Effect of Phenylephrine versus Ephedrine on Postoperative Delirium in Elderly Patients Undergoing Knee Arthroplasty General Anaesthesia：A Single-Center Trial

Effect of Phenylephrine versus Ephedrine on Postoperative Delirium in Elderly Patients Undergoing Knee Arthroplasty General Anaesthesia：A Single-Center 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 Article Effect of Phenylephrine versus Ephedrine on Postoperative Delirium in Elderly Patients Undergoing Knee Arthroplasty General Anaesthesia：A Single-Center Trial Changjian Zheng, Bin Wang, Jiuzhou Fu, Hui Peng, Yongquan Chen, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4499979/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jul, 2024 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Despite equalizing blood pressure(BP), ephedrine and phenylephrine exhibit distinct impacts on rSO2. However, whether this heterogeneity in rSO2 affects the occurrence of POD remains understudied. This study aimed to explore the effects of maintaining BP with ephedrine versus phenylephrine on the incidence of POD in elderly patients undergoing knee arthroplasty under general anesthesia. A total of 120 patients aged 60-90 years undergoing knee arthroplasty were included in this study.The patients were randomly divided into two groups: the ephedrine group and the phenylephrine group. After anesthesia induction, continuous infusion of the respective medication was initiated to maintain intraoperative mean arterial pressure within the normal range (baseline mean arterial pressure ± 20%).The primary outcome measures included the incidence of POD within 1-3 days after the surgery. The incidence of POD on the first day after surgery was lower in the ephedrine group compared to the phenylephrine group (33% vs 7%, P < 0.001 ). However, there was no significant difference in the incidence of POD between the two groups on the second and third postoperative days. During surgery, the ephedrine group exhibited significantly increased CO and rSO2 compared to the phenylephrine group (P < 0.05). Clinical Trials Registry: ChiCTR2200064849, principal investigator: Changjian Zheng. Health sciences/Medical research Health sciences/Signs and symptoms Figures Figure 1 Figure 2 Introduction Postoperative delirium (POD) is a frequent neurological complication in elderly patients after surgery. It is an acute onset and short-term brain dysfunction characterized by attention disorders, disordered levels of consciousness, changes in cognitive functions, and significant fluctuations [1 、 2] ，It typically manifests within three days following the procedure [ 3 , 4 ] . POD can result in prolonged recovery, exacerbation of complications, delayed discharge, increased hospital burden, and serves as an independent risk factor for higher rates of long-term postoperative cognitive dysfunction(POCD) and short-term mortality [ 5 , 6 ] . Cerebral perfusion and oxygenation imbalance is one of the most important causes of POD [7 、 8] , Phenylephrine and ephedrine are commonly used perioperative vasoactive drugs, However, this two drugs had different effects on cerebral oxygenation, with phenylephrine decreasing CO and rSO 2 in healthy patients, while remaining stable in the ephedrine group [9 、 10] , a systematic review found that the use of phenylephrine during anesthesia to treat intraoperative hypotension led to a sustained decrease in cerebral oxygen saturation and CO [11] , a more recent study found that ephedrine improves cerebral blood flow and oxygenation of brain tissues in patients with brain tumors, and that it was superior to phenylephrine in terms of improving cerebral macro- and micro-hemodynamics and oxygenation [12] . However, whether this heterogeneity has adverse clinical consequences in frail elderly patients has not been studied. In this investigation, we utilized these two drugs to manage intraoperative and examined their impact on the incidence of POD in elderly patients undergoing knee arthroplasty. Based on this, we hypothesized that the ephedrine group would exhibit higher rSO 2 and CO during surgery and correlates with lower incidence of POD Methods This randomized, double-blind, controlled study was conducted from October 2022 to July 2023 in accordance with the principles of the Helsinki Declaration. The study received approval from the Ethics Committee of the First Affiliated Hospital of Wannan Medical College, Wuhu, China [Approval No.: 2022 Ethics Research No. 46]. Prior to patient enrollment (ChiCTR2200064849), the trial was registered in the Chinese Clinical Trial Registry. All patients provided written informed consent, and randomization was performed by a statistician using a random number generator. Inclusion criteria: Patients aged 60–90 years undergoing knee arthroplasty, with an ASA classification ofⅠto Ⅲ, and a New York Heart Association functional classification of Ⅱ to Ⅲ. Exclusion criteria: Severe cardiac, pulmonary, hepatic, or renal dysfunction; a history of psychiatric illness or long-term use of psychotropic medications (dementia, schizophrenia); chronic use of analgesic medications; a positive Confusion Assessment Method (CAM) preoperatively; a score of ≥ 8 errors on the Short Portable Mental Status Questionnaire (SPMSQ) preoperatively, indicating severe cognitive impairment(MMSE < 27); diabetes patients with severe complications (diabetic ketoacidosis, hyperosmolar coma, various infections, large vessel disease, diabetic nephropathy), patients with severe infections; language communication barriers; inability to complete cognitive function tests. Randomization and Blinding Upon obtaining informed consent, a researcher randomly allocated the patients into two groups using a random number method. The anesthesiologist adjusted and intervened in intraoperative MAP based on each patient's baseline MAP. Both the outcome assessors, surgical team, Anesthetist were blinded to the group assignments of the participants. Perioperative Hemodynamic Management The patient's baseline MAP was determined as the average value of MAP measured at 10:00 am in the ward before the surgery. Non-invasive monitoring was conducted every 3 minutes during the surgery. After anesthesia induction, vasopressor drugs were continuously administered following the dosages reported in previous literature [ 29 , 30 ] . The ephedrine group received a continuous infusion of 5 mg/ml ephedrine, and the phenylephrine group received a continuous infusion of 0.1 mg/ml phenylephrine. Both groups were initially infused at a rate of 20 ml/h after anesthesia induction, and adjustments were made based on changes in . Intraoperative hypertension was defined as an MAP increase of more than 10–20% above the baseline value, resulting in a reduction of the infusion rate to 10 ml/h. If the MAP increased by more than 20% above the baseline value, the infusion of vasopressor drugs was halted. Intraoperative hypotension was defined as an MAP decrease of 10–20% below the baseline value, leading to an adjustment of the infusion rate to 40 ml/h. If the MAP decreased by more than 20% below the baseline value, a 6 mg bolus of ephedrine or 100 µg of phenylephrine was intravenously administered. In the case of bradycardia (defined as heart rate less than 50 beats/min), 0.5 mg atropine was administered. In the case of tachycardia (defined as heart rate greater than 100 beats/min), 20 mg esmolol was administered. Outcome measures The primary outcome measure of this study was the incidence of POD within 3 days after surgery. A professional assessor, who was unaware of the group allocation, evaluated the patients in the ward at noon each day after surgery using the Confusion Assessment Method (CAM). with a score of greater than 5 localized to the occurrence of agitation. Patients' rSO 2 , CO, MAP, HR were recorded at baseline (pre-anesthesia), 2 minutes after anesthesia induction (T1), 4 minutes after induction (T2), start of surgery (T3), 10 minutes into surgery (T4), 20 minutes (T5), 30 minutes (T6), 40 minutes (T7), 50 minutes (T8), 60 minutes (T9), and just before the end of surgery (T10) respectively. Additionally, data were collected on intraoperative anesthesia drug usage, surgical duration, PACU stay time, length of hospital stay, incidence of agitation, VAS pain scores, and postoperative complications. Sample Size Estimation The sample size for this study was determined using PASS 2008 (NCSS, LLC, Kaysville, Utah, USA) software, within the framework of a randomized controlled trial comprising two groups: the phenylephrine group and the ephedrine group, with POD as the primary outcome measure. Based on literature review, the anticipated incidence rates of POD were 22% for the phenylephrine group and 4% for the ephedrine group [ 31 ] . To achieve 80% confidence in detecting a true difference with a bilateral significance level (ɑ) of 0.05, the software calculated a requisite sample size of 108 participants across both groups. Considering a 20% dropout rate, We eventually included 130 patients in the group. Statistical Analysis The statistical analysis was conducted using SPSS version 22.0(SPSS Inc, Chicago, IL, USA). Continuous variables were assessed for normal distribution using the Kolmogorov-Smirnov test. Normally distributed data were presented as mean and standard deviation, while non-normally distributed data were presented as median (25%-75% pencentile). Categorical data were presented as frequency and percentage and analyzed using a two-tailed chi-square test or Fisher's exact test. For normally distributed groups, the t-test was utilized, and for non-normally distributed groups, the Mann-Whitney U test was employed. To compare continuous variables (MAP, HR, rSO 2 , CO) between the two groups at different time points, repeated measurements One-way ANOVA of variance was performed. A p-value of less than 0.05 was considered statistically significant. Results The CONSORT diagram in Fig. 1 illustrates the patient flow throughout the study. Initially, 150 patients screened for inclusion, but 20 were excluded for various reasons, such as refusal to sign informed consent, surgery cancellation, change in anesthesia method, or other reasons. After discharge, 4 patients were lost to follow-up, and 6 patients declined further evaluation, resulting in