranial surgery: An improvement project using the quality of Recovery-15 score. World Neurosurg. 130, e423–e430 (2019). https://doi.org/10.1016/j.wneu.2019.06.108 Elayat, A., Jena, S.S., Nayak, S., Sahu, R.N., Tripathy, S.: Enhanced recovery after surgery – ERAS in elective craniotomies-a non-randomized controlled trial. BMC Neurol. 21, 127 (2021). https://doi.org/10.1186/s12883-021-02150-7 Bala, R., Chaturvedi, A., Pandia, M.P., Bithal, P.K.: Intraoperative dexmedetomidine maintains hemodynamic stability and hastens postoperative recovery in patients undergoing transsphenoidal pituitary surgery. J. Neurosci. Rural Pract. 10, 599–605 (2019). https://doi.org/10.1055/s-0039-3399402 Liu, Z., Gao, C., Liu, C., Liu, W., Xu, X., Ma, T., Du, X., Shen, J.: Supplementation with dexmedetomidine for transsphenoidal resection of pituitary adenoma: A meta-analysis of randomized controlled trials. Clin. Neuropharmacol. 44, 17–20 (2021). https://doi.org/10.1097/WNF.0000000000000426 Gopalakrishna, K.N., Dash, P.K., Chatterjee, N., Easwer, H.V., Ganesamoorthi, A.: Dexmedetomidine as an anesthetic adjuvant in patients undergoing transsphenoidal resection of pituitary tumor. J. Neurosurg. Anesthesiol. 27, 209–215 (2015). https://doi.org/10.1097/ANA.0000000000000144 Ledowski, T., Bein, B., Hanss, R., Paris, A., Fudickar, W., Scholz, J., Tonner, P. H.: Neuroendocrine stress response and heart rate variability: A comparison of total intravenous versus balanced anesthesia. Anesth. Analg. 101, 1700–1705 (2005). https://doi.org/10.1213/01.ane.0000184041.32175.14 Kostopanagiotou, G., Kalimeris, K., Christodoulaki, K., Nastos, C., Papoutsidakis, N., Dima, C., Chrelias, C., Pandazi, A., Mourouzis, I., Pantos, C.: The differential impact of volatile and intravenous anaesthetics on stress response in the swine. Hormones (Athens) 9, 67–75 (2010). https://doi.org/10.14310/horm.2002.1255 Winterhalter, M., Brandl, K., Rahe-Meyer, N., Osthaus, A., Hecker, H., Hagl, C., Adams, H. A., Piepenbrock, S.: Endocrine stress response and inflammatory activation during CABG surgery. A randomized trial comparing remifentanil infusion to intermittent fentanyl. Eur. J. Anaesthesiol. 25, 326–335 (2008). https://doi.org/10.1017/S0265021507003043 Ouyang, R., Ren, H., Liu, W., Yuan, X., Lei, E.: Remifentanil inhibits the traumatic stress response in emergent trauma surgery. J. Clin. Lab. Anal. 33, e22971 (2019). https://doi.org/10.1002/jcla.22971 Bergmann, I., Szabanowski, T., Bräuer, A., Crozier, T. A., Bauer, M., Hinz, J. M.: Remifentanil added to sufentanil-sevoflurane anesthesia suppresses hemodynamic and metabolic stress responses to intense surgical stimuli more effectively than high-dose sufentanil-sevoflurane alone. BMC Anesthesiol. 15, 3 (2015). https://doi.org/10.1186/1471-2253-15-3 Shariffuddin, I.I., Teoh, W.H., Wahab, S., Wang, C.Y.: Effect of single-dose dexmedetomidine on postoperative recovery after ambulatory ureteroscopy and ureteric stenting: A double blind randomized controlled study. BMC Anesthesiol. 18, 3 (2018). https://doi.org/10.1186/s12871-017-0464-6 Jiang, M., Sun, Q., Liu, G., Qu, H., Ma, J.: Efficacy of dexmedetomidine in reducing post-operative pain and improving the quality of recovery in patients with burn wounds undergoing tangential excision skin grafting. Exp. Ther. Med. 17, 1776–1782 (2019). https://doi.org/10.3892/etm.2019.7155 Kim, S.Y., Kim, J.M., Lee, J.H., Song, B.M., Koo, B.N.: Efficacy of intraoperative dexmedetomidine infusion on emergence agitation and quality of recovery after nasal surgery. Br. J. Anaesth. 111, 222–228 (2013). https://doi.org/10.1093/bja/aet056 Lee, S. H., Lee, C. Y., Lee, J. G., Kim, N., Lee, H. M., Oh, Y. J.: Intraoperative dexmedetomidine improves the quality of recovery and postoperative pulmonary function in patients undergoing video-assisted thoracoscopic surgery: A CONSORT-prospective, randomized, controlled trial. Med. (Baltim.) 95, e2854 (2016). https://doi.org/10.1097/MD.0000000000002854 Sherif, A.A., Elsersy, H.E.: The impact of dexmedetomidine or Xylocaine continuous infusion on opioid consumption and recovery after laparoscopic sleeve gastrectomy. Minerva Anestesiol. 83, 1274–1282 (2017). https://doi.org/10.23736/S0375-9393.17.11855-9 Zhang, L.Y., Zhang, Y.H., Shen, J., Luo, Y.: Effects of dexmedetomidine on post-operative recovery and mental status in patients receiving robotic-assisted thoracic surgery. Ann. Palliat. Med. 8, 469–475 (2019). https://doi.org/10.21037/apm.2019.08.09 Flynn, B.C., Nemergut, E.C.: Postoperative nausea and vomiting and pain after transsphenoidal surgery: A review of 877 patients. Anesth. Analg. 103, 162–167, table of contents (2006). https://doi.org/10.1213/01.ane.0000221185.08155.80 Labaf, A., Asghari, F., Samadi, S., Abdollahi, A., Zobeiry, S., Molavi, K.: Experiences of conscious patients undergoing tracheal intubation: A qualitative study. Arch. Anesthesiol. Crit. Care 8, 3–10 (2022). https://doi.org/10.18502/aacc.v8i1.8237 Arcangeli, A., D’Alò, C., Gaspari, R.: Dexmedetomidine use in general anaesthesia. Curr. Drug Targets 10, 687–695 (2009). https://doi.org/10.2174/138945009788982423 Kaur, M., Singh, P.M.: Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth. Essays Res. 5, 128–133 (2011). https://doi.org/10.4103/0259-1162.94750 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-4149671","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":283745581,"identity":"5eda6b96-035f-486d-b1b7-a5a2d3e9b99e","order_by":0,"name":"Seungeun Choi","email":"","orcid":"","institution":"Seoul National University Hospital, Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Seungeun","middleName":"","lastName":"Choi","suffix":""},{"id":283745582,"identity":"68cee4cb-eacd-4b31-b1d0-9d7c5baa0294","order_by":1,"name":"Han Byeol Lim","email":"","orcid":"","institution":"Seoul National University Hospital, Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Han","middleName":"Byeol","lastName":"Lim","suffix":""},{"id":283745583,"identity":"6be10758-319d-4233-ac76-b954a8856ef8","order_by":2,"name":"Kyong Won Shin","email":"","orcid":"","institution":"Seoul National University Hospital, Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Kyong","middleName":"Won","lastName":"Shin","suffix":""},{"id":283745584,"identity":"c7653f95-2f1b-4845-89aa-ee2eb6b43fab","order_by":3,"name":"Hyongmin Oh","email":"","orcid":"","institution":"Seoul National University Hospital, Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Hyongmin","middleName":"","lastName":"Oh","suffix":""},{"id":283745585,"identity":"e91c8ed7-ed62-4e7d-b562-f2e1d095c5d9","order_by":4,"name":"Yong Hwy Kim","email":"","orcid":"","institution":"Seoul National University Hospital, Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Yong","middleName":"Hwy","lastName":"Kim","suffix":""},{"id":283745586,"identity":"0c89d99a-d3e3-47d8-9a82-514b4e35b527","order_by":5,"name":"Jung Hee Kim","email":"","orcid":"","institution":"Seoul National University Hospital, Seoul National University College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Jung","middleName":"Hee","lastName":"Kim","suffix":""},{"id":283745587,"identity":"f597c87f-d3db-4386-a2e1-3b7c8688fab4","order_by":6,"name":"Hee-Pyoung Park","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYBACAzB5wAbGTyBaSxrpWg6ToMVcuvfg54oz5+3NJRIYP/xgSMsnqMVyzrlkyTM3bifunJHALNnDkGPZQNBhN3IMJBs+3E4wuJHAIM3AUGFA0BagFuOfDR/O2QO1MP8mVouZZMONA4wbbiSwAW3JIULLnXNplg1nkhM3nHnYZtljkEaEltu9h282HLOzNziefPjGj4pkwloYJHhgLMYGWDQRrWUUjIJRMApGAQ4AAKW1P0Og2FhwAAAAAElFTkSuQmCC","orcid":"","institution":"Seoul National University Hospital, Seoul National University College of Medicine","correspondingAuthor":true,"prefix":"","firstName":"Hee-Pyoung","middleName":"","lastName":"Park","suffix":""}],"badges":[],"createdAt":"2024-03-22 12:16:38","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4149671/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4149671/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":53582272,"identity":"5394adcf-b4cf-4175-812f-6db2b5fa42ae","added_by":"auto","created_at":"2024-03-27 17:40:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":53585,"visible":true,"origin":"","legend":"\u003cp\u003eConsolidated Standards of Reporting Trials flow diagram\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4149671/v1/000227c06e3554c247853dfd.png"},{"id":53630264,"identity":"adbc6459-ece7-4d17-af65-83d8f463d035","added_by":"auto","created_at":"2024-03-28 09:43:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":426030,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4149671/v1/f3402223-3028-4cde-a6e5-353f4b2c4d43.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of intraoperative dexmedetomidine on early postoperative quality of recovery in patients undergoing endoscopic transsphenoidal surgery for non-functioning pituitary adenoma: a randomized controlled trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSurgical stress response refers to physiological reactions to surgical trauma involving neuroendocrine, immunologic, and metabolic changes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Surgical stimuli release various stress hormones (e.g., cortisol and catecholamine) and inflammatory cytokines (e.g., tumor necrosis factor alpha and various interleukins) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Stress hormones and inflammatory mediators are associated with postoperative infection, delayed wound healing, and multiple organ dysfunction, ultimately resulting in impaired postoperative quality of recovery (QoR) [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn patients with nonfunctioning pituitary adenoma (NFPA) undergoing endoscopic transsphenoidal surgery (ETS), the surgical stress response may be more intense and complex than in other surgical patients. Surgical manipulation directly damages the pituitary gland, which plays a major role in regulating the endocrine system [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In addition, patients with NFPA are at risk of an impaired hypothalamic-pituitary-adrenal axis as the mass effect caused by NFPA can lead to mechanical pressure on the normal pituitary gland and deviation of the pituitary stalk [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Therefore, it is important to appropriately manage the surgical stress response in patients with NFPA undergoing ETS.