Auriculotherapy for controlled hypotension during functional endoscopic surgery of the paranasal sinuses under general anesthesia: AuriFESS, a feasibility randomized pilot study

Auriculotherapy for controlled hypotension during functional endoscopic surgery of the paranasal sinuses under general anesthesia: AuriFESS, a feasibility randomized pilot study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Auriculotherapy for controlled hypotension during functional endoscopic surgery of the paranasal sinuses under general anesthesia: AuriFESS, a feasibility randomized pilot study Fabio Sbaraglia, Carmela Riso, Giorgia Spinazzola, Demetrio Del Prete, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9105769/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 13 You are reading this latest preprint version Abstract Background Administration of hypotensive drugs is common to induce controlled hypotension during surgery but dose-dependent side effects could limit their use. The primary hypothesis of our study is that the application of magnetic ball-plasters for auriculotherapy could be effective in achieving a hypotensive effect during general anesthesia. Methods Single-center, randomized controlled trial conducted in Italy between June and July 2024 and involving adult patients undergoing functional endoscopic sinus surgery (FESS). Magnetic ball plasters for auriculotherapy were applied to the treatment group (ATG), while a sham auriculotherapy was simulated for the control group (CG). Both groups received intravenous anesthesia with propofol and remifentanil and a continuous infusion of nitroglycerin was ensured to maintain a mean arterial pressure (MAP) between 60 and 70 mmHg. The primary outcome was the median intraoperative infusion rate of nitroglycerin, calculated as the total amount administered divided by patient body weight and duration of surgery. Secondary outcomes were: difference in MAP values between the two groups measured at predefined time points during the perioperative period and on first postoperative day; surgeon’s qualitative assessment of the surgical field in terms of bleeding. Results Among 50 patients enrolled, 40 were randomized and final analysis was completed on a sample of 33 patients. The ATG required lower doses of nitroglycerin compared with the CG to maintain MAP within target range, with a median infusion rate of 0.03 [IQR 0.01-0.07] μg/kg/min vs. 0.09 [IQR 0.04-0.16] μg/kg/min, respectively (P=0.041). Compared to baseline values, MAP significantly decreased in both groups during surgery (P <0.001), and controlled hypotension was maintained for the entire procedural time. At discharge from the recovery room and on first postoperative day MAP was comparable to preoperative values in both groups. No significant differences were reported in terms of qualitative assessment of the surgical field between the two cohorts. Conclusions In this randomized controlled trial auriculotherapy was effective in maintaining a hypotensive status during general anesthesia. Trial registration: Clinicaltrial.gov (NCT06182982), Principal investigator: Fabio Sbaraglia, Date of registration: December 13, 2023). Anesthesia Acupuncture Auriculotherapy Nitroglycerin Total Intravenous Anesthesia Controlled Hypotension Figures Figure 1 Figure 2 Figure 3 Background Traditional anesthetic strategies are increasingly being complemented by a multimodal approach that incorporates acupuncture techniques.[ 1 ] The concept of acupuncture–drug balanced anesthesia has recently emerged, integrating acupuncture with conventional anesthetic management to improve patient outcomes.[ 2 , 3 ] Enhanced Recovery After Surgery (ERAS) programs have begun to acknowledge these benefits, with large-scale data showing promising results across multiple outcomes.[ 4 ] Acupuncture may modulate autonomic responses to surgical stress throughout the perioperative period.[ 5 , 6 ] This attenuation of the physiological response to surgical injury has been attributed to several mechanisms, including a reduction in peripheral vascular resistance, modulation of the renin–angiotensin–aldosterone system, central effects on premotor sympathetic pathways, and decreased release of epinephrine and norepinephrine.[ 7 – 9 ] Auriculotherapy (AT), a variant of traditional acupuncture based on stimulation of specific ear points, has been successfully used in patients with essential hypertension. When combined with antihypertensive medications, AT has been shown to reduce blood pressure and improve achievement of target blood pressure levels.[ 10 , 11 ] Many surgical procedures require controlled hypotension to minimize intraoperative bleeding and to optimize visualization of the surgical field.[ 12 ] Currently, pharmacological induction of hypotension remains the standard approach; however, its use may be limited by dose-dependent adverse effects.[ 13 ] To date, no study has evaluated the cardiovascular effects of auriculotherapy during anesthesia. Therefore, the aim of this pilot study is to evaluate whether the application of auriculotherapy magnetic ball plasters can induce controlled hypotension during functional endoscopic sinus surgery (FESS) performed under general anesthesia. Material and Methods This single-center, randomized controlled study was conducted between June and July 2024 at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki. It was approved on December 7, 2023 by the Institutional Ethics Committee (Comitato Etico Territoriale Lazio Area 3 (ID number: 5828).The trial was registered before patient enrolment at Clinicaltrial.gov (NCT06182982), Principal investigator: Fabio Sbaraglia, Date of registration: December 13, 2023). Written informed consent was obtained from all subjects included in the trial. The manuscript adheres to the Consolidated Standards of Reporting Trials (CONSORT) guidelines. Inclusion criteria were adult patients < 70 years old of either gender with American Society of Anesthesiologists (ASA) physical status I-III scheduled for elective FESS surgery under general anesthesia. Exclusion criteria were: pregnancy status; New York Heart Association class > III; ASA class > III; body mass index (BMI) > 35 kg/m 2 ; previous myocardial infarction or neurovascular diseases; secondary or uncontrolled hypertension despite adequate treatment (defined as preoperative mean arterial pressure (MAP) > 125 mmHg); carotid stenosis > 50%; previous treatment with antineoplastic agents; anatomic alterations of the auricles; allergy or intolerance to drugs specified in the clinical protocol; known allergy to nickel or metal present in the magnetic spheres; refusal of informed consent or inability to express it. Randomization process One independent research team member was responsible for the randomization process and randomized assignments were kept in sequentially numbered, opaque, sealed and stapled envelopes. Complete randomization with parallel assignment was performed using the random number generator in SPSS 23.0 (IBM Corp, Armonk, NY). Patients were divided in two arms, a treatment group (ATG) and a control group (CG). Eligibility of the patients was assessed by an investigator involved in the study and the envelopes were opened before the start of the procedure by a research coordinator. Participants, the attending anesthesiologist, the surgeon and data analysts were blinded to group assignment. Intraoperative data were gathered by a researcher not involved in the study. Interventions In the preoperative holding area, the auriculotherapy group (ATG) received treatment based on the Nogier technique,[ 14 ] and current literature,[ 10 , 15 – 18 ] by a trained physician with more than 5 years of experience in acupuncture techniques. The physician who applied the ball plasters was not involved in the anesthesiological management of the patient during surgery. Magnetic silver ball plasters 800 Gauss, (Shenlong Medical Health Product Co.Ltd, Gangzi Cun, Jiangsu, 215213, China) were applied 30 minutes before induction of anesthesia. Treatment was primarily applied to the left auricle at the following points: Laterality Point; Shen-men; Zero Point; Neurovegetative Control Point; Lowering Blood Pressure Point; Cardiac Regulatory Point). On the right auricle, only the Laterality Point was stimulated (Fig. 1 ). The control group (CG) received sham auriculotherapy. In the absence of well-established sham protocols in the literature, random auricular points were gently touched with a pencil, without application of magnetic balls.