a final inclusion of 120 patients, with 60 in each group (phenylephrine and ephedrine). Baseline Characteristics : Table 1 displays the baseline characteristics, showing no statistically significant differences between the two groups in terms of gender, age, body mass index, ASA classification, smoking status, alcohol consumption, surgical history, comorbidities, and preoperative hemoglobin levels. Additionally, no significant differences were observed in intraoperative anesthesia drug usage, surgical duration, post-anesthesia care unit (PACU) stay time, baseline MAP, HR, rSO 2 , CO, blood loss, or urine output between the two groups (Table 2). Primary Outcome Measures : The incidence of POD on the first postoperative day was significantly lower in the ephedrine group compared to the phenylephrine group [20 (33) vs. 4 (7), P < 0.001]. However, there were no significant differences in POD incidence between the two groups on the second postoperative day [4 (7) vs. 2 (3), P = 0.412] and the third postoperative day [1 (2) vs. 0, P = 0.315] (Table 4). Secondary Outcome Measures : Comparing the changes in MAP, HR, CO, and rSO 2 after anesthesia induction (Table 2, Fig. 2), the phenylephrine group exhibited a decrease in rSO 2 (-8.4 ± 0.6%), while the ephedrine group showed a milder decrease (-1.3 ± 0.6%). Changes of rSO 2 between two groups was 7.2% (95% CI: 6.0, 8.3; P < 0.001; Table 2, Fig. 2). Additionally, the phenylephrine group showed a decrease in CO (-0.40 ± 0.06 L/min), while the ephedrine group experienced an increase in CO during surgery (0.45 ± 0.06 L/min). Changes of CO between two groups was 0.85 L/min, which was statistically significant (95% CI: 0.69, 1.00; P < 0.001; Table 2, Fig. 2). Both groups had transient decreases in MAP during surgery, but overall changes were stable, with no statistically difference between the groups (95% CI: 1.63, 3.23; P = 0.517; Table 2, Fig. 2). Furthermore, the phenylephrine group showed a significant decrease in HR (−12 ± 1 beats/min), while the ephedrine group showed a increase in HR (10 ± 1 beats/min). The difference in HR between the two groups was 22 beats/min and was statistically significant (95% CI: 19.5, 25.1; P < 0.001; Table 2, Fig. 2). Postoperative Complications : On the first postoperative day, there were 9 cases of nausea and vomiting in the phenylephrine group, compared to 3 cases in the ephedrine group ( P = 0.068). Although there were no statistically significant differences in postoperative visual analogue scale (VAS) pain scores and between the groups, 14 patients in the phenylephrine group experienced emergence agitation in the PACU, compared to 4 patients in the ephedrine group, which was statistically significant ( P = 0.011). No other statistically significant differences were observed in terms of cardiovascular and neurological complications between the groups ( Table 3). Discussion This study found that ephedrine's CO was increased when maintaining intraoperative, whereas phenylephrine exhibited a decrease in CO, which is consistent with the results of some previous studies. A study on prophylactic phenylephrine infusion during spinal anesthesia demonstrated decreased CO and cerebral oxygen saturation at various time points [ 13 ] , Another study comparing ephedrine and phenylephrine revealed that phenylephrine decreased CO, whereas ephedrine maintained it [ 14 ] . In turn, a significant correlation was observed between rSO 2 and CO. Reduced CO may trigger compensatory increases in cerebral oxygen uptake, leading to a decrease in mean frontal lobe rSO 2 [ 12 ] . One possible mechanism is that CO indirectly causes changes in rSO 2 by affecting cerebral perfusion [ 15 ] , we all know that cerebral oxygenation depends on the delivery of oxygen to the brain and cerebral oxygen consumption (CMRO 2 ), which relies on cerebral blood flow (CBF) and arterial oxygen content. Studies have demonstrated that if CMRO 2 and arterial oxygen content remain constant, changes in rSO 2 correlate with changes in CBF [ 16 ] . In our study, patients received general anesthesia with relatively consistent doses and depth. Hence, CMRO 2 can be approximated as constant, and variations in CO directly impact CBF. Therefore, the observed changes in rSO 2 may be partly attributed to indirect CBF fluctuations due to changes in CO. In addition, we know that the rapid increase in arterial pressure induced by phenylephrine can lead to increased sympathetic nerve activity in the carotid ganglia [17、18] , and the small arteries in the brain are mainly innervated by sympathetic nerve fibers [ 19 ] . Therefore, the phenylephrine-induced enhancement of sympathetic nerve activity leads indirectly to cerebral vasoconstriction and may be related to the decrease in rSO 2 in the present study [17、18] . The decrease in rSO 2 in our study was significantly correlated with the incidence of POD, which is consistent with previous studies that patients undergoing cardiac [ 20 ] and orthopedic [ 21 ] surgeries have revealed a dose-response relationship between cerebral oxygen saturation and postoperative neurocognitive disorders. Moreover, a recent large retrospective study indirectly supports this hypothesis, demonstrating that low peripheral oxygen saturation (closely linked to cerebral oxygen saturation) and low carbon dioxide levels (directly reflecting cerebral perfusion) elevate the risk of POD [ 8 ] . Wang et al. established a significant correlation between rSO 2 and hypotension, leading to profound delirium [ 22 ] . Although our study found a slight decrease in rSO 2 in the ephedrine group as well, We consider that such small fluctuations in rSO 2 are not yet sufficient to alter clinical outcomes. On the other hand, the two drugs do have significant heterogeneity in their effects on cerebral circulation, especially since this study focused on vulnerable populations that may be more susceptible. Similar studies have illustrated that the effects of vasoactive drugs on vulnerable populations may be more pronounced and thus have a profound impact on clinical outcomes. A recent MRI-based study analyzed patients with brain tumors who received ephedrine or phenylephrine to achieve similar MAP endpoints. The results demonstrated that the ephedrine group exhibited higher cerebral blood flow and cerebral tissue oxygenation indices compared to the phenylephrine group. Additionally, the study revealed that phenylephrine disrupted microcirculation, resulting in reduced oxygen extraction, while ephedrine improved both macro- and microcirculation in the brain, enhancing oxygen extraction [ 14 ] . Previous reports have indicated that phenylephrine treatment in patients with septic shock can reduce HR, impair hepatic and renal perfusion, and compromise kidney function [ 23 , 24 ] . In summary, this study reveals the different effects of ephedrine and phenylephrine on the incidence of POD in fragile elderly patients undergoing knee arthroplasty, where ephedrine can be associated with a reduction in the incidence of POD and may be related to perioperative changes in CO and rSO 2 , This study also has some limitations. First, this study was a single-center, small-sample study, multicenter, large-sample studies are still needed to further clarify the different roles of the drugs. Second, some patients in the phenylephrine group of this study used a single dose of atropine intraoperatively, and although the timing of the atropine administration and dosage were different from those in previous studies [25、26] , The interference of atropine on the results cannot be absolutely ruled out, and thirdly, in this study, intraoperative CO and rSO 2 changes were monitored by using Vigileo monitor and near-infrared spectroscopy, but there is still a possibility that imprecise monitoring and extracranial contamination may have interfered with the values [27、28] . Abbreviations POD Postoperative delirium POCD Postoperative cognitive dysfunction CO Cardiac output rSO 2 Regional cerebral oxygen saturation VAS Visual analogue scale PACU Post-anesthesia care unit CAM Confusion Assessment Method ASA American society of Aneshesiologists CMRO 2 Cerebral oxygen consumption CBF Cerebral blood flow BIS bispectral index Declarations Acknowledgements We deeply thank our colleagues at the Department of Anesthesiology, Yijishan Hospital of Wannan Medical College, for assistance with the samples. Author contributions : Changjian Zheng: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Writing - original draf. Xian Wen Hu, Bin Wang: Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Resources, Supervision, Writing - review & editing.Hui Peng: Formal analysis, Validation.Xian Wen Hu: Methodology, Resources.Yongquan Chen: Methodology, Resources, Validation. Jiuzhou Fu: Investigation. Funding: Major Research Project of Anhui Provincial Department of Education (KJ2021ZD0030), Key Technologies Research and Development Program of Anhui Province (2022e07020045), Key Projects of Clinical Cultivation Program of the Second Affiliated Hospital of Anhui Medical University (2021LCZD02) Competing interests The authors declare no competing interests. Declaration section As this paper is only part of a series of trials, we have further related trials to conduct, and the data sets generated and/or analyzed during the current study are not publicly available but are available from the corresponding authors at their reasonable request. References Inouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet 2014; 383: 911–22 Wu WF, Lin JT, Qiu YK, Dong W, Wan J, Li S, Zheng H, Wu YQ. The role of epigenetic modification in postoperative cognitive dysfunction. Ageing Res Rev. 2023;89:101983. Zhao B, Ni Y, Tian X. Low plasma cholinesterase activity is associated with postoperative delirium after noncardiac surgery in elderly patients: a prospective observational study. Psychosomatics 2019;60(2):190–6 Yang Y, Zhao X, Dong T, Yang Z, Zhang Q, Zhang Y. Risk factors for postoperative delirium following hip fracture repair in elderly patients: a systematic review and meta-analysis. Aging Clin Exp Res. 2017;29(2):115–126. Witlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010;304(4):443–51. Jin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth. 2020;125(4):492–504. Lu Y, Di M, Li C, Chen M, Yuan K, Shangguan W. Comparing the response of pulse oximetry and regional cerebral oxygen saturation to hypoxia in preschool children. Exp Ther Med. 2020;19(1):353–358. Ahrens E, Tartler TM, Suleiman A, Wachtendorf LJ, Ma H, Chen G, Kendale SM, Kienbaum P, Subramaniam B, Wagner S, Schaefer MS. Dose-dependent relationship between intra-procedural hypoxaemia or hypocapnia and postoperative delirium in older patients. Br J Anaesth. 