\u003c/p\u003e \u003cp\u003eDexmedetomidine, a selective α2-adrenergic agonist, provides sedation and pain relief and inhibits the sympathetic nervous system [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Recently, it has been recognized as a major anesthetic adjuvant in enhanced recovery after surgery (ERAS) programs to decrease postoperative pain [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In addition, a previous meta-analysis demonstrated that intraoperative dexmedetomidine use attenuates perioperative stress responses and inflammatory reactions in various surgical patients [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In neurosurgical patients, dexmedetomidine is widely used because of its ability to reduce perioperative opioid consumption, stabilize intraoperative hemodynamics, and alleviate the surgical stress response [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. However, no study has determined whether dexmedetomidine improves the postoperative QoR in patients with NFPA undergoing ETS.\u003c/p\u003e \u003cp\u003eThis study hypothesized that intraoperative dexmedetomidine administration would improve early postoperative QoR by reducing the surgical stress response and postoperative pain in patients with NFPA undergoing ETS. In this study, the Korean version of the QoR-15 was used to assess the postoperative QoR [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. The QoR-15 score on postoperative day 1 was compared between patients who received intraoperative dexmedetomidine and those who did not. In addition, perioperative pituitary hormone levels, including cortisol levels, intraoperative serum interleukin-6 levels, postoperative pain scores, and the incidence of postoperative complications were compared.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eEthics\u003c/p\u003e \u003cp\u003e This randomized controlled trial was approved by the Institutional Review Board of Seoul National University Hospital (number: H-2106-149-1230, date: July 22, 2021) and registered at ClinicalTrials.gov (NCT number: 05005715, date: August 13, 2021). This study followed the Good Clinical Practice guidelines, and the manuscript was written according to the applicable Consolidated Standard of Reporting Trials guidelines. Written informed consent was obtained from all patients before their participation in the study.\u003c/p\u003e \u003cp\u003eSubjects\u003c/p\u003e \u003cp\u003ePatients aged 20\u0026ndash;65 years with NFPA who were scheduled to undergo ETS under general anesthesia were included in this study. Patients who had a contraindication to dexmedetomidine (known hypersensitivity to dexmedetomidine, uncontrolled hypertension, severe left ventricular dysfunction, and second- or third-degree heart block); a previous history of ETS within a year; coagulopathy; psychiatric disorder; difficulty in completing the QoR-15 questionnaire; myasthenia gravis or myasthenic syndrome; history of hypersensitivity to propofol, remifentanil, and rocuronium; pregnancy; or breastfeeding were excluded. Patients who had undergone preoperative steroid replacement were also excluded.\u003c/p\u003e \u003cp\u003eRandomization\u003c/p\u003e \u003cp\u003eGroup randomization using computer-generated four-sized blocks was performed by an anesthesiologist who was not involved in the study. The patients were randomly assigned to either the dexmedetomidine or control group based on the allocation sequence in a 1:1 ratio. The allocation sequence was contained in sealed envelopes and disclosed before anesthesia induction by a nurse in charge of preparing the study or control drugs in the same volume. As a result, the anesthesiologists, surgeons, and patients were blinded to the randomization.\u003c/p\u003e \u003cp\u003eStudy protocol\u003c/p\u003e \u003cp\u003eBefore surgery, the serum levels of pituitary hormones (adrenocorticotropic hormone [ACTH], cortisol, triiodothyronine [T3], thyroxine [T4], thyroid stimulating hormone [TSH], growth hormone [GH], insulin-like growth factor 1 [IGF-1], luteinizing hormone [LH], follicle-stimulating hormone [FSH], and prolactin) were measured, and preoperative QoR was evaluated using the QoR-15 questionnaire.\u003c/p\u003e \u003cp\u003eThe patients entered the operating room without premedication and were monitored using pulse oximetry, electrocardiography, and noninvasive blood pressure measurements. Anesthesia was induced with continuous infusion of propofol (effect site concentration: 4 \u0026micro;g/mL) and remifentanil (effect site concentration: 4 ng/mL) using a target-controlled device (Orchestra base primea, Fresenius Kabi, Bad Homburg, Germany). After confirming loss of consciousness, rocuronium (0.6\u0026ndash;0.8 mg/kg) was administered to facilitate tracheal intubation. Intravenous acetaminophen (1,000 mg) was administered for preemptive analgesia. After tracheal intubation, an arterial catheter was placed in the patient\u0026rsquo;s radial artery for continuous blood pressure monitoring, and an additional peripheral venous catheter was placed in the patient\u0026rsquo;s forearm for fluid infusion and drug administration. During anesthetic maintenance, the effect site concentrations of propofol and remifentanil were adjusted to maintain blood pressure within \u0026plusmn;\u0026thinsp;20% of preoperative value and a bispectral index of 30\u0026ndash;60. Rocuronium was not administered after tracheal intubation. Mechanical ventilation was controlled to maintain normocapnia.\u003c/p\u003e \u003cp\u003eAfter anesthetic induction, in the dexmedetomidine group, a loading dose of dexmedetomidine at 1 \u0026micro;g/kg was administered intravenously over 10 min, followed by a maintenance dose of dexmedetomidine at 0.5 \u0026micro;g/kg/h continuous infusion until the end of surgery [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In the control group, normal saline was intravenously administered with the same loading volume of dexmedetomidine for 10 min and continuously infused at the same maintenance dose of dexmedetomidine until the end of surgery.\u003c/p\u003e \u003cp\u003eWhen tumor resection began, blood samples were collected to measure intraoperative pituitary hormones (ACTH, cortisol, T3, T4, TSH, GH, IGF-1, LH, FSH, prolactin, and antidiuretic hormones [ADH]) in both groups. Intraoperative serum interleukin-6 (IL-6) levels were simultaneously measured. Intravenous ramosetron (0.3 mg) and fentanyl (100 \u0026micro;g) were administered 30 min before the end of surgery to prevent postoperative nausea and vomiting (PONV) and postoperative pain. After surgery, patients underwent immediate postoperative brain computed tomography (CT) in the operating room. Subsequently, the administration of propofol, remifentanil, and either dexmedetomidine or normal saline was discontinued, and the patients were transferred to the neurointensive care unit without receiving any additional sedatives or neuromuscular blocking agents. After admission to the neurointensive care unit, immediate postoperative pituitary hormone (ACTH, cortisol, T3, T4, TSH, GH, IGF-1, LH, FSH, and prolactin) tests were conducted. Extubation was performed in the neurointensive care unit when the patients were alert and their spontaneous breathing had sufficiently recovered. The times to emergence and extubation were recorded.\u003c/p\u003e \u003cp\u003ePostoperative QoR was assessed using the QoR-15 questionnaire on postoperative day 1. Briefly, patients were asked 15 questions to assess five domains of patient-reported health status: physical comfort, physical independence, psychological support, emotional state, and pain. The 11-point numerical rating scale of 15 items has a minimum score of 0 (very poor recovery) and a maximum score of 150 (excellent recovery) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Postoperative cortisol levels were measured on postoperative days 1, 2, and 3. Intravenous acetaminophen (1,000 mg) and oral acetaminophen (650 mg) were administered every 8 h before and after resuming oral fluids, respectively. If a patient complained of PONV, intravenous ramosetron (0.3 mg) or metoclopramide (10 mg) was administered. Postoperative pain scores were assessed using a numeric rating scale (NRS; 0, no pain; 10, worst pain imaginable) at 4, 24, and 48 h postoperatively. If NRS score of \u0026ge;\u0026thinsp;4 was noted, a rescue analgesic (acetaminophen [1000 mg], ketorolac [30 mg], or fentanyl [50 \u0026micro;g]) was intravenously administered. The incidence of rescue analgesic administration and PONV was investigated at 4, 24, and 48 h postoperatively. The incidence of postoperative complications, such as diabetes insipidus, hyponatremia, infection, cerebrospinal fluid leakage, hemorrhage, and hydrocephalus, was noted. Postoperative pituitary function outcomes were investigated 3 months postoperatively.