[ 19 ] In both groups, the auricle was subsequently covered with gauze to maintain blinding of the patient, surgeon, and anesthesiologist involved in the procedure. After 30 minutes all patients were transferred to the operating theatre, where they received a standard anesthesia protocol. Under multiparametric monitoring with non-invasive blood pressure measurement, 3-lead electrocardiogram, pulse oximetry, bispectral index (BIS™ monitoring, Medtronic, CO, US) and neuromuscular transmission monitoring. Ringer Lactate solution was administered at an infusion rate of 8 ml/kg/h before induction of anesthesia, followed by an infusion of 2–4 ml/kg/h intraoperatively. Target controlled infusion anesthesia (Alaris™ PK Syringe Pump, Fresenius Kabi, Germany), was started with propofol at an effect site concentration of 6 µg/ml and remifentanil at 6 ng/ml, while intubation was facilitated by fentanyl 1 µg/kg and rocuronium bromide 0.6 mg/kg. The patient was then connected to mechanical ventilator settled to maintain EtCO 2 between 30 and 35 mmHg. Propofol infusion was decreased to an effect site concentration of 3–4 µg/ml to maintain bispectral index between 40 and 60, while remifentanil was maintained at 4–5 ng/ml. During surgical preparation patients received an initial low dose infusion of nitroglycerin at 0.1 µg/kg/min, titrated on a non-invasive MAP targeted between 60 and 70 mmHg, measured every 5 minutes. Patients were withdrawn from the study in cases in the event of accidental removal of the gauze used to maintain patient blinding. All infusions were discontinued at the end of surgery, and following extubation, patients were transferred to the recovery room, where the auricles were uncovered and any adhesive materials removed. At the end of the procedure, the surgeon was asked to assess the quality of the surgical field in terms of bleeding using a 5-point Likert scale (1 = Very Dissatisfied, 2 = Dissatisfied, 3 = Neutral/Unsure, 4 = Satisfied, 5 = Very Satisfied). Postoperative monitoring was ensured for at least 30 minutes, after which patients were discharged to the ward. On the first postoperative day, MAP was measured to all patients by ward nurses during the morning round. Outcomes The primary outcome was the median intraoperative infusion rate of nitroglycerin, calculated as the total amount administered divided by patient body weight and duration of surgery, and expressed in µg/kg/min. The secondary outcome was the difference in MAP values between the two groups measured at predefined time points during the perioperative period: T0 (upon arrival in the preoperative holding area), T1 (before skin incision at steady-state drug concentration), T2 (30 minutes after anesthesia induction), T3 (at the end of surgery, before discontinuation of anesthesia), T4 (at discharge from the recovery room), and T5 (on the first postoperative day). An additional outcome was the surgeon’s qualitative assessment of the surgical field in terms of bleeding. Exploratory outcomes included differences in perioperative heart rate (HR), duration of surgery and anesthesia, cumulative doses of administered anesthetic drugs, and the occurrence of any complication before hospital discharge, assessed by reviewing in-hospital electronic medical records. Sample size calculation /Statistical analysis Given the exploratory nature of the study and the limited literature available on the topic, the study was designed as a pilot study and a formal sample size calculation was not performed. According to the rules of thumb proposed by Birkett and Day for pilot studies,[ 20 ] we therefore plan to enroll 20 patients per group, which is consistent with the number of cases typically observed at our clinical facility. Data are displayed as mean ± standard deviation, median (interquartile range, IQR) for numerical data or number of events (%) for categorical data. The normality distribution of numerical data was assessed with Shapiro-Wilk test and visually by histograms. Categorical variables were evaluated with the Chi-square test or Fisher’s exact test in case of expected frequencies < 5. Continuous variables were compared with unpaired Student T-test with corresponding 95% confidence intervals, or using 2-sample Wilcoxon rank-sum test and Hodges–Lehman estimation of location shift with corresponding asymptotic 95% CI in case of not normally distributed variables. Repeated measures were analyzed using two-way repeated-measures analysis of variance (ANOVA), with post-hoc pairwise comparisons performed using the Bonferroni correction. A P value < 0.05 was considered statistically significant. SPSS version 15 (IBM Corporation, Chicago, IL, USA) for Windows (Microsoft Corporation, Redmond, WA, USA) and R (R Foundation for Statistical Computing) were used for data analysis. Results Between January and June 2024, 50 patients were screened for eligibility, 40 met the inclusion criteria and were randomized. Twenty patients were allocated to the auriculotherapy group (ATG) and 20 to the control group (CG). Final analysis was performed on 16 patients in the ATG and 17 in the CG (Fig. 2 ). No significant differences were observed between the two cohorts with respect to demographic and clinical characteristics (Table 1 ). Anesthesia duration was comparable between the two groups (86 [IQR 77–122] minutes in the ATG vs. 75 [IQR 60–135] minutes in the CG, P = 0.678. No adverse events related to the acupuncture technique were recorded. Table 1 Demographic, medical and surgical characteristics of the study population (n = 33) Characteristic Auriculotherapy group (n = 16) Control group (n = 17) Age, years 46 (13) 47 (19) Female 7 (44) 9 (53) Male 9 (56) 8 (44) Height, cm 174 (9) 171 (11) Weight, kg 71 (10) 65 (13) Body mass index, kg/m 2 23 (3) 22 (3) ASA status 1 2 (12) 7 (41) 2 11 (69) 9 (53) 3 3 (19) 1 (6) Medical history Hypertension 3 (19) 4 (23) Dyslipidemia 1 (6) 1 (6) Smokers 5 (31) 3 (17) Depression/anxiety disorder 1 (6) 2 (12) Diabetes 0 (0) 1 (6) Hypothyroidism 3 (19) 2 (12) β-blockers 1 (6) 2 (12) ACE inhibitors 1 (6) 0 (0) Calcium channel blockers 1 (6) 2 (12) Statins 1 (6) 1 (6) Oral hypoglycemic agents 0 (0) 1 (6) Antidepressants/benzodiazepines 1 (6) 2 (12) Indication for FESS Chronic sinusitis 6 (38) 7 (41) Deviated nasal septum 5 (31) 5 (29.5) Nasal polyposis 5 (31) 5 (29.5) Data are displayed as n (%) or mean (standard deviation). ASA: American Society of Anesthesiologists. ACE: angiotensin converting enzyme. FESS: functional endoscopic sinus surgery. Table 2 Primary, secondary and exploratory outcomes according to study group Characteristic Auriculotherapy Group (n = 16) Control Group (n = 17) 95% CI or median difference‡ (95% CI) P value Primary outcome Nitroglycerin infusion rate, µg/kg/min 0.03 (0.01; 0.07) 0.09 (0.04; 0.16) -0.04 (-0.10 to -0.00) 0.043 Secondary outcomes Mean blood pressure, mmHg -T0: Upon arrival in the preoperative holding area 103 (92; 114) 98 (89; 104) 5 (-5 to 17) 0.279 -T1: Before skin incision 64 (8) 72 (17) -17 to 2 0.130 -T2: 30 minutes after anesthesia induction 68 (11) 65 (11) -5 to 11 0.446 -T3: At end of surgery before discontinuation of anesthetic drugs 70 (10) 67 (9) -3 to 11 0.297 -T4: At discharge from the recovery room 103 (11) 99 (12) -4 to 13 0.307 -T5: On the first postoperative day 100 (95; 110) 103 (98; 107) 0 (-6 to 6) > 0.999 Surgeon’s assessment of the surgical field in terms of bleeding Very dissatisfied 1 (6) 0 (0) 0.484 Dissatisfied 0 (0) 0 (0) > 0.999 Neutral 1 (6) 2 (12) > 0.999 Satisfied 4 (25) 3 (18) 0.688 Very satisfied 10 (63) 12 (70) 0.622 Other exploratory outcomes Heart Rate, bpm -T0: Upon arrival in the preoperative holding area 74 (67; 81) 79 (69; 99) -5 (-17 to 7) 0.551 -T1: Before skin incision 77 (17) 75 (11) -8 to 12 0.670 -T2: 30 minutes after anesthesia induction 75 (16) 74 (12) -9 to 11 0.878 -T3: At end of surgery before discontinuation of anesthetic drugs 76 (17) 73 (10) -6 to 13 0.471 Surgery duration, min 78 (55; 93) 52 (43; 117) 9 (-28 to 42) 0.614 Anesthesia duration, min 86 (77; 122) 75 (60; 135) 10 (-33 to 35) 0.678 Propofol, mg 1021 (473) 830 (406) -123 to 506 0.223 Remifentanil, mcg/kg/min 0.11 (0.08; 0.17) 0.14 (0.11; 0.22) -0.02 (-0.07 to 0.02) 0.366 Comparison of randomized groups on primary and secondary outcomes. Data are presented as n (%), or median (interquartile range). Group difference is reported with corresponding 95% CI for normally distributed variables, or as median difference with 95% CI estimated using Hodges-Lehmann estimator. CI: Confidence Interval. P value corresponded to t -test, Wilcoxon rank sum test, Chi-square or Fisher’s exact test. Drugs administration The ATG required significantly lower doses of nitroglycerin to maintain MAP within the target range compared with the CG, with a median infusion rate of 0.03 [IQR 0.01–0.07] µg/kg/min vs. 0.09 [IQR 0.04–0.16] µg/kg/min, respectively (P = 0.041). No statistically significant differences were observed between groups in the cumulative administered doses of anesthetic agents. Hemodynamics Hemodynamic variables were analyzed and compared between groups using repeated-measures analysis of variance. Compared to baseline values, MAP significantly decreased in both groups during surgery (P < 0.001), and controlled hypotension was maintained for the entire procedural time. At discharge from the recovery room and on first postoperative day MAP was comparable to preoperative values in both groups (Fig. 3). HR was not significantly different between the two groups at any time point. Surgical field quality assessment No significant differences were reported in terms of qualitative assessment of the surgical field between the two cohorts. Discussion The main finding of the present study is that a specific auricular acupuncture technique may be an effective complementary measure to modulate sympathetic nervous system activity, as reflected by a reduced requirement for nitroglycerin infusion to maintain mean arterial pressure within a safe target range during general anesthesia for functional endoscopic sinus surgery. Acupuncture techniques have been increasingly incorporated into anesthetic practice for various therapeutic purposes. While their use is well established outside the operating room, intraoperative application remains limited, largely due to the scarcity of high-quality supporting evidence.