2023;130(2):e298-e306. Meng L, Cannesson M, Alexander BS, Yu Z, Kain ZN, Cerussi AE, Tromberg BJ, Mantulin WW. Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients. Br J Anaesth. 2011;107(2):209–17. Foss VT, Christensen R, Rokamp KZ, Nissen P, Secher NH, Nielsen HB. Effect of phenylephrine vs. ephedrine on frontal lobe oxygenation during caesarean section with spinal anesthesia: an open label randomized controlled trial. Front Physiol. 2014;5:81. Larson S, Anderson L, Thomson S. Effect of phenylephrine on cerebral oxygen saturation and cardiac output in adults when used to treat intraoperative hypotension: a systematic review. JBI Evid Synth. 2021;19(1):34–58. Koch KU, Mikkelsen IK, Espelund US, Angleys H, Tietze A, Oettingen GV, Juul N, Østergaard L, Rasmussen M. Cerebral Macro- and Microcirculation during Ephedrine versus Phenylephrine Treatment in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial Using Magnetic Resonance Imaging. Anesthesiology. 2021;135(5):788–803. Orbach-Zinger S, Bizman I, Firman S, Lev S, Gat R, Ashwal E, Vaturi M, Razinski E, Davis A, Shmueli A, Eidelman LA. Perioperative noninvasive cardiac output monitoring in parturients undergoing cesarean delivery with spinal anesthesia and prophylactic phenylephrine drip: a prospective observational cohort study. J Matern Fetal Neonatal Med. 2019;32(19):3153–3159. Meng L, Hou W, Chui J, Han R, Gelb AW. Cardiac Output and Cerebral Blood Flow: The Integrated Regulation of Brain Perfusion in Adult Humans. Anesthesiology. 2015;123(5):1198–208. Wong FY, Nakamura M, Alexiou T, Brodecky V, Walker AM. Tissue oxygenation index measured using spatially resolved spectroscopy correlates with changes in cerebral blood flow in newborn lambs. Intensive Care Med. 2009;35(8):1464–70. Wong FY, Nakamura M, Alexiou T, Brodecky V, Walker AM. Tissue oxygenation index measured using spatially resolved spectroscopy correlates with changes in cerebral blood flow in newborn lambs. Intensive Care Med. 2009;35(8):1464–70. Cassaglia PA, Griffifiths RI, Walker AM. Sympathetic nerve activity in the superior cervical ganglia increases in response to imposed increases in arterial pressure. Am J Physiol Regul Integr Comp Physiol 2008; 294: R1255–61 Cassaglia PA, Griffifiths RI, Walker AM. Cerebral sympathetic nerve activity has a major regulatory role in the cerebral circulation in REM sleep. J Appl Physiol 2009; 106: 1050–6 Hamel E. Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol 2006; 100: 1059–64 Slater JP, Guarino T, Stack J, Vinod K, Bustami RT, Brown JM 3rd, Rodriguez AL, Magovern CJ, Zaubler T, Freundlich K, Parr GV. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg. 2009;87(1):36–44; discussion 44 – 5. Kim J, Shim JK, Song JW, Kim EK, Kwak YL. Postoperative Cognitive Dysfunction and the Change of Regional Cerebral Oxygen Saturation in Elderly Patients Undergoing Spinal Surgery. Anesth Analg. 2016;123(2):436–44. Wang X, Feng K, Liu H, Liu Y, Ye M, Zhao G, Wang T. Regional cerebral oxygen saturation and postoperative delirium in endovascular surgery: a prospective cohort study. Trials. 2019;20(1):504. Morelli A, Lange M, Ertmer C, Dünser M, Rehberg S, Bachetoni A, D'Alessandro M, Van Aken H, Guarracino F, Pietropaoli P, Traber DL, Westphal M. Short-term effects of phenylephrine on systemic and regional hemodynamics in patients with septic shock: a crossover pilot study. Shock. 2008;29(4):446–51. Reinelt H, Radermacher P, Kiefer P, Fischer G, Wachter U, Vogt J, Georgieff M. Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med. 1999;27(2):325–31. Ferré F, Piel-Julian ML, Tincres F, Ba C, Menut R, Ferrier A, Bosch L, Martin C, Labaste F, Montastruc F, Sommet A, Balardy L, Minville V. A High Postoperative Atropinic Burden is Associated with Postoperative Delirium in Elderly Patients with Hip Fracture: Results of the Prospective, Observational, ATROPAGE Trial. Clin Interv Aging. 2022;17:1931–1938. Klamer TT, Wauters M, Azermai M, Durán C, Christiaens T, Elseviers M, Vander Stichele R. A Novel Scale Linking Potency and Dosage to Estimate Anticholinergic Exposure in Older Adults: the Muscarinic Acetylcholinergic Receptor ANTagonist Exposure Scale. Basic Clin Pharmacol Toxicol. 2017;120(6):582–590. Argueta E, Berdine G, Pena C, Nugent KM. FloTrac® monitoring system: what are its uses in critically ill medical patients? Am J Med Sci. 2015;349(4):352–6. Kubo Y, Kubo T, Toki T, Yokota I, Morimoto Y. Effects of ephedrine and phenylephrine on cerebral oxygenation: observational prospective study using near-infrared time-resolved spectroscopy. J Clin Monit Comput. 2023;37(5):1171–1177. Das S, Mukhopadhyay S, Mandal M, Mandal S, Basu SR. A comparative study of infusions of phenylephrine, ephedrine and phenylephrine plus ephedrine on maternal haemodynamics in elective caesarean section. Indian J Anaesth. 2011;55(6):578–83. Ngan Kee WD, Lee A, Khaw KS, Ng FF, Karmakar MK, Gin T. A randomized double-blinded comparison of phenylephrine and ephedrine infusion combinations to maintain blood pressure during spinal anesthesia for cesarean delivery: the effects on fetal acid-base status and hemodynamic control. Anesth Analg. 2008;107(4):1295–302. Xu X, Hu X, Wu Y, Li Y, Zhang Y, Zhang M, Yang Q. Effects of different BP management strategies on postoperative delirium in elderly patients undergoing hip replacement: A single center randomized controlled trial. J Clin Anesth. 2020;62:109730. Tables Table 1 Demographic and Clinical Characteristics at Baseline Demographics Phenylephrine (n=60) Ephedrine (n=60) P value Sex, n(%) Male Age, yr BMI, kg.m -2 ASA, n(%) Ⅰ Ⅱ Ⅲ Smoking, n(%) Alcohol abuse, n(%) Surgical history, n(%) Comorbid disease by System Cardiovascular, n(%) Gastrointestinal, n(%) Urinary tract, n(%) Central nervous system, n(%) Respiratory, n(%) Preoperative Hb, median (IQR)g/L 15 (25) 69±4 23±3 2（3） 47（78） 11（18） 18(30) 12(20) 7(12) 36(60) 15(25) 13(22) 8(13) 6(10) 119(78-149) 14 (23) 68±5 22±3 3（5） 44（73） 13（22） 15(25) 14(23) 6(10) 31(52) 20(33) 10(17) 9(15) 9(15) 123(83-146) 0.813 0.248 0.128 0.792 0.540 0.658 0.769 0.358 0.315 0.487 0.793 0.408 0.629 ASA:American Society of Anesthesiologists; BMI:body mass index; Hb:hemoglobin The data are presented as means±standard deviation for continous variables and frequency(%) for categorical variables, Data that are not normally distributed are represented by the median (interquartile) Table 2 Intraoperative Characteristics of Patients Undergoing Surgery Characteristic Phenylephrine (n=60) Ephedrine (n=60) P value Duration of Surgery, min PACU residence time, min Anaesthetic，median(IQR) Propofol, mg Remifentanil, ug Sufentanil, ug Rocuronium, mg Monitoring Baseline MAP , mmHg HR, median(IQR), beats/min rSO 2, % CO, median(IQR), L/min Hemodynamic changes Change in MAP, mmHg Change in HR,beats/min Change in rSO 2, % Change in CO, L/min Blood loss, median(IQR), ml Urine volum, median(IQR), ml Length of hospital stay, median(IQR), days 97±14 32±8 750(680-828) 1515±384 35(31-45) 46(43-49) 93±9 80(75-86) 68±4 4.6(3.9-5.2) -8.6±0.9 -12±1 −8.4±0.6 -0.4±0.06 180(150-219) 172(156-194) 9(7-10) 102±16 31±9 783(682-868) 1537(1285-1800) 35(30-40) 46(43-51) 95±9 79(70-85) 67±5 4.3(3.7-5.0) -9.4±0.9 10±1 -1.3±0.6 0.45±0.06 190(170-250) 170(145-218) 8(7-10) 0.096 0.724 0.227 0.659 0.206 0.477 0.225 0.351 0.198 0.122 0.517 <0.001 <0.001 <0.001 0.089 0.966 0.286 PACU:Post anesthesia care unit; MAP:Mean arterial pressure; HR:Heart rate; rSO 2 :Regional cerebral oxygen; CO:Cardiac output The data are presented as means±standard deviation for continous variables, Non-normal distribution using median (interquartile) Table 3 Side Effects Between the two Groups Side effects Phenylephrine (n=60) Ephedrine (n=60) P value Nausea/vomiting,n(%) Postoperative day 1 Postoperative day 2 VAS Score Postoperative day 1 Postoperative day 2 Blood pressure,median(IQR),mmHg Postoperative day 1 Postoperative day 2 Neurological System Emergence agitation Headache and dizziness Stroke Cardiovascular System (PACU) Hypotension Hypertension Bradycardia 9(15) 2(3) 4.0(2.3-4.0) 2.0(1.3-3.0) 93±9 91±10 14（23） 1（2） 1（2） 4（7） 3（5） 2（3） 3(5) 1(2) 3.0(2.0-4.0) 2.0(1.0-3.0) 93±10 90±11 4*（7） 0 0 4（7） 1（2） 1（2） 0.068 0.559 0.120 0.531 0.809 0.575 0.011 0.315 0.315 1 0.309 0.559 VAS:Visual Analogue Scale, PACU:Post anesthesia care unit. The data are presented as means±standard deviation for continous variables and frequency(%) for categorical variables, Data that are not normally distributed are represented by the median (interquartile) Table 4 Incidence of POD Phenylephrine (n=60) Ephedrine (n=60) P value Postoperative day1 Postoperative day2 Postoperative day3 20(33) 4(7) 1(2) 4(7) 2(3) 0 <0.001 0.402 0.315 POD:Postoperative delirium Noncontinuous variables are presented as number of subjects (percentage). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4499979","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":313675845,"identity":"ba62e437-f7c3-4c9b-8881-c31fe7d84757","order_by":0,"name":"Changjian Zheng","email":"","orcid":"","institution":"The First Affiliated Hospital of Wannan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Changjian","middleName":"","lastName":"Zheng","suffix":""},{"id":313675846,"identity":"6e47cc13-888b-4bb5-bfa3-e5e143b066a7","order_by":1,"name":"Bin Wang","email":"","orcid":"","institution":"The First Affiliated Hospital of Wannan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Bin","middleName":"","lastName":"Wang","suffix":""},{"id":313675848,"identity":"764bf743-21fa-47a0-80d9-ac2aadc45dc4","order_by":2,"name":"Jiuzhou Fu","email":"","orcid":"","institution":"The First Affiliated Hospital of Wannan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Jiuzhou","middleName":"","lastName":"Fu","suffix":""},{"id":313675850,"identity":"a8e3268e-34c2-4f4c-ab6a-a12cf0cce252","order_by":3,"name":"Hui Peng","email":"","orcid":"","institution":"The First Affiliated Hospital of Wannan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Hui","middleName":"","lastName":"Peng","suffix":""},{"id":313675851,"identity":"83fa0778-dd18-4057-8f0c-f970db7d6c99","order_by":4,"name":"Yongquan Chen","email":"","orcid":"","institution":"The First Affiliated Hospital of Wannan Medical College","correspondingAuthor":false,"prefix":"","firstName":"Yongquan","middleName":"","lastName":"Chen","suffix":""},{"id":313675853,"identity":"33528a49-e437-4eb7-a2c7-12ce2d09f602","order_by":5,"name":"Xianwen Hu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYBACAyA+AGYxMzYc+GBgY0eCFvbmgwdnFKQlE6UFAniOJR/m+XCIsYGQFnOJHMMDP3cclgMyDA7bGBxgZmA/fHQDPi2WM9ISDvaeOWxsOQOoJcfgDh8DT1raDbwOu5F84ABv2+3EDTfAWp4xM0jwmBHQkthw8G/b7XqwFguDw4wNhLUkHzgMtCXB4MyxhMMMRGk58yzhsGzbf8MNx5sPHOwxSEtmI+iX4znGH9+2pckDzW/+8OOPjR0/++FjeLVgAjbSlI+CUTAKRsEowAYAPpBXtCafvxcAAAAASUVORK5CYII=","orcid":"","institution":"The Second Hospital of Anhui Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xianwen","middleName":"","lastName":"Hu","suffix":""}],"badges":[],"createdAt":"2024-05-30 03:08:29","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4499979/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4499979/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-024-68273-2","type":"published","date":"2024-07-27T16:16:06+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":58316800,"identity":"9deec189-2540-4344-9acd-fde72c5c8237","added_by":"auto","created_at":"2024-06-13 21:09:52","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":200915,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"Figures1.png","url":"https://assets-eu.researchsquare.com/files/rs-4499979/v1/6d68a49a4ce88e74f87eb8c8.png"},{"id":58316801,"identity":"1463af05-b1ed-4e3a-82af-6d1fe7d554ce","added_by":"auto","created_at":"2024-06-13 21:09:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":356172,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"Figures2.png","url":"https://assets-eu.researchsquare.com/files/rs-4499979/v1/fb1a1d7579bf82d822d3e333.png"},{"id":61596137,"identity":"c5c3f38c-e91a-4dd9-96bc-e8a3357e49b2","added_by":"auto","created_at":"2024-08-01 17:25:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1009437,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4499979/v1/dc9ea7f2-2a78-4ca9-acbb-a1c83bdc144b.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effect of Phenylephrine versus Ephedrine on Postoperative Delirium in Elderly Patients Undergoing Knee Arthroplasty General Anaesthesia：A Single-Center Trial","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePostoperative delirium (POD) is a frequent neurological complication \u0026nbsp;in elderly patients after surgery. It is an acute onset and short-term brain dysfunction characterized by attention disorders, disordered levels of consciousness, changes in cognitive functions, and significant fluctuations\u003csup\u003e[1\u003c/sup\u003e\u003csup\u003e、\u003c/sup\u003e\u003csup\u003e2]\u003c/sup\u003e，It typically manifests within three days following the procedure \u003csup\u003e[\u003c/sup\u003e\u003csup\u003e3\u003c/sup\u003e\u003csup\u003e,\u0026nbsp;\u003c/sup\u003e\u003csup\u003e4\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e. POD can result in prolonged recovery, exacerbation of complications, delayed discharge, increased hospital burden, and serves as an independent risk factor for higher rates of long-term postoperative cognitive dysfunction(POCD)\u0026nbsp;and short-term mortality\u003csup\u003e\u0026nbsp;[\u003c/sup\u003e\u003csup\u003e5\u003c/sup\u003e\u003csup\u003e,\u0026nbsp;\u003c/sup\u003e\u003csup\u003e6\u003c/sup\u003e\u003csup\u003e]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eCerebral perfusion and oxygenation imbalance is one of the most important causes of POD\u003csup\u003e[7\u003c/sup\u003e\u003csup\u003e、\u003c/sup\u003e\u003csup\u003e8]\u003c/sup\u003e, Phenylephrine and ephedrine are commonly used perioperative vasoactive drugs,\u0026nbsp;However,\u0026nbsp;this\u0026nbsp;two\u0026nbsp;drugs\u0026nbsp;had different effects on cerebral oxygenation, with phenylephrine decreasing CO and rSO\u003csub\u003e2\u003c/sub\u003e in healthy patients, while remaining stable in the ephedrine group\u003csup\u003e[9\u003c/sup\u003e\u003csup\u003e、\u003c/sup\u003e\u003csup\u003e10]\u003c/sup\u003e, a systematic review found that the use of phenylephrine during anesthesia to treat intraoperative hypotension led to a sustained decrease in cerebral oxygen saturation and\u0026nbsp;CO\u003csup\u003e[11]\u003c/sup\u003e, a more recent study found that ephedrine improves cerebral blood flow and oxygenation of brain tissues in patients with brain tumors, and that it was superior to phenylephrine in terms of improving cerebral macro- and micro-hemodynamics and oxygenation\u003csup\u003e[12]\u003c/sup\u003e.\u0026nbsp;However, whether this heterogeneity has adverse clinical consequences in frail elderly patients has not been studied.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn this investigation, we utilized these two drugs to manage intraoperative \u0026nbsp;and examined their impact on the incidence of POD in elderly patients undergoing \u0026nbsp;knee arthroplasty. Based on this, we hypothesized that the ephedrine group would exhibit higher rSO\u003csub\u003e2\u003c/sub\u003e and CO during surgery and correlates with lower incidence of POD\u0026nbsp;\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis randomized, double-blind, controlled study was conducted from October 2022 to July 2023 in accordance with the principles of the Helsinki Declaration. The study received approval from the Ethics Committee of the First Affiliated Hospital of Wannan Medical College, Wuhu, China [Approval No.: 2022 Ethics Research No. 46]. Prior to patient enrollment (ChiCTR2200064849), the trial was registered in the Chinese Clinical Trial Registry. All patients provided written informed consent, and randomization was performed by a statistician using a random number generator.\u003c/p\u003e\u003cp\u003eInclusion criteria: Patients aged 60–90 years undergoing knee arthroplasty, with an ASA classification ofⅠto Ⅲ, and a New York Heart Association functional classification of Ⅱ to Ⅲ.\u003c/p\u003e\u003cp\u003eExclusion criteria: Severe cardiac, pulmonary, hepatic, or renal dysfunction; a history of psychiatric illness or long-term use of psychotropic medications (dementia, schizophrenia); chronic use of analgesic medications; a positive Confusion Assessment Method (CAM) preoperatively; a score of ≥ 8 errors on the Short Portable Mental Status Questionnaire (SPMSQ) preoperatively, indicating severe cognitive impairment(MMSE \u0026lt; 27); diabetes patients with severe complications (diabetic ketoacidosis, hyperosmolar coma, various infections, large vessel disease, diabetic nephropathy), patients with severe infections; language communication barriers; inability to complete cognitive function tests.\u003c/p\u003e\u003cp\u003e\u003cb\u003eRandomization and Blinding\u003c/b\u003e\u003c/p\u003e\u003cp\u003eUpon obtaining informed consent, a researcher randomly allocated the patients into two groups using a random number method. The anesthesiologist adjusted and intervened in intraoperative MAP based on each patient's baseline MAP. Both the outcome assessors, surgical team, Anesthetist were blinded to the group assignments of the participants.\u003c/p\u003e\u003cp\u003e\u003cb\u003ePerioperative Hemodynamic Management\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe patient's baseline MAP was determined as the average value of MAP measured at 10:00 am in the ward before the surgery. Non-invasive monitoring was conducted every 3 minutes during the surgery. After anesthesia induction, vasopressor drugs were continuously administered following the dosages reported in previous literature \u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. The ephedrine group received a continuous infusion of 5 mg/ml ephedrine, and the phenylephrine group received a continuous infusion of 0.1 mg/ml phenylephrine. Both groups were initially infused at a rate of 20 ml/h after anesthesia induction, and adjustments were made based on changes in .\u003c/p\u003e\u003cp\u003eIntraoperative hypertension was defined as an MAP increase of more than 10–20% above the baseline value, resulting in a reduction of the infusion rate to 10 ml/h. If the MAP increased by more than 20% above the baseline value, the infusion of vasopressor drugs was halted. Intraoperative hypotension was defined as an MAP decrease of 10–20% below the baseline value, leading to an adjustment of the infusion rate to 40 ml/h. If the MAP decreased by more than 20% below the baseline value, a 6 mg bolus of ephedrine or 100 µg of phenylephrine was intravenously administered. In the case of bradycardia (defined as heart rate less than 50 beats/min), 0.5 mg atropine was administered. In the case of tachycardia (defined as heart rate greater than 100 beats/min), 20 mg esmolol was administered.\u003c/p\u003e\u003cp\u003e\u003cb\u003eOutcome measures\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe primary outcome measure of this study was the incidence of POD within 3 days after surgery. A professional assessor, who was unaware of the group allocation, evaluated the patients in the ward at noon each day after surgery using the Confusion Assessment Method (CAM). with a score of greater than 5 localized to the occurrence of agitation. Patients' rSO\u003csub\u003e2\u003c/sub\u003e, CO, MAP, HR were recorded at baseline (pre-anesthesia), 2 minutes after anesthesia induction (T1), 4 minutes after induction (T2), start of surgery (T3), 10 minutes into surgery (T4), 20 minutes (T5), 30 minutes (T6), 40 minutes (T7), 50 minutes (T8), 60 minutes (T9), and just before the end of surgery (T10) respectively. Additionally, data were collected on intraoperative anesthesia drug usage, surgical duration, PACU stay time, length of hospital stay, incidence of agitation, VAS pain scores, and postoperative complications.