\u003c/p\u003e \u003cp\u003eStudy outcomes\u003c/p\u003e \u003cp\u003eThe primary outcome measure was the QoR-15 score on postoperative day 1. Secondary outcome measures included preoperative QoR-15 score, perioperative pituitary hormone levels (ACTH, cortisol, T3, T4, TSH, GH, IGF-1, LH, FSH, prolactin, and ADH), intraoperative serum IL-6 levels, postoperative pain scores, incidence of postoperative complications, and pituitary functional outcome at 3 months postoperatively.\u003c/p\u003e \u003cp\u003eACTH deficiency was diagnosed in the following cases: serum cortisol\u0026thinsp;\u0026lt;\u0026thinsp;18 \u0026micro;g/dL in the insulin-induced hypoglycemia test, peak cortisol\u0026thinsp;\u0026lt;\u0026thinsp;18 \u0026micro;g/dL in the short ACTH test, morning cortisol\u0026thinsp;\u0026lt;\u0026thinsp;8 \u0026micro;g/dL, or random cortisol\u0026thinsp;\u0026lt;\u0026thinsp;5 \u0026micro;g/dL with a low to normal serum ACTH level [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. TSH deficiency was defined as free T4\u0026thinsp;\u0026lt;\u0026thinsp;0.7 ng/dL with a low to normal TSH level [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. GH deficiency was identified when peak GH\u0026thinsp;\u0026lt;\u0026thinsp;3 ng/mL in the insulin-induced hypoglycemia test; if insulin-induced hypoglycemia test was not conducted, GH deficiency was determined by IGF-1 level below normal range, accompanied by deficiencies in ACTH, TSH, and gonadotropin [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Gonadotropin deficiency in men was defined as testosterone\u0026thinsp;\u0026lt;\u0026thinsp;2.7 ng/mL with a low to normal FSH/LH level. In premenopausal women, gonadotropin deficiency was determined by the presence of menstrual disorders [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Normal menopause was defined as FSH\u0026thinsp;\u0026gt;\u0026thinsp;30 mIU/mL and estradiol\u0026thinsp;\u0026lt;\u0026thinsp;50 pg/mL in female patients with GN deficiency [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSample size calculation\u003c/p\u003e \u003cp\u003eIn a previous study, postoperative QoR-15 score on postoperative day 1 was 134.3\u0026thinsp;\u0026plusmn;\u0026thinsp;17.3 in patients who underwent elective craniotomy [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Assuming that postoperative QoR-15 score increases by 10% when dexmedetomidine is administered, a minimum sample size of 27 patients was needed in each group when setting the α and β to 0.05 and 0.2, respectively. Considering a drop rate of 15%, 64 patients were required.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were conducted using the SPSS software (version 25, IBM Corp., Armonk, NY, USA). Categorical variables were presented as the number of patients (proportion), and continuous variables were presented as mean (standard deviation) or median (interquartile range). Pearson\u0026rsquo;s chi-square test or Fisher\u0026rsquo;s exact test was used to compare categorical variables based on the expected cell counts. For continuous variables, the Shapiro\u0026ndash;Wilk test was first used to assess the normality of data distribution, and the Student\u0026rsquo;s t-test and Mann\u0026ndash;Whitney U-test were used to compare normally distributed and skewed data, respectively. The time \u0026times; group effects of perioperative pituitary hormone levels and postoperative pain scores were evaluated using repeated-measures analysis of variance. If a significant time \u0026times; group effect was observed, Bonferroni correction with compensating for multiple comparisons was applied to compare the variables between the two groups at each time point: an alpha of 0.008 (0.05/6) was applied for perioperative serum cortisol levels, and 0.017 (0.05/3) was applied for perioperative serum levels of other pituitary hormones (ACTH, T3, T4, TSH, GH, IGF-1, LH, FSH, and prolactin) and postoperative pain scores. For other variables, p value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eIn total, 64 patients were enrolled between August 2021 and April 2023 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Among these patients, three (one withdrawal of consent and two preoperative steroid administrations) were excluded from the dexmedetomidine group. Finally, 29 patients in the dexmedetomidine group and 32 patients in the control group were included in the analysis. There were no significant differences in demographics, preoperative pituitary hormone levels, tumor characteristics, or the extent of surgical resection between the dexmedetomidine and control groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Intraoperative mean blood pressure (87.2 (81.3\u0026ndash;94.0) vs. 78.9 (75.9\u0026ndash;85.3) mmHg, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) was higher and the value of bispectral index (35.0 (31.5\u0026ndash;40.7) vs. 41.3 (36.7\u0026ndash;45.7), P\u0026thinsp;=\u0026thinsp;0.002) was lower in the dexmedetomidine group than the control group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of demographic and intraoperative variables between the dexmedetomidine and control 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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDexmedetomidine group (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (yr)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51.0 (40.5\u0026ndash;59.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50.0 (42.0\u0026ndash;57.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.971\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale sex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (44.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17 (53.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.696\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeight (cm)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e164.4 (156.6\u0026ndash;172.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e164.2 (159.3\u0026ndash;170.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.778\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e65.5 (58.5\u0026ndash;77.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e68.0 (57.6\u0026ndash;76.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.868\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody mass index (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25.1 (23.0\u0026ndash;27.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25.0 (22.1\u0026ndash;28.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eASA PS class\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.541\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eI\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (48.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19 (59.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eII\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (51.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e13 (40.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative serum level of pituitary hormones\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCortisol (\u0026micro;g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.4 (4.8\u0026ndash;12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.3 (5.7\u0026ndash;15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACTH (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26.8 (17.9\u0026ndash;43.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e23.8 (16.1\u0026ndash;45.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.929\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3 (ng/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e121.0 (102.5\u0026ndash;130.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e120.5 (102.5\u0026ndash;139.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.670\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4 (ng/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.06 (0.96\u0026ndash;1.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.04 (0.93\u0026ndash;1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.418\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH (\u0026micro;IU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.50 (0.96\u0026ndash;2.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.43 (1.01\u0026ndash;2.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.544\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH (mIU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.2 (1.4\u0026ndash;3.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.0 (1.5\u0026ndash;3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.925\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH (mIU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.6 (3.2\u0026ndash;8.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.5 (3.5\u0026ndash;7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.874\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIGF-1 (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e109.0 (62.0\u0026ndash;149.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e91.0 (70.5\u0026ndash;131.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.745\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGH (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.30 (0.09\u0026ndash;0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.21 (0.08\u0026ndash;0.