[ 21 ] Existing literature suggests that acupuncture can significantly reduce blood pressure in awake patients receiving antihypertensive therapy, although it is ineffective as a stand-alone treatment.[ 5 ] Several mechanisms of action have been proposed, including analgesic, autonomic, and neuroendocrine effects.[ 22 ] Our findings are consistent with previous reports on acupuncture, suggesting a potential synergistic interaction with nitroglycerin infusion. Although nitroglycerin is only one of several agents available for achieving controlled hypotension, we considered it the most suitable option for evaluating the intraoperative effects of auriculotherapy. Nitroglycerin-induced controlled hypotension has not been associated with reductions in cerebral oxygen saturation or postoperative cognitive dysfunction[ 23 ] and it has been shown to preserve microvascular perfusion.[ 24 – 25 ] Moreover, its short half-life allows rapid titration to the target MAP, thereby minimizing the risk of bias in the analysis of the primary outcome. Notably, the infusion rate of nitroglycerin required to achieve the target hemodynamic profile was significantly reduced in the treatment group, despite comparable anesthetic drug infusion dosages. This finding suggests the feasibility of an “acupuncture-drug balanced anesthesia” approach, where reduced drug consumption aligns with the multimodal strategies promoted by the ERAS protocols.[ 2 , 26 ] Although our experience showed a direct hypotensive action of AT, it is unclear if this effect is synergistic or additive with nitroglycerin. The study design does not allow to clarify the underlying mechanisms of action, nor does it permit extrapolation of a similar interaction with other hypotensive agents. The mechanisms by which acupuncture lowers blood pressure remain incompletely understood. Current evidence suggests that its hypotensive effects may be mediated through multiple pathways, including modulation of the autonomic nervous system, cardiovascular regulatory centers, and the renin–angiotensin–aldosterone system. Auricular acupuncture appears to have a favorable safety profile, with most reported adverse events being mild and transient.[ 27 ] The hypotensive effect of auriculotherapy appeared to be negligible in the postoperative period, as MAP values at discharge from the recovery room and on the first postoperative day were comparable to preoperative levels. One possible explanation is the short duration of action of AT, combined with the lower intraoperative exposure to nitroglycerin in the treatment group. Moreover, auriculotherapy is typically administered as a chronic intervention,[ 28 ] whereas in the present study it was limited to the intraoperative period. The loss of efficacy observed in the early postoperative period supports the hypothesis that AT may play an adjunctive role when used in combination with other therapies; however, this interpretation is speculative and warrants further investigation. Nevertheless, postoperative hemodynamics data was not associated with safety concerns, and standard monitoring protocols appeared sufficient to ensure safe patient recovery and discharge. In our sample, AT did not show any effects on heart rate, which remained comparable between groups throughout the study period. Moreover, the nitroglycerin doses required in both groups did not result in clinically relevant tachycardia, a known common side effect that could limit the use of nitroglycerin. As expected, the quality of the surgical field was similar between groups. Intraoperative bleeding appeared to be primarily related to MAP values, irrespective of the method used to achieve the hypotensive target. This finding is consistent with previous literature demonstrating that controlled hypotension improves surgical conditions during FESS regardless of the agent or technique employed.[ 13 ] Although adverse events related to auricular acupuncture—such as auricular hematoma, local erythema and swelling, headache, and palpitations—have been reported in the literature,[ 10 , 29 ] no technique-related adverse events were observed in our study population, supporting the safety profile of the technique. Limitations This study has several limitations. First of all, the small sample size limits generalizability of the results. Moreover, in the absence of established evidence, the selection of auricular acupoints and the duration of magnetic ball application were based on clinical practice. Future research should compare different acupoint combinations to identify the most effective treatment strategy. In addition, the control group received sham auriculotherapy, which is not yet standardized across acupuncture trials. Although our findings are promising, they require validation in larger and more diverse patient populations and should be replicated using alternative hypotensive agents. Conclusions Auriculotherapy may exert an independent hypotensive effect in patients undergoing functional endoscopic sinus surgery reducing pharmacological requirements for maintenance of controlled hypotension; however, its efficacy appears to be limited to the intraoperative period. Although the underlying mechanism of action remains unclear, its integration into a multimodal perioperative strategy within ERAS protocols may help optimize the balance between therapeutic benefits and risks while promoting faster recovery. Future studies should further investigate the potential role of acupuncture as a stand-alone intervention and explore whether repeated applications could allow for a more sustained blood pressure control. Abbreviations ASA American Society of Anesthesiologists AT auriculotherapy ATG auriculotherapy group BMI body mass index CG control group CONSORT Consolidated Standards of Reporting Trials ERAS Enhanced Recovery After Surgery FESS functional endoscopic sinus surgery MAP mean arterial pressure Declarations Availability of data and materials: The data that support the findings of this study are available on request from the corresponding author. Funding: Support was provided solely from institutional and/or departmental sources. Competing interests: No potential conflict of interest relevant to this article was reported. Ethics approval and consent to participate: It was approved on December 7, 2023 by the Institutional Ethics Committee (Comitato Etico Territoriale Lazio Area 3 (ID number: 5828). This research accomplishes with all the international requirements for ethics in research. Clinical trial registration number: Clinicaltrial.gov (NCT06182982), Principal investigator: Fabio Sbaraglia, Date of registration: December 13, 2023). Author Contributions FS CM DDP conceived this study; CM DDP performed auricolo and sham therapy; CTC DMM operated as blinded anesthesiologist and provided data entry; SS managed data entry; FS GS wrote the first draft of the manuscript; CM AP e GS edited first draft; GS AP performed the statistical analyses. MR RM JG edited and revised final manuscript. All authors revised the manuscript critically. All have given their final approval of the version to be published. References Zhang J, Liu L, Zhu M, et al. 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The effects of auricular acupressure on blood pressure, stress, and sleep in elders with essential hypertension: a randomized single-blind sham-controlled trial. Eur J Cardiovasc Nurs. 2023;22(6):610–619. Bäumler P, Zhang W, Stübinger T, et al. Acupuncture-related adverse events: systematic review and meta-analyses of prospective clinical studies. BMJ Open 2021;11:e045961. 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-9105769","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":616521174,"identity":"25655e71-11e7-46d0-9ef5-90e3660786cd","order_by":0,"name":"Fabio 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Riso","email":"","orcid":"","institution":"Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore","correspondingAuthor":false,"prefix":"","firstName":"Carmela","middleName":"","lastName":"Riso","suffix":""},{"id":616521176,"identity":"d52c56ca-1791-4ac5-aa4e-3b78629b83d4","order_by":2,"name":"Giorgia Spinazzola","email":"","orcid":"","institution":"Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore","correspondingAuthor":false,"prefix":"","firstName":"Giorgia","middleName":"","lastName":"Spinazzola","suffix":""},{"id":616521178,"identity":"762d897a-893e-49fd-8e34-370b8203dd1b","order_by":3,"name":"Demetrio Del Prete","email":"","orcid":"","institution":"Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore","correspondingAuthor":false,"prefix":"","firstName":"Demetrio","middleName":"Del","lastName":"Prete","suffix":""},{"id":616521179,"identity":"518facc0-5d8b-486f-999e-927d6acdddc9","order_by":4,"name":"Cosimo Tommaso Caputo","email":"","orcid":"","institution":"Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore","correspondingAuthor":false,"prefix":"","firstName":"Cosimo","middleName":"Tommaso","lastName":"Caputo","suffix":""},{"id":616521180,"identity":"74566574-32dd-4ff1-8552-7e0c096f6932","order_by":5,"name":"Daniela Maria