\u003c/p\u003e\u003cp\u003e\u003cb\u003eSample Size Estimation\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe sample size for this study was determined using PASS 2008 (NCSS, LLC, Kaysville, Utah, USA) software, within the framework of a randomized controlled trial comprising two groups: the phenylephrine group and the ephedrine group, with POD as the primary outcome measure. Based on literature review, the anticipated incidence rates of POD were 22% for the phenylephrine group and 4% for the ephedrine group\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e. To achieve 80% confidence in detecting a true difference with a bilateral significance level (ɑ) of 0.05, the software calculated a requisite sample size of 108 participants across both groups. Considering a 20% dropout rate, We eventually included 130 patients in the group.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStatistical Analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe statistical analysis was conducted using SPSS version 22.0(SPSS Inc, Chicago, IL, USA). Continuous variables were assessed for normal distribution using the Kolmogorov-Smirnov test. Normally distributed data were presented as mean and standard deviation, while non-normally distributed data were presented as median (25%-75% pencentile). Categorical data were presented as frequency and percentage and analyzed using a two-tailed chi-square test or Fisher's exact test. For normally distributed groups, the t-test was utilized, and for non-normally distributed groups, the Mann-Whitney U test was employed. To compare continuous variables (MAP, HR, rSO\u003csub\u003e2\u003c/sub\u003e, CO) between the two groups at different time points, repeated measurements One-way ANOVA of variance was performed. A p-value of less than 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe CONSORT diagram in Fig.\u0026nbsp;1 illustrates the patient flow throughout the study. Initially, 150 patients screened for inclusion, but 20 were excluded for various reasons, such as refusal to sign informed consent, surgery cancellation, change in anesthesia method, or other reasons. After discharge, 4 patients were lost to follow-up, and 6 patients declined further evaluation, resulting in a final inclusion of 120 patients, with 60 in each group (phenylephrine and ephedrine).\u003c/p\u003e\u003cp\u003e\u003cb\u003eBaseline Characteristics\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eTable\u0026nbsp;1 displays the baseline characteristics, showing no statistically significant differences between the two groups in terms of gender, age, body mass index, ASA classification, smoking status, alcohol consumption, surgical history, comorbidities, and preoperative hemoglobin levels. Additionally, no significant differences were observed in intraoperative anesthesia drug usage, surgical duration, post-anesthesia care unit (PACU) stay time, baseline MAP, HR, rSO\u003csub\u003e2\u003c/sub\u003e, CO, blood loss, or urine output between the two groups (Table\u0026nbsp;2).\u003c/p\u003e\u003cp\u003e\u003cb\u003ePrimary Outcome Measures\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eThe incidence of POD on the first postoperative day was significantly lower in the ephedrine group compared to the phenylephrine group [20 (33) vs. 4 (7), \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001]. However, there were no significant differences in POD incidence between the two groups on the second postoperative day [4 (7) vs. 2 (3), \u003cem\u003eP\u003c/em\u003e = 0.412] and the third postoperative day [1 (2) vs. 0, \u003cem\u003eP\u003c/em\u003e = 0.315] (Table\u0026nbsp;4).\u003c/p\u003e\u003cp\u003e\u003cb\u003eSecondary Outcome Measures\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eComparing the changes in MAP, HR, CO, and rSO\u003csub\u003e2\u003c/sub\u003e after anesthesia induction (Table\u0026nbsp;2, Fig.\u0026nbsp;2), the phenylephrine group exhibited a decrease in rSO\u003csub\u003e2\u003c/sub\u003e (-8.4 ± 0.6%), while the ephedrine group showed a milder decrease (-1.3 ± 0.6%). Changes of rSO\u003csub\u003e2\u003c/sub\u003e between two groups was 7.2% (95% CI: 6.0, 8.3; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001; Table\u0026nbsp;2, Fig.\u0026nbsp;2). Additionally, the phenylephrine group showed a decrease in CO (-0.40 ± 0.06 L/min), while the ephedrine group experienced an increase in CO during surgery (0.45 ± 0.06 L/min). Changes of CO between two groups was 0.85 L/min, which was statistically significant (95% CI: 0.69, 1.00; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001; Table\u0026nbsp;2, Fig.\u0026nbsp;2). Both groups had transient decreases in MAP during surgery, but overall changes were stable, with no statistically difference between the groups (95% CI: 1.63, 3.23; \u003cem\u003eP\u003c/em\u003e = 0.517; Table\u0026nbsp;2, Fig.\u0026nbsp;2). Furthermore, the phenylephrine group showed a significant decrease in HR (−12 ± 1 beats/min), while the ephedrine group showed a increase in HR (10 ± 1 beats/min). The difference in HR between the two groups was 22 beats/min and was statistically significant (95% CI: 19.5, 25.1; \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001; Table\u0026nbsp;2, Fig.\u0026nbsp;2).\u003c/p\u003e\u003cp\u003e\u003cb\u003ePostoperative Complications\u003c/b\u003e:\u003c/p\u003e\u003cp\u003eOn the first postoperative day, there were 9 cases of nausea and vomiting in the phenylephrine group, compared to 3 cases in the ephedrine group (\u003cem\u003eP\u003c/em\u003e = 0.068). Although there were no statistically significant differences in postoperative visual analogue scale (VAS) pain scores and between the groups, 14 patients in the phenylephrine group experienced emergence agitation in the PACU, compared to 4 patients in the ephedrine group, which was statistically significant (\u003cem\u003eP\u003c/em\u003e = 0.011). No other statistically significant differences were observed in terms of cardiovascular and neurological complications between the groups ( Table\u0026nbsp;3).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study found that ephedrine's CO was increased when maintaining intraoperative, whereas phenylephrine exhibited a decrease in CO, which is consistent with the results of some previous studies. A study on prophylactic phenylephrine infusion during spinal anesthesia demonstrated decreased CO and cerebral oxygen saturation at various time points\u003csup\u003e[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/sup\u003e\u003csub\u003e,\u003c/sub\u003e Another study comparing ephedrine and phenylephrine revealed that phenylephrine decreased CO, whereas ephedrine maintained it\u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. In turn, a significant correlation was observed between rSO\u003csub\u003e2\u003c/sub\u003e and CO. Reduced CO may trigger compensatory increases in cerebral oxygen uptake, leading to a decrease in mean frontal lobe rSO\u003csub\u003e2\u003c/sub\u003e \u003csup\u003e[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/sup\u003e. One possible mechanism is that CO indirectly causes changes in rSO\u003csub\u003e2\u003c/sub\u003e by affecting cerebral perfusion\u003csup\u003e[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]\u003c/sup\u003e, we all know that cerebral oxygenation depends on the delivery of oxygen to the brain and cerebral oxygen consumption (CMRO\u003csub\u003e2\u003c/sub\u003e), which relies on cerebral blood flow (CBF) and arterial oxygen content. Studies have demonstrated that if CMRO\u003csub\u003e2\u003c/sub\u003e and arterial oxygen content remain constant, changes in rSO\u003csub\u003e2\u003c/sub\u003e correlate with changes in CBF \u003csup\u003e[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. In our study, patients received general anesthesia with relatively consistent doses and depth. Hence, CMRO\u003csub\u003e2\u003c/sub\u003e can be approximated as constant, and variations in CO directly impact CBF. Therefore, the observed changes in rSO\u003csub\u003e2\u003c/sub\u003e may be partly attributed to indirect CBF fluctuations due to changes in CO. In addition, we know that the rapid increase in arterial pressure induced by phenylephrine can lead to increased sympathetic nerve activity in the carotid ganglia \u003csup\u003e[17、18]\u003c/sup\u003e, and the small arteries in the brain are mainly innervated by sympathetic nerve fibers\u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/sup\u003e. Therefore, the phenylephrine-induced enhancement of sympathetic nerve activity leads indirectly to cerebral vasoconstriction and may be related to the decrease in rSO\u003csub\u003e2\u003c/sub\u003e in the present study \u003csup\u003e[17、18]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eThe decrease in rSO\u003csub\u003e2\u003c/sub\u003e in our study was significantly correlated with the incidence of POD, which is consistent with previous studies that patients undergoing cardiac \u003csup\u003e[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e and orthopedic \u003csup\u003e[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]\u003c/sup\u003e surgeries have revealed a dose-response relationship between cerebral oxygen saturation and postoperative neurocognitive disorders. Moreover, a recent large retrospective study indirectly supports this hypothesis, demonstrating that low peripheral oxygen saturation (closely linked to cerebral oxygen saturation) and low carbon dioxide levels (directly reflecting cerebral perfusion) elevate the risk of POD \u003csup\u003e[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/sup\u003e. Wang et al. established a significant correlation between rSO\u003csub\u003e2\u003c/sub\u003e and hypotension, leading to profound delirium \u003csup\u003e[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/sup\u003e. Although our study found a slight decrease in rSO\u003csub\u003e2\u003c/sub\u003e in the ephedrine group as well, We consider that such small fluctuations in rSO\u003csub\u003e2\u003c/sub\u003e are not yet sufficient to alter clinical outcomes. On the other hand, the two drugs do have significant heterogeneity in their effects on cerebral circulation, especially since this study focused on vulnerable populations that may be more susceptible. Similar studies have illustrated that the effects of vasoactive drugs on vulnerable populations may be more pronounced and thus have a profound impact on clinical outcomes. A recent MRI-based study analyzed patients