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.732\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProlactin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14.5 (5.9\u0026ndash;46.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18.5 (6.7\u0026ndash;36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative pituitary hormone deficiency\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACTH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.411\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGonadotropin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor characteristics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTumor volume (cm\u003csup\u003e3\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4.78 (3.25\u0026ndash;7.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5.62 (3.06\u0026ndash;7.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.697\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOptic chiasm compression\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (75.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e25 (78.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCavernous sinus invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (18.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDegree of resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.338\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGrossly total resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26 (89.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31 (96.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSubtotal resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative CSF leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (18.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnesthesia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnesthetic time (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e125.0 (105.0\u0026ndash;142.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e120.0 (111.3\u0026ndash;145.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.891\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative vital signs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHeart rate (beats/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.3 (57.2\u0026ndash;69.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e61.7 (57.2\u0026ndash;68.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.751\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean blood pressure (mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e87.2 (81.3\u0026ndash;94.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e78.9 (75.9\u0026ndash;85.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBody temperature (℃)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36.1 (35.8\u0026ndash;36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36.0 (35.6\u0026ndash;36.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.466\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBispectral index\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35.0 (31.5\u0026ndash;40.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e41.3 (36.7\u0026ndash;45.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfusion rate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePropofol (mg/kg/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.15 (0.13\u0026ndash;0.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.15 (0.13\u0026ndash;0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.479\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemifentanil (\u0026micro;g/kg/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.15 (0.12\u0026ndash;0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.15 (0.14\u0026ndash;0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003eASA PS, American Society of Anesthesiologists physical status; ACTH, adrenocorticotropic hormone; TSH: thyroid stimulating hormone; GH: growth hormone; CSF, cerebrospinal fluid\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThere was no significant difference in the QoR-15 score on postoperative day 1 between the dexmedetomidine and control groups (94.0 [78.0\u0026ndash;114.0] vs. 92.5 [68.3\u0026ndash;110.8], P\u0026thinsp;=\u0026thinsp;0.598) (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 perioperative Quality of Recovery-15 scores between the dexmedetomidine and control 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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDexmedetomidine group (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMedian difference (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQoR-15 score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePreoperative day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e141.0 (125.5\u0026ndash;148.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e141.0 (129.3\u0026ndash;147.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (-6.0\u0026ndash;6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.816\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical comfort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48.0 (43.0\u0026ndash;50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50.0 (44.0\u0026ndash;50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (-3.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical independence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20.0 (20.0\u0026ndash;20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20.0 (20.0\u0026ndash;20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.770\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychological support\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20.0 (20.0\u0026ndash;20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20.0 (20.0\u0026ndash;20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.192\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmotions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36.0 (30.0\u0026ndash;38.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36.0 (27.0\u0026ndash;39.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (-2.0-3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.827\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e20.0 (15.5\u0026ndash;20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e20.0 (19.0\u0026ndash;20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.329\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative day 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e94.0 (78.0\u0026ndash;114.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e92.5 (68.3\u0026ndash;110.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.0 (-11.0\u0026ndash;18.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.598\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical comfort\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28.0 (16.0\u0026ndash;39.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.5 (25.5\u0026ndash;40.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-6.0 (-13.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysical independence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.0 (3.5\u0026ndash;14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7.0 (2.0\u0026ndash;15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (-3.0\u0026ndash;4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.805\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsychological support\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19.0 (15.0\u0026ndash;20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e17.0 (13.0\u0026ndash;20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEmotions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30.0 (23.5\u0026ndash;36.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e27.0 (19.0\u0026ndash;34.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.0 (-2.0\u0026ndash;8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.275\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.0 (8.0\u0026ndash;15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.0 (8.3\u0026ndash;15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.0 (-2.0\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.602\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\u003eQoR, Quality of Recovery; CI, confidence interval.\u003c/p\u003e \u003cp\u003ePerioperative serum cortisol levels (preoperative, intraoperative, immediate postoperative, and on postoperative days 1, 2, and 3) showed no significant time \u0026times; group effects (P\u0026thinsp;=\u0026thinsp;0.578). In addition, other perioperative pituitary hormone levels (preoperative, intraoperative, and immediately postoperative) showed no significant time \u0026times; group effects. Intraoperative serum IL-6 levels did not differ significantly between the two groups (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 intraoperative and postoperative pituitary hormone and intraoperative interleukin-6 levels between the dexmedetomidine and control 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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDexmedetomidine group (n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group (n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMedian difference (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntraoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCortisol (\u0026micro;g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.5 (18.5\u0026ndash;4.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10.1 (4.7\u0026ndash;15.