Micci","email":"","orcid":"","institution":"Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore","correspondingAuthor":false,"prefix":"","firstName":"Daniela","middleName":"Maria","lastName":"Micci","suffix":""},{"id":616521182,"identity":"97981f97-fdb4-49a4-b957-b3a10ebae62f","order_by":6,"name":"Alessandra Piersanti","email":"","orcid":"","institution":"Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore","correspondingAuthor":false,"prefix":"","firstName":"Alessandra","middleName":"","lastName":"Piersanti","suffix":""},{"id":616521183,"identity":"31754d84-c4ef-4dee-aa0a-c8856531432d","order_by":7,"name":"Roberta Monzani","email":"","orcid":"","institution":"Humanitas Research Hospital","correspondingAuthor":false,"prefix":"","firstName":"Roberta","middleName":"","lastName":"Monzani","suffix":""},{"id":616521184,"identity":"2c4afd9f-7da1-4461-8221-6ceae21d3858","order_by":8,"name":"Jacopo Galli","email":"","orcid":"","institution":"Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore","correspondingAuthor":false,"prefix":"","firstName":"Jacopo","middleName":"","lastName":"Galli","suffix":""},{"id":616521185,"identity":"3e1466fe-e8b8-446f-95db-dcb30767b951","order_by":9,"name":"Stefano Settimi","email":"","orcid":"","institution":"Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore","correspondingAuthor":false,"prefix":"","firstName":"Stefano","middleName":"","lastName":"Settimi","suffix":""},{"id":616521186,"identity":"d157feb1-1a63-4993-b52e-b6b424ae8fa0","order_by":10,"name":"Marco Rossi","email":"","orcid":"","institution":"Fondazione Policlinico Agostino Gemelli IRCCS, Università Cattolica del Sacro Cuore","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Rossi","suffix":""}],"badges":[],"createdAt":"2026-03-12 14:10:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9105769/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9105769/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106309626,"identity":"ed9314cc-95ae-4a35-b20f-f893011587d1","added_by":"auto","created_at":"2026-04-07 10:18:45","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":41444,"visible":true,"origin":"","legend":"\u003cp\u003eAuriculotherapy magnetic ball plasters.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eRight Auricle\u003c/strong\u003e: A Laterality Point\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eLeft Auricle:\u003c/strong\u003e A Laterality Point; B Shen-men; C Zero-Point; D Neurovegetative Control Point; E Lowering Blood Pressure Point; F Cardiac Regulatory Point\u003c/p\u003e","description":"","filename":"AuriFESSFigure1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9105769/v1/9a9495dcb751ebcd4aedd7e9.jpeg"},{"id":106309627,"identity":"29b7811a-4066-408c-8a3f-35f6e6522e3b","added_by":"auto","created_at":"2026-04-07 10:18:45","extension":"jpeg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":69281,"visible":true,"origin":"","legend":"\u003cp\u003eCONSORT flow diagram\u003c/p\u003e","description":"","filename":"AurifessFigure2CONSORTFLOWDIAGRAM.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9105769/v1/e7edc97606c1e6c324978ce4.jpeg"},{"id":106309625,"identity":"904889fa-71d9-4bb1-a886-a19afa008f85","added_by":"auto","created_at":"2026-04-07 10:18:45","extension":"jpeg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":41536,"visible":true,"origin":"","legend":"\u003cp\u003eBox plot of mean arterial pressure (MAP) values at predefined study time points in the two groups. Group 1: control group, Group 2: auriculotherapy group. T0: upon arrival in the preoperative holding area; T1: before skin incision at steady-state drug concentration; T2: mid of surgery; T3: at the end of surgery, before discontinuation of anesthesia; T4: at discharge from the recovery room; T5: on the first postoperative day.\u003c/p\u003e","description":"","filename":"AurifessFigure3.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-9105769/v1/7553f89a1324d048cc8f9c98.jpeg"},{"id":106403968,"identity":"f2c46b3e-93fe-40ca-99f2-ff7c1960e97f","added_by":"auto","created_at":"2026-04-08 09:15:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":999594,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9105769/v1/282610f4-a309-4227-adf8-5feedc6ce6b9.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Auriculotherapy for controlled hypotension during functional endoscopic surgery of the paranasal sinuses under general anesthesia: AuriFESS, a feasibility randomized pilot study","fulltext":[{"header":"Background","content":"\u003cp\u003eTraditional anesthetic strategies are increasingly being complemented by a multimodal approach that incorporates acupuncture techniques.[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] The concept of acupuncture\u0026ndash;drug balanced anesthesia has recently emerged, integrating acupuncture with conventional anesthetic management to improve patient outcomes.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] Enhanced Recovery After Surgery (ERAS) programs have begun to acknowledge these benefits, with large-scale data showing promising results across multiple outcomes.[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAcupuncture may modulate autonomic responses to surgical stress throughout the perioperative period.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] This attenuation of the physiological response to surgical injury has been attributed to several mechanisms, including a reduction in peripheral vascular resistance, modulation of the renin\u0026ndash;angiotensin\u0026ndash;aldosterone system, central effects on premotor sympathetic pathways, and decreased release of epinephrine and norepinephrine.[\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAuriculotherapy (AT), a variant of traditional acupuncture based on stimulation of specific ear points, has been successfully used in patients with essential hypertension. When combined with antihypertensive medications, AT has been shown to reduce blood pressure and improve achievement of target blood pressure levels.[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] Many surgical procedures require controlled hypotension to minimize intraoperative bleeding and to optimize visualization of the surgical field.[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] Currently, pharmacological induction of hypotension remains the standard approach; however, its use may be limited by dose-dependent adverse effects.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTo date, no study has evaluated the cardiovascular effects of auriculotherapy during anesthesia.\u003c/p\u003e \u003cp\u003eTherefore, the aim of this pilot study is to evaluate whether the application of auriculotherapy magnetic ball plasters can induce controlled hypotension during functional endoscopic sinus surgery (FESS) performed under general anesthesia.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cp\u003eThis single-center, randomized controlled study was conducted between June and July 2024 at Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy, in accordance with Good Clinical Practice guidelines and the principles of the Declaration of Helsinki.\u003c/p\u003e \u003cp\u003eIt was approved on December 7, 2023 by the Institutional Ethics Committee (Comitato Etico Territoriale Lazio Area 3 (ID number: 5828).The trial was registered before patient enrolment at Clinicaltrial.gov (NCT06182982), Principal investigator: Fabio Sbaraglia, Date of registration: December 13, 2023). Written informed consent was obtained from all subjects included in the trial.\u003c/p\u003e \u003cp\u003eThe manuscript adheres to the Consolidated Standards of Reporting Trials (CONSORT) guidelines.\u003c/p\u003e \u003cp\u003eInclusion criteria were adult patients\u0026thinsp;\u0026lt;\u0026thinsp;70 years old of either gender with American Society of Anesthesiologists (ASA) physical status I-III scheduled for elective FESS surgery under general anesthesia. Exclusion criteria were: pregnancy status; New York Heart Association class\u0026thinsp;\u0026gt;\u0026thinsp;III; ASA class\u0026thinsp;\u0026gt;\u0026thinsp;III; body mass index (BMI)\u0026thinsp;\u0026gt;\u0026thinsp;35 kg/m\u003csup\u003e2\u003c/sup\u003e; previous myocardial infarction or neurovascular diseases; secondary or uncontrolled hypertension despite adequate treatment (defined as preoperative mean arterial pressure (MAP)\u0026thinsp;\u0026gt;\u0026thinsp;125 mmHg); carotid stenosis\u0026thinsp;\u0026gt;\u0026thinsp;50%; previous treatment with antineoplastic agents; anatomic alterations of the auricles; allergy or intolerance to drugs specified in the clinical protocol; known allergy to nickel or metal present in the magnetic spheres; refusal of informed consent or inability to express it.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eRandomization process\u003c/h2\u003e \u003cp\u003eOne independent research team member was responsible for the randomization process and randomized assignments were kept in sequentially numbered, opaque, sealed and stapled envelopes. Complete randomization with parallel assignment was performed using the random number generator in SPSS 23.0 (IBM Corp, Armonk, NY). Patients were divided in two arms, a treatment group (ATG) and a control group (CG).