with brain tumors who received ephedrine or phenylephrine to achieve similar MAP endpoints. The results demonstrated that the ephedrine group exhibited higher cerebral blood flow and cerebral tissue oxygenation indices compared to the phenylephrine group. Additionally, the study revealed that phenylephrine disrupted microcirculation, resulting in reduced oxygen extraction, while ephedrine improved both macro- and microcirculation in the brain, enhancing oxygen extraction \u003csup\u003e[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]\u003c/sup\u003e. Previous reports have indicated that phenylephrine treatment in patients with septic shock can reduce HR, impair hepatic and renal perfusion, and compromise kidney function \u003csup\u003e[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn summary, this study reveals the different effects of ephedrine and phenylephrine on the incidence of POD in fragile elderly patients undergoing knee arthroplasty, where ephedrine can be associated with a reduction in the incidence of POD and may be related to perioperative changes in CO and rSO\u003csub\u003e2\u003c/sub\u003e, This study also has some limitations. First, this study was a single-center, small-sample study, multicenter, large-sample studies are still needed to further clarify the different roles of the drugs. Second, some patients in the phenylephrine group of this study used a single dose of atropine intraoperatively, and although the timing of the atropine administration and dosage were different from those in previous studies\u003csup\u003e[25、26]\u003c/sup\u003e, The interference of atropine on the results cannot be absolutely ruled out, and thirdly, in this study, intraoperative CO and rSO\u003csub\u003e2\u003c/sub\u003e changes were monitored by using Vigileo monitor and near-infrared spectroscopy, but there is still a possibility that imprecise monitoring and extracranial contamination may have interfered with the values\u003csup\u003e[27、28]\u003c/sup\u003e.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003ePOD Postoperative delirium\u003c/p\u003e\u003cp\u003ePOCD Postoperative cognitive dysfunction\u003c/p\u003e\u003cp\u003eCO Cardiac output\u003c/p\u003e\u003cp\u003erSO\u003csub\u003e2\u003c/sub\u003e Regional cerebral oxygen saturation\u003c/p\u003e\u003cp\u003eVAS Visual analogue scale\u003c/p\u003e\u003cp\u003ePACU Post-anesthesia care unit\u003c/p\u003e\u003cp\u003eCAM Confusion Assessment Method\u003c/p\u003e\u003cp\u003eASA American society of Aneshesiologists\u003c/p\u003e\u003cp\u003eCMRO\u003csub\u003e2\u003c/sub\u003e Cerebral oxygen consumption\u003c/p\u003e\u003cp\u003eCBF Cerebral blood flow\u003c/p\u003e\u003cp\u003eBIS bispectral index\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe deeply thank our colleagues at the Department of Anesthesiology, Yijishan Hospital of Wannan Medical College, for assistance with the samples.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChangjian Zheng: Conceptualization, Data curation, Funding acquisition, Investigation, Methodology, Project administration, Resources, Software, Writing - original draf. Xian Wen Hu, Bin Wang: Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Resources, Supervision, Writing - review \u0026amp; editing.Hui Peng: Formal analysis, Validation.Xian Wen Hu: Methodology, Resources.Yongquan Chen: Methodology, Resources, Validation.\u0026nbsp;Jiuzhou Fu: \u0026nbsp;Investigation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMajor Research Project of Anhui Provincial Department of Education\u0026nbsp;(KJ2021ZD0030), Key Technologies Research and Development Program of Anhui Province (2022e07020045), Key Projects of Clinical Cultivation Program of the Second Affiliated Hospital of Anhui Medical University (2021LCZD02)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDeclaration section\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs this paper is only part of a series of trials, we have further related trials to conduct, and the data sets generated and/or analyzed during the current study are not publicly available but are available from the corresponding authors at their reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eInouye SK, Westendorp RGJ, Saczynski JS. Delirium in elderly people. Lancet 2014; 383: 911\u0026ndash;22\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu WF, Lin JT, Qiu YK, Dong W, Wan J, Li S, Zheng H, Wu YQ. The role of epigenetic modification in postoperative cognitive dysfunction. Ageing Res Rev. 2023;89:101983.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao B, Ni Y, Tian X. Low plasma cholinesterase activity is associated with postoperative delirium after noncardiac surgery in elderly patients: a prospective observational study. Psychosomatics 2019;60(2):190\u0026ndash;6\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang Y, Zhao X, Dong T, Yang Z, Zhang Q, Zhang Y. Risk factors for postoperative delirium following hip fracture repair in elderly patients: a systematic review and meta-analysis. Aging Clin Exp Res. 2017;29(2):115\u0026ndash;126.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWitlox J, Eurelings LS, de Jonghe JF, Kalisvaart KJ, Eikelenboom P, van Gool WA. Delirium in elderly patients and the risk of postdischarge mortality, institutionalization, and dementia: a meta-analysis. JAMA. 2010;304(4):443\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJin Z, Hu J, Ma D. Postoperative delirium: perioperative assessment, risk reduction, and management. Br J Anaesth. 2020;125(4):492\u0026ndash;504.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu Y, Di M, Li C, Chen M, Yuan K, Shangguan W. Comparing the response of pulse oximetry and regional cerebral oxygen saturation to hypoxia in preschool children. Exp Ther Med. 2020;19(1):353\u0026ndash;358.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhrens E, Tartler TM, Suleiman A, Wachtendorf LJ, Ma H, Chen G, Kendale SM, Kienbaum P, Subramaniam B, Wagner S, Schaefer MS. Dose-dependent relationship between intra-procedural hypoxaemia or hypocapnia and postoperative delirium in older patients. Br J Anaesth. 2023;130(2):e298-e306.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng L, Cannesson M, Alexander BS, Yu Z, Kain ZN, Cerussi AE, Tromberg BJ, Mantulin WW. Effect of phenylephrine and ephedrine bolus treatment on cerebral oxygenation in anaesthetized patients. Br J Anaesth. 2011;107(2):209\u0026ndash;17.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFoss VT, Christensen R, Rokamp KZ, Nissen P, Secher NH, Nielsen HB. Effect of phenylephrine vs. ephedrine on frontal lobe oxygenation during caesarean section with spinal anesthesia: an open label randomized controlled trial. Front Physiol. 2014;5:81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLarson S, Anderson L, Thomson S. Effect of phenylephrine on cerebral oxygen saturation and cardiac output in adults when used to treat intraoperative hypotension: a systematic review. JBI Evid Synth. 2021;19(1):34\u0026ndash;58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKoch KU, Mikkelsen IK, Espelund US, Angleys H, Tietze A, Oettingen GV, Juul N, \u0026Oslash;stergaard L, Rasmussen M. Cerebral Macro- and Microcirculation during Ephedrine versus Phenylephrine Treatment in Anesthetized Brain Tumor Patients: A Randomized Clinical Trial Using Magnetic Resonance Imaging. Anesthesiology. 2021;135(5):788\u0026ndash;803.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrbach-Zinger S, Bizman I, Firman S, Lev S, Gat R, Ashwal E, Vaturi M, Razinski E, Davis A, Shmueli A, Eidelman LA. Perioperative noninvasive cardiac output monitoring in parturients undergoing cesarean delivery with spinal anesthesia and prophylactic phenylephrine drip: a prospective observational cohort study. J Matern Fetal Neonatal Med. 2019;32(19):3153\u0026ndash;3159.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng L, Hou W, Chui J, Han R, Gelb AW. Cardiac Output and Cerebral Blood Flow: The Integrated Regulation of Brain Perfusion in Adult Humans. Anesthesiology. 2015;123(5):1198\u0026ndash;208.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWong FY, Nakamura M, Alexiou T, Brodecky V, Walker AM. Tissue oxygenation index measured using spatially resolved spectroscopy correlates with changes in cerebral blood flow in newborn lambs. Intensive Care Med. 2009;35(8):1464\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWong FY, Nakamura M, Alexiou T, Brodecky V, Walker AM. Tissue oxygenation index measured using spatially resolved spectroscopy correlates with changes in cerebral blood flow in newborn lambs. Intensive Care Med. 2009;35(8):1464\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCassaglia PA, Griffifiths RI, Walker AM. Sympathetic nerve activity in the superior cervical ganglia increases in response to imposed increases in arterial pressure. Am J Physiol Regul Integr Comp Physiol 2008; 294: R1255\u0026ndash;61\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCassaglia PA, Griffifiths RI, Walker AM. Cerebral sympathetic nerve activity has a major regulatory role in the cerebral circulation in REM sleep. J Appl Physiol 2009; 106: 1050\u0026ndash;6\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHamel E. Perivascular nerves and the regulation of cerebrovascular tone. J Appl Physiol 2006; 100: 1059\u0026ndash;64\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSlater JP, Guarino T, Stack J, Vinod K, Bustami RT, Brown JM 3rd, Rodriguez AL, Magovern CJ, Zaubler T, Freundlich K, Parr GV. Cerebral oxygen desaturation predicts cognitive decline and longer hospital stay after cardiac surgery. Ann Thorac Surg. 2009;87(1):36\u0026ndash;44; discussion 44\u0026thinsp;\u0026ndash;\u0026thinsp;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim J, Shim JK, Song JW, Kim EK, Kwak YL. Postoperative Cognitive Dysfunction and the Change of Regional Cerebral Oxygen Saturation in Elderly Patients Undergoing Spinal Surgery. Anesth Analg. 2016;123(2):436\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang X, Feng K, Liu H, Liu Y, Ye M, Zhao G, Wang T. Regional cerebral oxygen saturation and postoperative delirium in endovascular surgery: a prospective cohort study. Trials. 2019;20(1):504.