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.0 (-4.4\u0026ndash;2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.608\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACTH (pg/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22.8 (12.1\u0026ndash;44.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28.0 (16.9\u0026ndash;60.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-4.9 (-15.2\u0026ndash;5.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3 (ng/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e99.0 (89.5\u0026ndash;106.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e97.5 (88.0\u0026ndash;110.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.0 (-11.0\u0026ndash;5.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.492\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4 (ng/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.13 (1.03\u0026ndash;1.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.14 (1.02\u0026ndash;1.26)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.01 (-0.09\u0026ndash;0.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.800\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH (\u0026micro;IU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.17 (0.67\u0026ndash;2.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.32 (0.85\u0026ndash;2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.25 (-0.76\u0026ndash;0.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH (mIU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.8 (1.2\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.0 (1.2\u0026ndash;2.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1 (-0.6\u0026ndash;0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.795\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH (mIU/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.5 (3.3\u0026ndash;8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.3 (3.0\u0026ndash;6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8 (-1.0\u0026ndash;2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.457\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIGF-1 (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e83.0 (51.0\u0026ndash;121.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86.5 (63.5\u0026ndash;130.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-6.0 (-30.0\u0026ndash;19.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.686\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGH (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.84 (0.19\u0026ndash;2.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.27 (0.09\u0026ndash;0.44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33 (0.02\u0026ndash;0.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.026\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProlactin (ng/mL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28.2 (9.5\u0026ndash;50.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28.7 (12.0\u0026ndash;53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.7 (-14.6\u0026ndash;7.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.583\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eADH (pmol/L)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.7 (0.8\u0026ndash;4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0 (0.8\u0026ndash;6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (-0.2\u0026ndash;0.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.586\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterleukin-6 (pg/mL)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.78 (1.50\u0026ndash;2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.75 (1.50\u0026ndash;2.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00 (-0.37\u0026ndash;0.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.974\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmediate postoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCortisol (\u0026micro;g/dL)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19.1 (24.6\u0026ndash;15.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19.2 (16.1\u0026ndash;23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.6 (-4.5\u0026ndash;2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.723\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACTH (pg/mL)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e133.3 (42.0\u0026ndash;164.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e133.1 (71.9\u0026ndash;220.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-12.3 (-64.2\u0026ndash;41.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.610\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT3 (ng/dL)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e95.0 (85.0\u0026ndash;112.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e104.0 (91.5\u0026ndash;112.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-5.0 (-14.0\u0026ndash;4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.322\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eT4 (ng/dL)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.18 (1.00\u0026ndash;1.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.12 (1.03\u0026ndash;1.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.03 (-0.06\u0026ndash;0.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.599\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH (\u0026micro;IU/mL)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.78 (0.96\u0026ndash;3.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.69 (1.54\u0026ndash;4.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.70 (-1.60\u0026ndash;0.11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.093\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLH (mIU/mL)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.6 (1.4\u0026ndash;3.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.2 (1.4\u0026ndash;3.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.1 (-0.6\u0026ndash;0.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.802\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFSH (mIU/mL)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.9 (3.4\u0026ndash;8.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4.6 (3.4\u0026ndash;6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.7 (-1.0\u0026ndash;2.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.353\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIGF-1 (ng/mL)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e77.0 (54.0\u0026ndash;116.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e86.5 (63.3\u0026ndash;118.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-8.5 (-29.0\u0026ndash;14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.451\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGH (ng/mL)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.46 (0.74\u0026ndash;2.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.13 (0.69\u0026ndash;2.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.16 (-0.39\u0026ndash;0.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.605\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProlactin (ng/mL)\u003csup\u003ed\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28.2 (9.5\u0026ndash;50.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28.7 (12.0\u0026ndash;53.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.8 (-12.4\u0026ndash;5.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.475\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative day 1\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCortisol (\u0026micro;g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21.1 (13.5\u0026ndash;28.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16.3 (7.8\u0026ndash;22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.6 (0.8\u0026ndash;10.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative day 2\u003csup\u003ee\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCortisol (\u0026micro;g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12.3 (8.4\u0026ndash;15.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11.5 (6.4\u0026ndash;16.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.3 (-2.7\u0026ndash;3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.756\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative day 3\u003csup\u003ef\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCortisol (\u0026micro;g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9.4 (5.2\u0026ndash;12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9.5 (3.2\u0026ndash;12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.8 (-2.0\u0026ndash;4.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.613\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\u003e \u003csup\u003ea\u003c/sup\u003e n\u0026thinsp;=\u0026thinsp;27 in the dexmedetomidine group and n\u0026thinsp;=\u0026thinsp;31 in the control group.\u003c/p\u003e \u003cp\u003e \u003csup\u003eb\u003c/sup\u003e n\u0026thinsp;=\u0026thinsp;10 in the dexmedetomidine group and n\u0026thinsp;=\u0026thinsp;12 in the control group.\u003c/p\u003e \u003cp\u003e \u003csup\u003ec\u003c/sup\u003e n\u0026thinsp;=\u0026thinsp;29 in the dexmedetomidine group and n\u0026thinsp;=\u0026thinsp;32 in the control group.\u003c/p\u003e \u003cp\u003e \u003csup\u003ed\u003c/sup\u003e n\u0026thinsp;=\u0026thinsp;27 in the dexmedetomidine group and n\u0026thinsp;=\u0026thinsp;32 in the control group.\u003c/p\u003e \u003cp\u003e \u003csup\u003ee\u003c/sup\u003e n\u0026thinsp;=\u0026thinsp;28 in the dexmedetomidine group and n\u0026thinsp;=\u0026thinsp;32 in the control group.