\u003c/p\u003e \u003cp\u003eEligibility of the patients was assessed by an investigator involved in the study and the envelopes were opened before the start of the procedure by a research coordinator. Participants, the attending anesthesiologist, the surgeon and data analysts were blinded to group assignment. Intraoperative data were gathered by a researcher not involved in the study.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInterventions\u003c/h3\u003e\n\u003cp\u003eIn the preoperative holding area, the auriculotherapy group (ATG) received treatment based on the Nogier technique,[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and current literature,[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan additionalcitationids=\"CR16 CR17\" citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] by a trained physician with more than 5 years of experience in acupuncture techniques. The physician who applied the ball plasters was not involved in the anesthesiological management of the patient during surgery.\u003c/p\u003e \u003cp\u003eMagnetic silver ball plasters 800 Gauss, (Shenlong Medical Health Product Co.Ltd, Gangzi Cun, Jiangsu, 215213, China) were applied 30 minutes before induction of anesthesia. Treatment was primarily applied to the left auricle at the following points: Laterality Point; Shen-men; Zero Point; Neurovegetative Control Point; Lowering Blood Pressure Point; Cardiac Regulatory Point). On the right auricle, only the Laterality Point was stimulated (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe control group (CG) received sham auriculotherapy. In the absence of well-established sham protocols in the literature, random auricular points were gently touched with a pencil, without application of magnetic balls.[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] In both groups, the auricle was subsequently covered with gauze to maintain blinding of the patient, surgeon, and anesthesiologist involved in the procedure.\u003c/p\u003e \u003cp\u003eAfter 30 minutes all patients were transferred to the operating theatre, where they received a standard anesthesia protocol.\u003c/p\u003e \u003cp\u003eUnder multiparametric monitoring with non-invasive blood pressure measurement, 3-lead electrocardiogram, pulse oximetry, bispectral index (BIS\u0026trade; monitoring, Medtronic, CO, US) and neuromuscular transmission monitoring. Ringer Lactate solution was administered at an infusion rate of 8 ml/kg/h before induction of anesthesia, followed by an infusion of 2\u0026ndash;4 ml/kg/h intraoperatively. Target controlled infusion anesthesia (Alaris\u0026trade; PK Syringe Pump, Fresenius Kabi, Germany), was started with propofol at an effect site concentration of 6 \u0026micro;g/ml and remifentanil at 6 ng/ml, while intubation was facilitated by fentanyl 1 \u0026micro;g/kg and rocuronium bromide 0.6 mg/kg. The patient was then connected to mechanical ventilator settled to maintain EtCO\u003csub\u003e2\u003c/sub\u003e between 30 and 35 mmHg. Propofol infusion was decreased to an effect site concentration of 3\u0026ndash;4 \u0026micro;g/ml to maintain bispectral index between 40 and 60, while remifentanil was maintained at 4\u0026ndash;5 ng/ml. During surgical preparation patients received an initial low dose infusion of nitroglycerin at 0.1 \u0026micro;g/kg/min, titrated on a non-invasive MAP targeted between 60 and 70 mmHg, measured every 5 minutes.\u003c/p\u003e \u003cp\u003ePatients were withdrawn from the study in cases in the event of accidental removal of the gauze used to maintain patient blinding. All infusions were discontinued at the end of surgery, and following extubation, patients were transferred to the recovery room, where the auricles were uncovered and any adhesive materials removed. At the end of the procedure, the surgeon was asked to assess the quality of the surgical field in terms of bleeding using a 5-point Likert scale (1\u0026thinsp;=\u0026thinsp;Very Dissatisfied, 2\u0026thinsp;=\u0026thinsp;Dissatisfied, 3\u0026thinsp;=\u0026thinsp;Neutral/Unsure, 4\u0026thinsp;=\u0026thinsp;Satisfied, 5\u0026thinsp;=\u0026thinsp;Very Satisfied).\u003c/p\u003e \u003cp\u003ePostoperative monitoring was ensured for at least 30 minutes, after which patients were discharged to the ward.\u003c/p\u003e \u003cp\u003eOn the first postoperative day, MAP was measured to all patients by ward nurses during the morning round.\u003c/p\u003e\n\u003ch3\u003eOutcomes\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was the median intraoperative infusion rate of nitroglycerin, calculated as the total amount administered divided by patient body weight and duration of surgery, and expressed in \u0026micro;g/kg/min.\u003c/p\u003e \u003cp\u003eThe secondary outcome was the difference in MAP values between the two groups measured at predefined time points during the perioperative period: T0 (upon arrival in the preoperative holding area), T1 (before skin incision at steady-state drug concentration), T2 (30 minutes after anesthesia induction), T3 (at the end of surgery, before discontinuation of anesthesia), T4 (at discharge from the recovery room), and T5 (on the first postoperative day).\u003c/p\u003e \u003cp\u003eAn additional outcome was the surgeon\u0026rsquo;s qualitative assessment of the surgical field in terms of bleeding.\u003c/p\u003e \u003cp\u003eExploratory outcomes included differences in perioperative heart rate (HR), duration of surgery and anesthesia, cumulative doses of administered anesthetic drugs, and the occurrence of any complication before hospital discharge, assessed by reviewing in-hospital electronic medical records.\u003c/p\u003e\n\u003ch3\u003eSample size calculation /Statistical analysis\u003c/h3\u003e\n\u003cp\u003eGiven the exploratory nature of the study and the limited literature available on the topic, the study was designed as a pilot study and a formal sample size calculation was not performed. According to the rules of thumb proposed by Birkett and Day for pilot studies,[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] we therefore plan to enroll 20 patients per group, which is consistent with the number of cases typically observed at our clinical facility.\u003c/p\u003e \u003cp\u003eData are displayed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation, median (interquartile range, IQR) for numerical data or number of events (%) for categorical data. The normality distribution of numerical data was assessed with Shapiro-Wilk test and visually by histograms.\u003c/p\u003e \u003cp\u003eCategorical variables were evaluated with the Chi-square test or Fisher\u0026rsquo;s exact test in case of expected frequencies\u0026thinsp;\u0026lt;\u0026thinsp;5.\u003c/p\u003e \u003cp\u003eContinuous variables were compared with unpaired Student T-test with corresponding 95% confidence intervals, or using 2-sample Wilcoxon rank-sum test and Hodges\u0026ndash;Lehman estimation of location shift with corresponding asymptotic 95% CI in case of not normally distributed variables.\u003c/p\u003e \u003cp\u003eRepeated measures were analyzed using two-way repeated-measures analysis of variance (ANOVA), with post-hoc pairwise comparisons performed using the Bonferroni correction. A \u003cem\u003eP\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003cp\u003eSPSS version 15 (IBM Corporation, Chicago, IL, USA) for Windows (Microsoft Corporation, Redmond, WA, USA) and R (R Foundation for Statistical Computing) were used for data analysis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eBetween January and June 2024, 50 patients were screened for eligibility, 40 met the inclusion criteria and were randomized. Twenty patients were allocated to the auriculotherapy group (ATG) and 20 to the control group (CG). Final analysis was performed on 16 patients in the ATG and 17 in the CG (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). No significant differences were observed between the two cohorts with respect to demographic and clinical characteristics (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Anesthesia duration was comparable between the two groups (86 [IQR 77\u0026ndash;122] minutes in the ATG \u003cem\u003evs.\u003c/em\u003e 75 [IQR 60\u0026ndash;135] minutes in the CG, P\u0026thinsp;=\u0026thinsp;0.678. No adverse events related to the acupuncture technique were recorded.\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\u003eDemographic, medical and surgical characteristics of the study population (n\u0026thinsp;=\u0026thinsp;33)\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAuriculotherapy group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e46 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47 (19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (44)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e174 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e171 (11)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (13)\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=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eASA status\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (53)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eMedical history\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyslipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmokers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDepression/anxiety disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypothyroidism\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ-blockers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eACE inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalcium channel blockers\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStatins\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral hypoglycemic agents\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntidepressants/benzodiazepines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003e\u003cem\u003eIndication for FESS\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic sinusitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeviated nasal septum\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (29.