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMorelli A, Lange M, Ertmer C, D\u0026uuml;nser M, Rehberg S, Bachetoni A, D'Alessandro M, Van Aken H, Guarracino F, Pietropaoli P, Traber DL, Westphal M. Short-term effects of phenylephrine on systemic and regional hemodynamics in patients with septic shock: a crossover pilot study. Shock. 2008;29(4):446\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eReinelt H, Radermacher P, Kiefer P, Fischer G, Wachter U, Vogt J, Georgieff M. Impact of exogenous beta-adrenergic receptor stimulation on hepatosplanchnic oxygen kinetics and metabolic activity in septic shock. Crit Care Med. 1999;27(2):325\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFerr\u0026eacute; F, Piel-Julian ML, Tincres F, Ba C, Menut R, Ferrier A, Bosch L, Martin C, Labaste F, Montastruc F, Sommet A, Balardy L, Minville V. A High Postoperative Atropinic Burden is Associated with Postoperative Delirium in Elderly Patients with Hip Fracture: Results of the Prospective, Observational, ATROPAGE Trial. Clin Interv Aging. 2022;17:1931\u0026ndash;1938.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlamer TT, Wauters M, Azermai M, Dur\u0026aacute;n C, Christiaens T, Elseviers M, Vander Stichele R. A Novel Scale Linking Potency and Dosage to Estimate Anticholinergic Exposure in Older Adults: the Muscarinic Acetylcholinergic Receptor ANTagonist Exposure Scale. Basic Clin Pharmacol Toxicol. 2017;120(6):582\u0026ndash;590.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArgueta E, Berdine G, Pena C, Nugent KM. FloTrac\u0026reg; monitoring system: what are its uses in critically ill medical patients? Am J Med Sci. 2015;349(4):352\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKubo Y, Kubo T, Toki T, Yokota I, Morimoto Y. Effects of ephedrine and phenylephrine on cerebral oxygenation: observational prospective study using near-infrared time-resolved spectroscopy. J Clin Monit Comput. 2023;37(5):1171\u0026ndash;1177.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDas S, Mukhopadhyay S, Mandal M, Mandal S, Basu SR. A comparative study of infusions of phenylephrine, ephedrine and phenylephrine plus ephedrine on maternal haemodynamics in elective caesarean section. Indian J Anaesth. 2011;55(6):578\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNgan Kee WD, Lee A, Khaw KS, Ng FF, Karmakar MK, Gin T. A randomized double-blinded comparison of phenylephrine and ephedrine infusion combinations to maintain blood pressure during spinal anesthesia for cesarean delivery: the effects on fetal acid-base status and hemodynamic control. Anesth Analg. 2008;107(4):1295\u0026ndash;302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu X, Hu X, Wu Y, Li Y, Zhang Y, Zhang M, Yang Q. Effects of different BP management strategies on postoperative delirium in elderly patients undergoing hip replacement: A single center randomized controlled trial. J Clin Anesth. 2020;62:109730.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1 Demographic and Clinical Characteristics at Baseline\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" style=\"margin-right: calc(23%); width: 77%;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.36510500807754%\" valign=\"top\"\u003e\n \u003cp\u003eDemographics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.486268174474958%\" valign=\"top\"\u003e\n \u003cp\u003ePhenylephrine\u003c/p\u003e\n \u003cp\u003e(n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.932148626817447%\" valign=\"top\"\u003e\n \u003cp\u003eEphedrine\u003c/p\u003e\n \u003cp\u003e(n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.216478190630049%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"46.36510500807754%\" valign=\"top\"\u003e\n \u003cp\u003eSex, n(%)\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eAge, yr\u003c/p\u003e\n \u003cp\u003eBMI, kg.m\u003csup\u003e-2\u003c/sup\u003e\u003c/p\u003e\n \u003cp\u003eASA, n(%)\u003c/p\u003e\n \u003cp\u003eⅠ\u003c/p\u003e\n \u003cp\u003eⅡ\u003c/p\u003e\n \u003cp\u003eⅢ\u003c/p\u003e\n \u003cp\u003eSmoking, n(%)\u003c/p\u003e\n \u003cp\u003eAlcohol abuse, n(%)\u003c/p\u003e\n \u003cp\u003eSurgical history, n(%)\u003c/p\u003e\n \u003cp\u003eComorbid disease by System\u003c/p\u003e\n \u003cp\u003eCardiovascular, n(%)\u003c/p\u003e\n \u003cp\u003eGastrointestinal, n(%)\u003c/p\u003e\n \u003cp\u003eUrinary tract, n(%)\u003c/p\u003e\n \u003cp\u003eCentral nervous system, n(%)\u003c/p\u003e\n \u003cp\u003eRespiratory, n(%)\u003c/p\u003e\n \u003cp\u003ePreoperative Hb, median (IQR)g/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.486268174474958%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (25)\u003c/p\u003e\n \u003cp\u003e69\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e23\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e2（3）\u003c/p\u003e\n \u003cp\u003e47（78）\u003c/p\u003e\n \u003cp\u003e11（18）\u003c/p\u003e\n \u003cp\u003e18(30)\u003c/p\u003e\n \u003cp\u003e12(20)\u003c/p\u003e\n \u003cp\u003e7(12)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e36(60)\u003c/p\u003e\n \u003cp\u003e15(25)\u003c/p\u003e\n \u003cp\u003e13(22)\u003c/p\u003e\n \u003cp\u003e8(13)\u003c/p\u003e\n \u003cp\u003e6(10)\u003c/p\u003e\n \u003cp\u003e119(78-149)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.932148626817447%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14 (23)\u003c/p\u003e\n \u003cp\u003e68\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e22\u0026plusmn;3\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3（5）\u003c/p\u003e\n \u003cp\u003e44（73）\u003c/p\u003e\n \u003cp\u003e13（22）\u003c/p\u003e\n \u003cp\u003e15(25)\u003c/p\u003e\n \u003cp\u003e14(23)\u003c/p\u003e\n \u003cp\u003e6(10)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e31(52)\u003c/p\u003e\n \u003cp\u003e20(33)\u003c/p\u003e\n \u003cp\u003e10(17)\u003c/p\u003e\n \u003cp\u003e9(15)\u003c/p\u003e\n \u003cp\u003e9(15)\u003c/p\u003e\n \u003cp\u003e123(83-146)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.216478190630049%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.813\u003c/p\u003e\n \u003cp\u003e0.248\u003c/p\u003e\n \u003cp\u003e0.128\u003c/p\u003e\n \u003cp\u003e0.792\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.540\u003c/p\u003e\n \u003cp\u003e0.658\u003c/p\u003e\n \u003cp\u003e0.769\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.358\u003c/p\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003cp\u003e0.487\u003c/p\u003e\n \u003cp\u003e0.793\u003c/p\u003e\n \u003cp\u003e0.408\u003c/p\u003e\n \u003cp\u003e0.629\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eASA:American Society of Anesthesiologists; BMI:body mass index; Hb:hemoglobin\u003c/p\u003e\n\u003cp\u003eThe data are presented as means\u0026plusmn;standard deviation for continous variables and frequency(%) for categorical variables, Data that are not normally distributed are represented by the median (interquartile)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2 \u0026nbsp;Intraoperative Characteristics of Patients Undergoing Surgery\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" style=\"margin-right: calc(12%); width: 88%;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.972536348949916%\" valign=\"top\" style=\"width: 44.5179%;\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.486268174474958%\" valign=\"top\" style=\"width: 19.8287%;\"\u003e\n \u003cp\u003ePhenylephrine\u003c/p\u003e\n \u003cp\u003e(n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.909531502423263%\" valign=\"top\"\u003e\n \u003cp\u003eEphedrine\u003c/p\u003e\n \u003cp\u003e(n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.631663974151857%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"42.972536348949916%\" valign=\"top\" style=\"width: 44.5179%;\"\u003e\n \u003cp\u003eDuration of Surgery, min\u003c/p\u003e\n \u003cp\u003ePACU residence time, min\u003c/p\u003e\n \u003cp\u003eAnaesthetic，median(IQR)\u003c/p\u003e\n \u003cp\u003ePropofol, mg\u003c/p\u003e\n \u003cp\u003eRemifentanil, ug\u003c/p\u003e\n \u003cp\u003eSufentanil, ug\u003c/p\u003e\n \u003cp\u003eRocuronium, mg\u003c/p\u003e\n \u003cp\u003eMonitoring Baseline\u003c/p\u003e\n \u003cp\u003eMAP , mmHg\u003c/p\u003e\n \u003cp\u003eHR, median(IQR), beats/min\u003c/p\u003e\n \u003cp\u003erSO\u003csub\u003e2,\u0026nbsp;\u003c/sub\u003e%\u003c/p\u003e\n \u003cp\u003eCO, median(IQR), L/min\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHemodynamic changes\u003c/p\u003e\n \u003cp\u003eChange in MAP, mmHg\u003c/p\u003e\n \u003cp\u003eChange in HR,beats/min\u003c/p\u003e\n \u003cp\u003eChange in rSO\u003csub\u003e2,\u003c/sub\u003e%\u003c/p\u003e\n \u003cp\u003eChange in CO, L/min\u003c/p\u003e\n \u003cp\u003eBlood loss, median(IQR), ml\u003c/p\u003e\n \u003cp\u003eUrine volum, median(IQR), ml\u003c/p\u003e\n \u003cp\u003eLength of hospital stay, median(IQR), days\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.486268174474958%\" valign=\"top\" style=\"width: 19.8287%;\"\u003e\n \u003cp\u003e97\u0026plusmn;14\u003c/p\u003e\n \u003cp\u003e32\u0026plusmn;8\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e750(680-828)\u003c/p\u003e\n \u003cp\u003e1515\u0026plusmn;384\u003c/p\u003e\n \u003cp\u003e35(31-45)\u003c/p\u003e\n \u003cp\u003e46(43-49)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e93\u0026plusmn;9\u003c/p\u003e\n \u003cp\u003e80(75-86)\u003c/p\u003e\n \u003cp\u003e68\u0026plusmn;4\u003c/p\u003e\n \u003cp\u003e4.6(3.9-5.2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-8.6\u0026plusmn;0.9\u003c/p\u003e\n \u003cp\u003e-12\u0026plusmn;1\u003c/p\u003e\n \u003cp\u003e\u0026minus;8.4\u0026plusmn;0.6\u003c/p\u003e\n \u003cp\u003e-0.4\u0026plusmn;0.06\u003c/p\u003e\n \u003cp\u003e180(150-219)\u003c/p\u003e\n \u003cp\u003e172(156-194)\u003c/p\u003e\n \u003cp\u003e9(7-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"23.909531502423263%\" valign=\"top\"\u003e\n \u003cp\u003e102\u0026plusmn;16\u003c/p\u003e\n \u003cp\u003e31\u0026plusmn;9\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e783(682-868)\u003c/p\u003e\n \u003cp\u003e1537(1285-1800)\u003c/p\u003e\n \u003cp\u003e35(30-40)\u003c/p\u003e\n \u003cp\u003e46(43-51)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e95\u0026plusmn;9\u003c/p\u003e\n \u003cp\u003e79(70-85)\u003c/p\u003e\n \u003cp\u003e67\u0026plusmn;5\u003c/p\u003e\n \u003cp\u003e4.3(3.7-5.