\u003c/p\u003e \u003cp\u003e \u003csup\u003ef\u003c/sup\u003e n\u0026thinsp;=\u0026thinsp;28 in the dexmedetomidine group and n\u0026thinsp;=\u0026thinsp;30 in the control group.\u003c/p\u003e \u003cp\u003eACTH, adrenocorticotropic hormone; T3, triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone; GH, growth hormone; IGF-1, insulin-like factor 1; LH, luteinizing hormone; FSH, follicle-stimulating hormone; ADH, antidiuretic hormone; CI, confidence interval.\u003c/p\u003e \u003cp\u003eEmergence time (37.0 [24.0\u0026ndash;47.0] vs. 21.0 [12.3\u0026ndash;32.3] min, P\u0026thinsp;=\u0026thinsp;0.001) and extubation time (63.0 [40.0\u0026ndash;85.0] vs. 36.5 [18.3\u0026ndash;53.3] min, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were longer in the dexmedetomidine group than the control group (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). The postoperative pain scores showed a significant time \u0026times; group effect (P\u0026thinsp;=\u0026thinsp;0.027). The pain score was significantly lower in the dexmedetomidine group only at 4 h postoperatively (0.0 [0.0\u0026ndash;0.0] vs 1.0 [0.0\u0026ndash;3.0], P\u0026thinsp;=\u0026thinsp;0.003), while it did not differ at 24 and 48 h postoperatively. The total number of rescue analgesics administered, incidence of PONV and postoperative complications, and pituitary functional outcome at 3 months postoperatively did not differ between the two groups.\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 postoperative outcomes between the dexmedetomidine and control 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=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"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\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDexmedetomidine group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;29)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group \u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eProportional or Median difference (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to emergence (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e37.0 (26.5\u0026ndash;47.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21.0 (12.3\u0026ndash;32.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.0 (6.0\u0026ndash;22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to extubation (min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.0 (39.5\u0026ndash;81.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e36.5 (18.3\u0026ndash;53.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24.0 (11.0\u0026ndash;36.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative pain\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 h postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0 (0.0\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.0 (-2.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24 h postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.0 (2.0\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.0 (2.0\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.914\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48 h postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.0 (2.5\u0026ndash;3.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3.0 (2.0\u0026ndash;4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (-1.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.602\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal number of rescue analgesics administered\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 h postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.134\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24 h postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.5 (0.0\u0026ndash;1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (0.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.354\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48 h postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.0 (0.0\u0026ndash;1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.0 (0.0\u0026ndash;2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0 (-1.0\u0026ndash;0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative nausea and vomiting\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4 h postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.9% (-2.9\u0026ndash;16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e24 h postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-5.9% (-18.7\u0026ndash;6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.614\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e48 h postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (9.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-2.5% (-16.8\u0026ndash;11.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePituitary hormone deficiency at 3 months postoperatively\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACTH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2 (6.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.5% (-8.2\u0026ndash;23.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.577\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTSH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.9% (-2.9\u0026ndash;16.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.222\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (44.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (37.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.3% (-18.3\u0026ndash;32.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.749\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGonadotropin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e11 (37.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (34.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.6% (-21.5\u0026ndash;28.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.983\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePostoperative complications\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes insipidus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (20.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (21.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.2% (-22.5\u0026ndash;20.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyponatremia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5 (15.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-8.7% (-24.9\u0026ndash;7.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.429\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInfection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (3.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3.1% (-9.7\u0026ndash;3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCSF leakage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHemorrhage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHydrocephalus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.4% (-3.6\u0026ndash;10.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.475\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\u003e \u003csup\u003ea\u003c/sup\u003e Postoperative pain was assessed using a numeric rating scale (0, no pain; 10, worst pain imaginable). ACTH, adrenocorticotropic hormone; TSH, thyroid-stimulating hormone; GH, growth hormone; CSF, cerebrospinal fluid; CI, confidence interval; NA, not applicable.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eRecently, postoperative QoR has become a major concern for both anesthesiologists and surgeons. Various trials have been performed to improve postoperative QoR. This randomized controlled trial explored the impact of intraoperative dexmedetomidine administration on postoperative QoR in patients with NFPA undergoing ETS. This study showed that the intraoperative administration of dexmedetomidine did not improve postoperative QoR in such patients.\u003c/p\u003e \u003cp\u003eReducing the perioperative surgical stress response, one of the targets of the ERAS program [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], is very important for improving postoperative QoR. Dexmedetomidine has various beneficial effects, such as improving intraoperative hemodynamic stability, decreasing intraoperative norepinephrine release, and reducing the requirement for anesthetics and analgesics, when used as an anesthetic adjuvant in patients undergoing ETS [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan additionalcitationids=\"CR18\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. In this study, we believed that intraoperative dexmedetomidine would improve the postoperative QoR by reducing the surgical stress response. However, dexmedetomidine did not decrease serum levels of stress hormones or increase postoperative QoR-15 scores in this study. There were several reasons for this observation. First, propofol and remifentanil were used as the main anesthetics. Propofol attenuates surgical stress response by inhibiting the release of stress hormones, including cortisol, epinephrine, and norepinephrine, in response to surgical stimuli [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Remifentanil has also been reported to decrease the serum levels of surgical stress hormones during the perioperative period [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Such strong anti-stress effects of propofol and remifentanil may result in non-significant differences in the perioperative stress response and postoperative QoR when dexmedetomidine is used as an anesthetic adjuvant. In other words, we believe that the anti-stress effect of dexmedetomidine may be overwhelmed by that of propofol and remifentanil, possibly masking the beneficial effect of dexmedetomidine on the reduced stress response. Indeed, most previous studies have reported that additional intraoperative dexmedetomidine administration could help improve postoperative QoR when combined with inhalation anesthesia, but not when using propofol [\u003cspan additionalcitationids=\"CR26 CR27 CR28 CR29\" citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Second, ETS is a minimally invasive procedure involving a small incision and minimal normal tissue damage, resulting in less surgical stress responses [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Owing to the less invasive nature of ETS, the beneficial effect of dexmedetomidine on stress hormones was not evident. Third, the dexmedetomidine group required more time for extubation, and a prolonged intubated time may have compromised the postoperative QoR. Intubated patients experience various physical and psychological stresses, including discomfort, pain, inability to speak and communicate, anxiety, and fear [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Even within a short period, being intubated and mechanically ventilated in an awake state can result in the deterioration of postoperative QoR.