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNasal polyposis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (29.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eData are displayed as n (%) or mean (standard deviation). ASA: American Society of Anesthesiologists. ACE: angiotensin converting enzyme. FESS: functional endoscopic sinus surgery.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\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\u003ePrimary, secondary and exploratory outcomes according to study group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAuriculotherapy Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;16)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eControl Group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e95% CI or median difference\u0026Dagger; (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\u003e\u003cem\u003ePrimary outcome\u003c/em\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\u003eNitroglycerin infusion rate, \u0026micro;g/kg/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.03 (0.01; 0.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.09 (0.04; 0.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.04 (-0.10 to -0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.043\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eSecondary outcomes\u003c/em\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\u003e\u003cb\u003eMean blood pressure, mmHg\u003c/b\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\u003e-T0: Upon arrival in the preoperative holding area\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (92; 114)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e98 (89; 104)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (-5 to 17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.279\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-T1: Before skin incision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-17 to 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.130\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-T2: 30 minutes after anesthesia induction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-5 to 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.446\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-T3: At end of surgery before discontinuation of anesthetic drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-3 to 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.297\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-T4: At discharge from the recovery room\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e103 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e99 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-4 to 13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.307\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-T5: On the first postoperative day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (95; 110)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e103 (98; 107)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (-6 to 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgeon\u0026rsquo;s assessment of the surgical field in terms of bleeding\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\u003eVery dissatisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.484\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDissatisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutral\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSatisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.688\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVery satisfied\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.622\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cem\u003eOther exploratory outcomes\u003c/em\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\u003e\u003cb\u003eHeart Rate, bpm\u003c/b\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\u003e-T0: Upon arrival in the preoperative holding area\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e74 (67; 81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e79 (69; 99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-5 (-17 to 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.551\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-T1: Before skin incision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e77 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-8 to 12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.670\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-T2: 30 minutes after anesthesia induction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-9 to 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.878\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e-T3: At end of surgery before discontinuation of anesthetic drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e76 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-6 to 13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.471\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery duration, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78 (55; 93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (43; 117)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (-28 to 42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.614\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnesthesia duration, min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e86 (77; 122)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (60; 135)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (-33 to 35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.678\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePropofol, mg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1021 (473)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e830 (406)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-123 to 506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.223\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRemifentanil, mcg/kg/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.11 (0.08; 0.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.14 (0.11; 0.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.02 (-0.07 to 0.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.366\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eComparison of randomized groups on primary and secondary outcomes. Data are presented as n (%), or median (interquartile range).\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eGroup difference is reported with corresponding 95% CI for normally distributed variables, or as median difference with 95% CI estimated using Hodges-Lehmann estimator. CI: Confidence Interval. \u003cem\u003eP\u003c/em\u003e value corresponded to \u003cem\u003et\u003c/em\u003e-test, Wilcoxon rank sum test, Chi-square or Fisher\u0026rsquo;s exact test.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eDrugs administration\u003c/h2\u003e \u003cp\u003eThe ATG required significantly lower doses of nitroglycerin to maintain MAP within the target range compared with the CG, with a median infusion rate of 0.03 [IQR 0.01\u0026ndash;0.07] \u0026micro;g/kg/min \u003cem\u003evs.\u003c/em\u003e 0.09 [IQR 0.04\u0026ndash;0.16] \u0026micro;g/kg/min, respectively (P\u0026thinsp;=\u0026thinsp;0.041). No statistically significant differences were observed between groups in the cumulative administered doses of anesthetic agents.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eHemodynamics\u003c/h3\u003e\n\u003cp\u003eHemodynamic variables were analyzed and compared between groups using repeated-measures analysis of variance. Compared to baseline values, MAP significantly decreased in both groups during surgery (P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and controlled hypotension was maintained for the entire procedural time.\u003c/p\u003e \u003cp\u003eAt discharge from the recovery room and on first postoperative day MAP was comparable to preoperative values in both groups (Fig.\u0026nbsp;3).\u003c/p\u003e \u003cp\u003eHR was not significantly different between the two groups at any time point.\u003c/p\u003e\n\u003ch3\u003eSurgical field quality assessment\u003c/h3\u003e\n\u003cp\u003eNo significant differences were reported in terms of qualitative assessment of the surgical field between the two cohorts.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe main finding of the present study is that a specific auricular acupuncture technique may be an effective complementary measure to modulate sympathetic nervous system activity, as reflected by a reduced requirement for nitroglycerin infusion to maintain mean arterial pressure within a safe target range during general anesthesia for functional endoscopic sinus surgery.