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e-9.4\u0026plusmn;0.9\u003c/p\u003e\n \u003cp\u003e10\u0026plusmn;1\u003c/p\u003e\n \u003cp\u003e-1.3\u0026plusmn;0.6\u003c/p\u003e\n \u003cp\u003e0.45\u0026plusmn;0.06\u003c/p\u003e\n \u003cp\u003e190(170-250)\u003c/p\u003e\n \u003cp\u003e170(145-218)\u003c/p\u003e\n \u003cp\u003e8(7-10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.631663974151857%\" valign=\"top\"\u003e\n \u003cp\u003e0.096\u003c/p\u003e\n \u003cp\u003e0.724\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.227\u003c/p\u003e\n \u003cp\u003e0.659\u003c/p\u003e\n \u003cp\u003e0.206\u003c/p\u003e\n \u003cp\u003e0.477\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.225\u003c/p\u003e\n \u003cp\u003e0.351\u003c/p\u003e\n \u003cp\u003e0.198\u003c/p\u003e\n \u003cp\u003e0.122\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.517\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.089\u003c/p\u003e\n \u003cp\u003e0.966\u003c/p\u003e\n \u003cp\u003e0.286\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePACU:Post anesthesia care unit; MAP:Mean arterial pressure; HR:Heart rate; rSO\u003csub\u003e2\u003c/sub\u003e:Regional cerebral oxygen; CO:Cardiac output\u003c/p\u003e\n\u003cp\u003eThe data are presented as means\u0026plusmn;standard deviation for continous variables, Non-normal distribution using median (interquartile)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 3 Side Effects Between the two Groups\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.58064516129032%\" valign=\"top\"\u003e\n \u003cp\u003eSide effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.451612903225808%\" valign=\"top\" style=\"width: 2.5852%;\"\u003e\n \u003cp\u003ePhenylephrine\u003c/p\u003e\n \u003cp\u003e(n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.419354838709676%\" valign=\"top\"\u003e\n \u003cp\u003eEphedrine\u003c/p\u003e\n \u003cp\u003e(n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.548387096774194%\" valign=\"top\" style=\"width: 32.3643%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"47.58064516129032%\" valign=\"top\"\u003e\n \u003cp\u003eNausea/vomiting,n(%)\u003c/p\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003cp\u003ePostoperative day 2\u003c/p\u003e\n \u003cp\u003eVAS Score\u003c/p\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003cp\u003ePostoperative day 2\u003c/p\u003e\n \u003cp\u003eBlood pressure,median(IQR),mmHg\u003c/p\u003e\n \u003cp\u003ePostoperative day 1\u003c/p\u003e\n \u003cp\u003ePostoperative day 2\u003c/p\u003e\n \u003cp\u003eNeurological System\u003c/p\u003e\n \u003cp\u003eEmergence agitation\u003c/p\u003e\n \u003cp\u003eHeadache and dizziness\u003c/p\u003e\n \u003cp\u003eStroke\u003c/p\u003e\n \u003cp\u003eCardiovascular System (PACU)\u003c/p\u003e\n \u003cp\u003eHypotension\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eHypertension\u0026nbsp;\u003c/p\u003e\n \u003cp\u003eBradycardia\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"21.451612903225808%\" valign=\"top\" style=\"width: 2.5852%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e9(15)\u003c/p\u003e\n \u003cp\u003e2(3)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4.0(2.3-4.0)\u003c/p\u003e\n \u003cp\u003e2.0(1.3-3.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e93\u0026plusmn;9\u003c/p\u003e\n \u003cp\u003e91\u0026plusmn;10\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e14（23）\u003c/p\u003e\n \u003cp\u003e1（2）\u003c/p\u003e\n \u003cp\u003e1（2）\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4（7）\u003c/p\u003e\n \u003cp\u003e3（5）\u003c/p\u003e\n \u003cp\u003e2（3）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"17.419354838709676%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3(5)\u003c/p\u003e\n \u003cp\u003e1(2)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e3.0(2.0-4.0)\u003c/p\u003e\n \u003cp\u003e2.0(1.0-3.0)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e93\u0026plusmn;10\u003c/p\u003e\n \u003cp\u003e90\u0026plusmn;11\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4*（7）\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e4（7）\u003c/p\u003e\n \u003cp\u003e1（2）\u003c/p\u003e\n \u003cp\u003e1（2）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.548387096774194%\" valign=\"top\" style=\"width: 32.3643%;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.068\u003c/p\u003e\n \u003cp\u003e0.559\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.120\u003c/p\u003e\n \u003cp\u003e0.531\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.809\u003c/p\u003e\n \u003cp\u003e0.575\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003cp\u003e0.309\u003c/p\u003e\n \u003cp\u003e0.559\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eVAS:Visual Analogue Scale, PACU:Post anesthesia care unit.\u003c/p\u003e\n\u003cp\u003eThe data are presented as means\u0026plusmn;standard deviation for continous variables and frequency(%) for categorical variables, Data that are not normally distributed are represented by the median (interquartile)\u003c/p\u003e\n\u003cp\u003eTable 4 Incidence of POD\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" style=\"margin-right: calc(11%); width: 89%;\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.14711359404097%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.374301675977655%\" valign=\"top\" style=\"width: 22.9218%;\"\u003e\n \u003cp\u003ePhenylephrine\u003c/p\u003e\n \u003cp\u003e(n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.99441340782123%\" valign=\"top\" style=\"width: 22.1625%;\"\u003e\n \u003cp\u003eEphedrine\u003c/p\u003e\n \u003cp\u003e(n=60)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.484171322160147%\" valign=\"top\" style=\"width: 24.6883%;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"33.14711359404097%\" valign=\"top\"\u003e\n \u003cp\u003ePostoperative day1\u003c/p\u003e\n \u003cp\u003ePostoperative day2\u003c/p\u003e\n \u003cp\u003ePostoperative day3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.374301675977655%\" valign=\"top\" style=\"width: 22.9218%;\"\u003e\n \u003cp\u003e20(33)\u003c/p\u003e\n \u003cp\u003e4(7)\u003c/p\u003e\n \u003cp\u003e1(2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.99441340782123%\" valign=\"top\" style=\"width: 22.1625%;\"\u003e\n \u003cp\u003e4(7)\u003c/p\u003e\n \u003cp\u003e2(3)\u003c/p\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.484171322160147%\" valign=\"top\" style=\"width: 24.6883%;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003cp\u003e0.402\u003c/p\u003e\n \u003cp\u003e0.315\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003ePOD:Postoperative delirium\u003c/p\u003e\n\u003cp\u003eNoncontinuous variables are presented as number of subjects (percentage).\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4499979/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4499979/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eDespite equalizing blood pressure(BP), ephedrine and phenylephrine exhibit distinct impacts on rSO2. However, whether this heterogeneity in rSO2 affects the occurrence of POD remains understudied. This study aimed to explore the effects of maintaining BP with ephedrine versus phenylephrine on the incidence of POD in elderly patients undergoing knee arthroplasty under general anesthesia. A total of 120 patients aged 60-90 years undergoing knee arthroplasty were included in this study.The patients were randomly divided into two groups: the ephedrine group and the phenylephrine group. After anesthesia induction, continuous infusion of the respective medication was initiated to maintain intraoperative mean arterial pressure within the normal range (baseline mean arterial pressure ± 20%).The primary outcome measures included the incidence of POD within 1-3 days after the surgery. The incidence of POD on the first day after surgery was lower in the ephedrine group compared to the phenylephrine group (33% vs 7%, P \u0026lt; 0.001 ). However, there was no significant difference in the incidence of POD between the two groups on the second and third postoperative days. During surgery, the ephedrine group exhibited significantly increased CO and rSO2 compared to the phenylephrine group (P \u0026lt; 0.05).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eClinical Trials Registry: ChiCTR2200064849, principal investigator: Changjian Zheng.\u003c/p\u003e","manuscriptTitle":"Effect of Phenylephrine versus Ephedrine on Postoperative Delirium in Elderly Patients Undergoing Knee Arthroplasty General Anaesthesia：A Single-Center Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-13 21:09:48","doi":"10.21203/rs.3.rs-4499979/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-01T04:32:24+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-28T08:55:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-20T12:22:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"225844213324823446984775086282171381178","date":"2024-06-10T07:22:30+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"190749115737346983092110564118884778256","date":"2024-06-07T17:11:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-06-07T15:20:17+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-06-07T15:01:28+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-06-04T12:54:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-05-31T10:16:22+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-05-30T03:02:55+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"0f67cc7d-44bb-4575-acc5-ad869f1a4809","owner":[],"postedDate":"June 13th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":33167950,"name":"Health sciences/Medical research"},{"id":33167951,"name":"Health sciences/Signs and symptoms"}],"tags":[],"updatedAt":"2024-08-01T17:05:38+00:00","versionOfRecord":{"articleIdentity":"rs-4499979","link":"https://doi.org/10.1038/s41598-024-68273-2","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2024-07-27 16:16:06","publishedOnDateReadable":"July 27th, 2024"},"versionCreatedAt":"2024-06-13 21:09:48","video":"","vorDoi":"10.1038/s41598-024-68273-2","vorDoiUrl":"https://doi.org/10.1038/s41598-024-68273-2","workflowStages":[]},"version":"v1","identity":"rs-4499979","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4499979","identity":"rs-4499979","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}