\u003c/p\u003e \u003cp\u003ePostoperative pain directly affects the postoperative QoR. In this study, the analgesic effect of dexmedetomidine was statistically significant at 4 h postoperatively; however, the difference was not clinically significant. This can be attributed to the characteristics of the ETS and effective perioperative pain management. This minimally invasive surgical technique for ETS leads to reduced postoperative pain and inflammation [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Infiltration of the nasal mucosa with epinephrine and lidocaine during surgical preparation further reduces postoperative pain [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In addition, preemptive acetaminophen administration, fentanyl administration before the end of surgery, periodic administration of acetaminophen during the postoperative period, and active use of rescue analgesics would be helpful for postoperative pain relief. In other words, the analgesic effect of dexmedetomidine may not have been remarkable because postoperative pain was effectively controlled using a multimodal analgesia protocol.\u003c/p\u003e \u003cp\u003eIn addition, postoperative QoR can be negatively affected by opioid-related complications. Intraoperative dexmedetomidine potentiates the analgesic effects of opioids, thereby reducing perioperative opioid consumption [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. This decrease in opioid use can lead to reduced opioid-related side effects (PONV), contributing to an improved postoperative QoR. However, the study did not reduce intraoperative opioid consumption. This finding may be due to dexmedetomidine-induced hypertension [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]. Dexmedetomidine caused an increase in blood pressure at the beginning of the infusion, which necessitated the administration of a higher dose of remifentanil in the dexmedetomidine group. However, as the infusion continued, the need for remifentanil decreased, ultimately resulting in a similar overall remifentanil dose. In other words, an opioid-sparing effect was not observed in the dexmedetomidine group, which may partly explain the lack of improvement in postoperative QoR.\u003c/p\u003e \u003cp\u003eThis study had several limitations. First, this was a single-center study conducted on patients with NFPA who underwent ETS under total intravenous anesthesia. Therefore, these results cannot be generalized to other patients with functional pituitary tumors, those undergoing craniotomy for pituitary tumor removal, and those receiving inhalation anesthesia. Second, dexmedetomidine was administered at a fixed dose to all patients. Therefore, we could not determine whether the anti-stress effects of dexmedetomidine were dose dependent. In addition, only serum cortisol levels, a serum marker of stress response, were investigated in this study. Therefore, we did not know the effect of intraoperative dexmedetomidine on other serum markers of the stress response (i.e., epinephrine and norepinephrine). Third, the postoperative QoR was evaluated only on postoperative day 1. Therefore, we could not determine the time at which the postoperative QoR returned to baseline. Further studies are needed to explore the long-term effects of intraoperative dexmedetomidine on postoperative QoR.\u003c/p\u003e \u003cp\u003eIn conclusion, dexmedetomidine, as an anesthetic adjuvant, did not improve the postoperative QoR in patients with NFPA who underwent ETS under total intravenous anesthesia during ETS. Further research is warranted to identify ways to improve the postoperative QoR in such patients.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding: This study was funded by research grants funded by Seoul National University Hospital (Grant number: 0420210400).\u003c/p\u003e\n\u003cp\u003eConflict of Interest/Competing interests: The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003eEthics approval: This study was conducted in accordance with ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.\u003c/p\u003e\n\u003cp\u003eConsent to participate: Informed consent was obtained from all patients before participation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAvailability of data and material: The data and materials of this study are available upon request to the corresponding author.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHelander, E. M., Webb, M. P., Menard, B., Prabhakar, A., Helmstetter, J., Cornett, E. M., Urman, R. D., Nguyen, V. H., \u0026amp; Kaye, A. D.: Metabolic and the surgical stress response considerations to improve postoperative recovery. Curr. Pain Headache Rep. 23, 33 (2019). https://doi.org/10.1007/s11916-019-0770-4\u003c/li\u003e\n\u003cli\u003eKurosawa, S., Kato, M.: Anesthetics, immune cells, and immune responses. J. Anesth. 22, 263\u0026ndash;277 (2008). https://doi.org/10.1007/s00540-008-0626-2\u003c/li\u003e\n\u003cli\u003eBaigrie, R.J., Lamont, P.M., Kwiatkowski, D., Dallman, M.J., Morris, P.J.: Systemic cytokine response after major surgery. Br. J. Surg. 79, 757\u0026ndash;760 (1992). https://doi.org/10.1002/bjs.1800790813\u003c/li\u003e\n\u003cli\u003eHomburger, J.A., Meiler, S.E.: Anesthesia drugs, immunity, and long-term outcome. Curr. Opin. Anaesthesiol. 19, 423\u0026ndash;428 (2006). https://doi.org/10.1097/01.aco.0000236143.61593.14\u003c/li\u003e\n\u003cli\u003eKaplan, S.A.: The pituitary gland: A brief history. Pituitary 10, 323\u0026ndash;325 (2007). https://doi.org/10.1007/s11102-007-0050-x\u003c/li\u003e\n\u003cli\u003eYhim, H.B., Oh, H.M., Yoon, H.K., Kim, Y.H., Park, H.P.: A retrospective observational study of the neuroendocrine stress response in patients undergoing endoscopic transsphenoidal surgery for removal of pituitary adenomas: Total intravenous versus balanced anesthesia. J. Neurosurg. Anesthesiol. 33, 137\u0026ndash;146 (2021). https://doi.org/10.1097/ANA.0000000000000638\u003c/li\u003e\n\u003cli\u003eKhan, Z.P., Ferguson, C.N., Jones, R.M.: alpha-2 and imidazoline receptor agonists. Their pharmacology and therapeutic role. Anaesthesia 54, 146\u0026ndash;165 (1999). https://doi.org/10.1046/j.1365-2044.1999.00659.x\u003c/li\u003e\n\u003cli\u003eKaye, A. D., Chernobylsky, D. J., Thakur, P., Siddaiah, H., Kaye, R. J., Eng, L. K., Harbell, M. W., Lajaunie, J., Cornett, E. M.: Dexmedetomidine in enhanced recovery after surgery (ERAS) protocols for postoperative pain. Curr. Pain Headache Rep. 24, 21 (2020). https://doi.org/10.1007/s11916-020-00853-z\u003c/li\u003e\n\u003cli\u003eWang, K., Wu, M., Xu, J., Wu, C., Zhang, B., Wang, G., Ma, D.: Effects of dexmedetomidine on perioperative stress, inflammation, and immune function: Systematic review and meta-analysis. Br. J. Anaesth. 123, 777\u0026ndash;794 (2019). https://doi.org/10.1016/j.bja.2019.07.027\u003c/li\u003e\n\u003cli\u003eBekker, A., Sturaitis, M.K.: Dexmedetomidine for neurological surgery. Neurosurgery 57 Supplement, 1\u0026ndash;10; discussion 1\u0026ndash;10; discussion 1 (2005). https://doi.org/10.1227/01.neu.0000163476.42034.a1\u003c/li\u003e\n\u003cli\u003eLee, J. H., Ki, M., Choi, S., Woo, C. J., Kim, D., Lim, H., Kim, D. C.: Validity and reliability of the Korean version of the Quality of Recovery-15 questionnaire. Korean J. Anesthesiol. 74, 142\u0026ndash;149 (2021). https://doi.org/10.4097/kja.20435\u003c/li\u003e\n\u003cli\u003eKang, R., Jeong, J. S., Ko, J. S., Lee, S. Y., Lee, J. H., Choi, S. J., Cha, S., Lee, J. J.: Intraoperative dexmedetomidine attenuates norepinephrine levels in patients undergoing transsphenoidal surgery: A randomized, placebo-controlled trial. BMC Anesthesiol. 20, 100 (2020). https://doi.org/10.1186/s12871-020-01025-7\u003c/li\u003e\n\u003cli\u003eChoi, S., Kim, Y. J., Oh, H., Kim, N., Kim, Y. H., \u0026amp; Park, H. P.: Sevoflurane anesthesia rather than propofol anesthesia is associated with 3-month postoperative hypocortisolism in patients undergoing endoscopic transsphenoidal surgery for non-functional pituitary adenoma with preoperative normal hypothalamic-pituitary-adrenal axis. Acta Neurochir (Wien). 