\u003c/p\u003e \u003cp\u003eAcupuncture techniques have been increasingly incorporated into anesthetic practice for various therapeutic purposes. While their use is well established outside the operating room, intraoperative application remains limited, largely due to the scarcity of high-quality supporting evidence.[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Existing literature suggests that acupuncture can significantly reduce blood pressure in awake patients receiving antihypertensive therapy, although it is ineffective as a stand-alone treatment.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Several mechanisms of action have been proposed, including analgesic, autonomic, and neuroendocrine effects.[\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOur findings are consistent with previous reports on acupuncture, suggesting a potential synergistic interaction with nitroglycerin infusion. Although nitroglycerin is only one of several agents available for achieving controlled hypotension, we considered it the most suitable option for evaluating the intraoperative effects of auriculotherapy. Nitroglycerin-induced controlled hypotension has not been associated with reductions in cerebral oxygen saturation or postoperative cognitive dysfunction[\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] and it has been shown to preserve microvascular perfusion.[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] Moreover, its short half-life allows rapid titration to the target MAP, thereby minimizing the risk of bias in the analysis of the primary outcome.\u003c/p\u003e \u003cp\u003eNotably, the infusion rate of nitroglycerin required to achieve the target hemodynamic profile was significantly reduced in the treatment group, despite comparable anesthetic drug infusion dosages. This finding suggests the feasibility of an \u0026ldquo;acupuncture-drug balanced anesthesia\u0026rdquo; approach, where reduced drug consumption aligns with the multimodal strategies promoted by the ERAS protocols.[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Although our experience showed a direct hypotensive action of AT, it is unclear if this effect is synergistic or additive with nitroglycerin.\u003c/p\u003e \u003cp\u003eThe study design does not allow to clarify the underlying mechanisms of action, nor does it permit extrapolation of a similar interaction with other hypotensive agents.\u003c/p\u003e \u003cp\u003eThe mechanisms by which acupuncture lowers blood pressure remain incompletely understood. Current evidence suggests that its hypotensive effects may be mediated through multiple pathways, including modulation of the autonomic nervous system, cardiovascular regulatory centers, and the renin\u0026ndash;angiotensin\u0026ndash;aldosterone system. Auricular acupuncture appears to have a favorable safety profile, with most reported adverse events being mild and transient.[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe hypotensive effect of auriculotherapy appeared to be negligible in the postoperative period, as MAP values at discharge from the recovery room and on the first postoperative day were comparable to preoperative levels. One possible explanation is the short duration of action of AT, combined with the lower intraoperative exposure to nitroglycerin in the treatment group. Moreover, auriculotherapy is typically administered as a chronic intervention,[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] whereas in the present study it was limited to the intraoperative period.\u003c/p\u003e \u003cp\u003eThe loss of efficacy observed in the early postoperative period supports the hypothesis that AT may play an adjunctive role when used in combination with other therapies; however, this interpretation is speculative and warrants further investigation. Nevertheless, postoperative hemodynamics data was not associated with safety concerns, and standard monitoring protocols appeared sufficient to ensure safe patient recovery and discharge.\u003c/p\u003e \u003cp\u003eIn our sample, AT did not show any effects on heart rate, which remained comparable between groups throughout the study period. Moreover, the nitroglycerin doses required in both groups did not result in clinically relevant tachycardia, a known common side effect that could limit the use of nitroglycerin.\u003c/p\u003e \u003cp\u003eAs expected, the quality of the surgical field was similar between groups. Intraoperative bleeding appeared to be primarily related to MAP values, irrespective of the method used to achieve the hypotensive target. This finding is consistent with previous literature demonstrating that controlled hypotension improves surgical conditions during FESS regardless of the agent or technique employed.[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAlthough adverse events related to auricular acupuncture\u0026mdash;such as auricular hematoma, local erythema and swelling, headache, and palpitations\u0026mdash;have been reported in the literature,[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] no technique-related adverse events were observed in our study population, supporting the safety profile of the technique.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study has several limitations. First of all, the small sample size limits generalizability of the results. Moreover, in the absence of established evidence, the selection of auricular acupoints and the duration of magnetic ball application were based on clinical practice. Future research should compare different acupoint combinations to identify the most effective treatment strategy. In addition, the control group received sham auriculotherapy, which is not yet standardized across acupuncture trials. Although our findings are promising, they require validation in larger and more diverse patient populations and should be replicated using alternative hypotensive agents.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eAuriculotherapy may exert an independent hypotensive effect in patients undergoing functional endoscopic sinus surgery reducing pharmacological requirements for maintenance of controlled hypotension; however, its efficacy appears to be limited to the intraoperative period.\u003c/p\u003e \u003cp\u003eAlthough the underlying mechanism of action remains unclear, its integration into a multimodal perioperative strategy within ERAS protocols may help optimize the balance between therapeutic benefits and risks while promoting faster recovery. Future studies should further investigate the potential role of acupuncture as a stand-alone intervention and explore whether repeated applications could allow for a more sustained blood pressure control.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eASA American Society of Anesthesiologists\u003c/p\u003e\n\u003cp\u003eAT auriculotherapy\u003c/p\u003e\n\u003cp\u003eATG auriculotherapy group\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBMI body mass index\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCG control group\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCONSORT Consolidated Standards of Reporting Trials\u003c/p\u003e\n\u003cp\u003eERAS Enhanced Recovery After Surgery\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eFESS functional endoscopic sinus surgery\u003c/p\u003e\n\u003cp\u003eMAP mean arterial pressure\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eAvailability of data and materials:\u003c/em\u003e The data that support the findings of this study are available on request from the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding:\u003c/em\u003e Support was provided solely from institutional and/or departmental sources.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests:\u003c/em\u003e No potential conflict of interest relevant to this article was reported.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthics approval and consent to participate:\u003c/em\u003e It was approved on December 7, 2023 by the Institutional Ethics Committee (Comitato Etico Territoriale Lazio Area 3 (ID number: 5828). This research accomplishes with all the international requirements for ethics in research.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eClinical trial registration number:\u003c/em\u003e Clinicaltrial.gov (NCT06182982), Principal investigator: Fabio Sbaraglia, Date of registration: December 13, 2023).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFS CM DDP conceived this study; CM DDP performed auricolo and sham therapy; CTC DMM operated as blinded anesthesiologist and provided data entry; SS managed data entry; FS GS wrote the first draft of the manuscript; CM AP e GS edited first draft; GS AP performed the statistical analyses. MR RM JG edited and revised final manuscript. All authors revised the manuscript critically. All have given their final approval of the version to be published.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eZhang J, Liu L, Zhu M, et al. Research Status and Prospects of Acupuncture in Perioperative Medicine Over the Past Decade: A Bibliometric Analysis. J Pain Res. 2023;16:2189\u0026ndash;2204.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLu Z, Dong H, Wang Q, Xiong L. Perioperative acupuncture modulation: more than anaesthesia. Br J Anaesth. 