164, 2083-2094 (2022). https://doi.org/10.1007/s00701-022-05260-4\u003c/li\u003e\n\u003cli\u003eKim, J. H., Lee, J. H., Lee, J. H., Hong, A. R., Kim, Y. J., Kim, Y. H.: Endoscopic Transsphenoidal Surgery Outcomes in 331 Nonfunctioning Pituitary Adenoma Cases After a Single Surgeon Learning Curve. World Neurosurg. 109, e409-e416 (2018). https://doi.org/10.1016/j.wneu.2017.09.194\u003c/li\u003e\n\u003cli\u003eJohnson, A., Rice, A.N., Titch, J.F., Gupta, D.K.: Identifying components necessary for an enhanced recovery after surgery pathway for elective intracranial surgery: An improvement project using the quality of Recovery-15 score. World Neurosurg. 130, e423\u0026ndash;e430 (2019). https://doi.org/10.1016/j.wneu.2019.06.108\u003c/li\u003e\n\u003cli\u003eElayat, A., Jena, S.S., Nayak, S., Sahu, R.N., Tripathy, S.: Enhanced recovery after surgery \u0026ndash; ERAS in elective craniotomies-a non-randomized controlled trial. BMC Neurol. 21, 127 (2021). https://doi.org/10.1186/s12883-021-02150-7\u003c/li\u003e\n\u003cli\u003eBala, R., Chaturvedi, A., Pandia, M.P., Bithal, P.K.: Intraoperative dexmedetomidine maintains hemodynamic stability and hastens postoperative recovery in patients undergoing transsphenoidal pituitary surgery. J. Neurosci. Rural Pract. 10, 599\u0026ndash;605 (2019). https://doi.org/10.1055/s-0039-3399402\u003c/li\u003e\n\u003cli\u003eLiu, Z., Gao, C., Liu, C., Liu, W., Xu, X., Ma, T., Du, X., Shen, J.: Supplementation with dexmedetomidine for transsphenoidal resection of pituitary adenoma: A meta-analysis of randomized controlled trials. Clin. Neuropharmacol. 44, 17\u0026ndash;20 (2021). https://doi.org/10.1097/WNF.0000000000000426\u003c/li\u003e\n\u003cli\u003eGopalakrishna, K.N., Dash, P.K., Chatterjee, N., Easwer, H.V., Ganesamoorthi, A.: Dexmedetomidine as an anesthetic adjuvant in patients undergoing transsphenoidal resection of pituitary tumor. J. Neurosurg. Anesthesiol. 27, 209\u0026ndash;215 (2015). https://doi.org/10.1097/ANA.0000000000000144\u003c/li\u003e\n\u003cli\u003eLedowski, T., Bein, B., Hanss, R., Paris, A., Fudickar, W., Scholz, J., Tonner, P. H.: Neuroendocrine stress response and heart rate variability: A comparison of total intravenous versus balanced anesthesia. Anesth. Analg. 101, 1700\u0026ndash;1705 (2005). https://doi.org/10.1213/01.ane.0000184041.32175.14\u003c/li\u003e\n\u003cli\u003eKostopanagiotou, G., Kalimeris, K., Christodoulaki, K., Nastos, C., Papoutsidakis, N., Dima, C., Chrelias, C., Pandazi, A., Mourouzis, I., Pantos, C.: The differential impact of volatile and intravenous anaesthetics on stress response in the swine. Hormones (Athens) 9, 67\u0026ndash;75 (2010). https://doi.org/10.14310/horm.2002.1255\u003c/li\u003e\n\u003cli\u003eWinterhalter, M., Brandl, K., Rahe-Meyer, N., Osthaus, A., Hecker, H., Hagl, C., Adams, H. A., Piepenbrock, S.: Endocrine stress response and inflammatory activation during CABG surgery. A randomized trial comparing remifentanil infusion to intermittent fentanyl. Eur. J. Anaesthesiol. 25, 326\u0026ndash;335 (2008). https://doi.org/10.1017/S0265021507003043\u003c/li\u003e\n\u003cli\u003eOuyang, R., Ren, H., Liu, W., Yuan, X., Lei, E.: Remifentanil inhibits the traumatic stress response in emergent trauma surgery. J. Clin. Lab. Anal. 33, e22971 (2019). https://doi.org/10.1002/jcla.22971\u003c/li\u003e\n\u003cli\u003eBergmann, I., Szabanowski, T., Br\u0026auml;uer, A., Crozier, T. A., Bauer, M., Hinz, J. M.: Remifentanil added to sufentanil-sevoflurane anesthesia suppresses hemodynamic and metabolic stress responses to intense surgical stimuli more effectively than high-dose sufentanil-sevoflurane alone. BMC Anesthesiol. 15, 3 (2015). https://doi.org/10.1186/1471-2253-15-3\u003c/li\u003e\n\u003cli\u003eShariffuddin, I.I., Teoh, W.H., Wahab, S., Wang, C.Y.: Effect of single-dose dexmedetomidine on postoperative recovery after ambulatory ureteroscopy and ureteric stenting: A double blind randomized controlled study. BMC Anesthesiol. 18, 3 (2018). https://doi.org/10.1186/s12871-017-0464-6\u003c/li\u003e\n\u003cli\u003eJiang, M., Sun, Q., Liu, G., Qu, H., Ma, J.: Efficacy of dexmedetomidine in reducing post-operative pain and improving the quality of recovery in patients with burn wounds undergoing tangential excision skin grafting. Exp. Ther. Med. 17, 1776\u0026ndash;1782 (2019). https://doi.org/10.3892/etm.2019.7155\u003c/li\u003e\n\u003cli\u003eKim, S.Y., Kim, J.M., Lee, J.H., Song, B.M., Koo, B.N.: Efficacy of intraoperative dexmedetomidine infusion on emergence agitation and quality of recovery after nasal surgery. Br. J. Anaesth. 111, 222\u0026ndash;228 (2013). https://doi.org/10.1093/bja/aet056\u003c/li\u003e\n\u003cli\u003eLee, S. H., Lee, C. Y., Lee, J. G., Kim, N., Lee, H. M., Oh, Y. J.: Intraoperative dexmedetomidine improves the quality of recovery and postoperative pulmonary function in patients undergoing video-assisted thoracoscopic surgery: A CONSORT-prospective, randomized, controlled trial. Med. (Baltim.) 95, e2854 (2016). https://doi.org/10.1097/MD.0000000000002854\u003c/li\u003e\n\u003cli\u003eSherif, A.A., Elsersy, H.E.: The impact of dexmedetomidine or Xylocaine continuous infusion on opioid consumption and recovery after laparoscopic sleeve gastrectomy. Minerva Anestesiol. 83, 1274\u0026ndash;1282 (2017). https://doi.org/10.23736/S0375-9393.17.11855-9\u003c/li\u003e\n\u003cli\u003eZhang, L.Y., Zhang, Y.H., Shen, J., Luo, Y.: Effects of dexmedetomidine on post-operative recovery and mental status in patients receiving robotic-assisted thoracic surgery. Ann. Palliat. Med. 8, 469\u0026ndash;475 (2019). https://doi.org/10.21037/apm.2019.08.09\u003c/li\u003e\n\u003cli\u003eFlynn, B.C., Nemergut, E.C.: Postoperative nausea and vomiting and pain after transsphenoidal surgery: A review of 877 patients. Anesth. Analg. 103, 162\u0026ndash;167, table of contents (2006). https://doi.org/10.1213/01.ane.0000221185.08155.80\u003c/li\u003e\n\u003cli\u003eLabaf, A., Asghari, F., Samadi, S., Abdollahi, A., Zobeiry, S., Molavi, K.: Experiences of conscious patients undergoing tracheal intubation: A qualitative study. Arch. Anesthesiol. Crit. Care 8, 3\u0026ndash;10 (2022). https://doi.org/10.18502/aacc.v8i1.8237\u003c/li\u003e\n\u003cli\u003eArcangeli, A., D\u0026rsquo;Al\u0026ograve;, C., Gaspari, R.: Dexmedetomidine use in general anaesthesia. Curr. Drug Targets 10, 687\u0026ndash;695 (2009). https://doi.org/10.2174/138945009788982423\u003c/li\u003e\n\u003cli\u003eKaur, M., Singh, P.M.: Current role of dexmedetomidine in clinical anesthesia and intensive care. Anesth. Essays Res. 5, 128\u0026ndash;133 (2011). https://doi.org/10.4103/0259-1162.94750\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":"Dexmedetomidine, Nonfunctioning pituitary adenoma, Endoscopic transsphenoidal surgery, Quality of recovery","lastPublishedDoi":"10.21203/rs.3.rs-4149671/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4149671/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eIntraoperative dexmedetomidine administration attenuates surgical stress response and reduces postoperative pain, which are both essential for enhancing postoperative quality of recovery (QoR). This study aimed to determine whether intraoperative dexmedetomidine could improve early postoperative QoR in patients with nonfunctioning pituitary adenoma (NFPA) undergoing endoscopic transsphenoidal surgery (ETS).\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePatients with NFPA who underwent ETS under total intravenous anesthesia using continuous infusion of propofol and remifentanil were randomly assigned to receive either intraoperative dexmedetomidine (dexmedetomidine group, n\u0026thinsp;=\u0026thinsp;29) or normal saline (control group, n\u0026thinsp;=\u0026thinsp;32). The QoR-15 questionnaire was used to evaluate the postoperative QoR. The primary outcome measure was the QoR-15 score on postoperative day 1. Perioperative serum cortisol levels, intraoperative serum interleukin-6 levels, and pain scores at 4, 24, and 48 h postoperatively were also evaluated.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe QoR-15 score on postoperative day 1 did not differ between the dexmedetomidine and control groups (94.0 [79.0\u0026ndash;112.0] vs. 92.5 [68.3\u0026ndash;110.8], P\u0026thinsp;=\u0026thinsp;0.606). Perioperative serum cortisol levels showed no significant time \u0026times; group effect (P\u0026thinsp;=\u0026thinsp;0.578). Intraoperative serum interleukin-6 level did not differ between the two groups (P\u0026thinsp;=\u0026thinsp;0.974). Pain score was lower in the dexmedetomidine group at 4 h postoperatively (0.0 [0.0\u0026ndash;0.0] vs. 1.0 [0.0\u0026ndash;3.0], P\u0026thinsp;=\u0026thinsp;0.003) than the control group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eDexmedetomidine, as an anesthetic adjuvant, did not improve early postoperative QoR in patients with NFPA during ETS.\u003c/p\u003e","manuscriptTitle":"Effect of intraoperative dexmedetomidine on early postoperative quality of recovery in patients undergoing endoscopic transsphenoidal surgery for non-functioning pituitary adenoma: a randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-03-27 17:39:59","doi":"10.21203/rs.3.rs-4149671/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":"15f34574-34af-4dc7-8bdf-41f600b74f7b","owner":[],"postedDate":"March 27th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-03-28T09:35:16+00:00","versionOfRecord":[],"versionCreatedAt":"2024-03-27 17:39:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4149671","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4149671","identity":"rs-4149671","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}