2015;115(2):183\u0026ndash;93.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang Y, Ji H, Lu Y, et al. Sedative-sparing effect of acupuncture in gastrointestinal endoscopy: systematic review and meta-analysis. Front Med (Lausanne). 2023;10:1189429.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSbaraglia F, Piersanti A, Riso C, et al. Evidences and perspective of acupuncture techniques in perioperative setting within the context of Enhanced Recovery After Surgery, AME Medical Journal 2025 (online first) doi: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.21037/amj-24-37\u003c/span\u003e\u003cspan address=\"10.21037/amj-24-37\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi DZ, Zhou Y, Yang YN, et al. Acupuncture for essential hypertension: a meta-analysis of randomized sham-controlled clinical trials. Evid Based Complement Alternat Med. 2014:279478\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang W, Zhang M, Han Y, Liu Y, Liu Y, Sun C. Combined acupuncture-medicine anesthesia used in thyroid surgery: A systematic review and meta-analysis. Medicine (Baltimore). 2023;102(1):e32582.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang JW, Ye Y, Wang XR, et al. Acupuncture attenuates renal sympathetic activity and blood pressure via beta-adrenergic receptors in spontaneously Hypertensive Rats. Neural Plast. 2017;2017:18696402\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi P, Tjen-A-Looi SC. Mechanism of the inhibitory effect of electroacupuncture on experimental arrhythmias. J Acupunct Meridian Stud. 2013;6(2):69\u0026ndash;81\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWu Q, Mo YC, Huang LP, Luo L, Wang JL. Effect of transcutaneous acupoint electrical stimulation on stress in brain surgery with propofol target controlled infusion general anesthesia. Chin J Integr Tradit West Med 2013;33:1621\u0026ndash;1625.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGao J, Chen G, He H, et al. The effect of auricular therapy on blood pressure: A systematic review and meta-analysis. Eur J Cardiovasc Nurs. 2020;19(1):20\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim B, Park H. The effects of auricular acupressure on blood pressure, stress, and sleep in elders with essential hypertension: a randomized single-blind sham-controlled trial. Eur J Cardiovasc Nurs. 2023 5;22(6):610\u0026ndash;619.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarak M, Yoav L, Abu el-Naaj I. Hypotensive anaesthesia versus normotensive anaesthesia during major maxillofacial surgery: A review of the literature. ScientificWorldJournal. 2015;2015:480728.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDegoute CS. Controlled hypotension: A guide to drug choice. Drugs. 2007;67:1053\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNogier R. History of Auriculotherapy: Additional Information and New Developments. Med Acupunct. 2021;33(6):410\u0026ndash;419.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlimi D, Chelly JE. New universal nomenclature in auriculotherapy. J Altern Complement Med. 2018;24(1):7\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNguyen H, Lee DY, Wu HM, Hsieh CL. Auricular acupuncture to lower blood pressure involves the adrenal gland in spontaneously hypertensive rats. Evid Based Complement Alternat Med Nov 20:2020:3720184.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuo K, Lu Y, Wang X, et al. Multi-level exploration of auricular acupuncture: from traditional Chinese medicine theory to modern medical application. Front Neurosci. 2024;18:1426618.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eQi XZ. Clinical study of auricular pressure combined with drugs in the treatment of hypertension. Hebei Medicine 2014;20: 839\u0026ndash;841.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa P, Liu X, Liu Z, et al. The SHARE: SHam Acupuncture REporting guidelines and a checklist in clinical trials J Evid Based Med 2023;16(4):428\u0026ndash;431.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBirkett MA, Day SJ. Internal pilot studies for estimating sample size. Stat Med. 1994;13(23\u0026ndash;24):2455\u0026ndash;2463.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang Y, Ji H, Lu Y, et al. Sedative-sparing effect of acupuncture in gastrointestinal endoscopy: systematic review and meta-analysis. Front Med (Lausanne) 2023;10:1189429\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou W, Longhurst JC. Neuroendocrine mechanisms of acupuncture in the treatment of hypertension. Evid Based Complement Alternat Med 2012;2012:878673.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChoi SH, Lee SJ, Jung Y-S, et all. Nitroglycerin- and Nicardipine-induced hypotension does not affect cerebral oxygen saturation and postoperative cognitive function in patients undergoing Orthognathic surgery. J Oral Maxillofac Surg. 2008;66:2104\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCorr\u0026ecirc;a TD, Filho RR, Assun\u0026ccedil;\u0026atilde;o MSC, Silva E, Lima A. Vasodilators in septic shock resuscitation: a clinical perspective. Shock. 2017;47:269\u0026ndash;75.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLima A, van Genderen ME, van Bommel J, Klijn E, Jansem T, Bakker J. Nitroglycerin reverts clinical manifestations of poor peripheral perfusion in patients with circulatory shock. Crit Care. 2014;18:R126\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRossi M, Tritapepe L, Monzani R, et al. Enhanced recovery after surgery and the role of the anesthetist, road to implementation. Minerva Anestesiol. 2025 May 8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShen MY, Lou QY, Liu S, et al. The efficacy and safety of auricular acupoint therapy on treating functional dyspepsia with insomnia: study protocol for a randomized controlled trial. Front Med (Lausanne). 2025;12:1496502.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim B, Park H. The effects of auricular acupressure on blood pressure, stress, and sleep in elders with essential hypertension: a randomized single-blind sham-controlled trial. Eur J Cardiovasc Nurs. 2023;22(6):610\u0026ndash;619.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eB\u0026auml;umler P, Zhang W, St\u0026uuml;binger T, et al. Acupuncture-related adverse events: systematic review and meta-analyses of prospective clinical studies. BMJ Open 2021;11:e045961.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-anesthesia-analgesia-and-critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Anesthesia, Analgesia and Critical Care](https://janesthanalgcritcare.biomedcentral.com/)","snPcode":"44158","submissionUrl":"https://submission.nature.com/new-submission/44158/3","title":"Journal of Anesthesia, Analgesia and Critical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Anesthesia, Acupuncture, Auriculotherapy, Nitroglycerin, Total Intravenous Anesthesia, Controlled Hypotension","lastPublishedDoi":"10.21203/rs.3.rs-9105769/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9105769/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAdministration of hypotensive drugs is common to induce controlled hypotension during surgery but dose-dependent side effects could limit their use. The primary hypothesis of our study is that the application of magnetic ball-plasters for auriculotherapy could be effective in achieving a hypotensive effect during general anesthesia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSingle-center, randomized controlled trial conducted in Italy between June and July \u003cbr\u003e\n2024 and involving adult patients undergoing functional endoscopic sinus surgery (FESS). Magnetic ball plasters for auriculotherapy were applied to the treatment group (ATG), while a sham auriculotherapy was simulated for the control group (CG). Both groups received intravenous anesthesia with propofol and remifentanil and a continuous infusion of nitroglycerin was ensured to maintain a mean arterial pressure (MAP) between 60 and 70 mmHg. The primary outcome was the median intraoperative infusion rate of nitroglycerin, calculated as the total amount administered divided by patient body weight and duration of surgery. Secondary outcomes were: difference in MAP values between the two groups measured at predefined time points during the perioperative period and on first postoperative day; surgeon’s qualitative assessment of the surgical field in terms of bleeding.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong 50 patients enrolled, 40 were randomized and final analysis was completed on a sample of 33 patients. The ATG required lower doses of nitroglycerin compared with the CG to maintain MAP within target range, with a median infusion rate of 0.03 [IQR 0.01-0.07] μg/kg/min \u003cem\u003evs.\u003c/em\u003e 0.09 [IQR 0.04-0.16] μg/kg/min, respectively (P=0.041). Compared to baseline values, MAP significantly decreased in both groups during surgery (P \u0026lt;0.001), and controlled hypotension was maintained for the entire procedural time. At discharge from the recovery room and on first postoperative day MAP was comparable to preoperative values in both groups. No significant differences were reported in terms of qualitative assessment of the surgical field between the two cohorts.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this randomized controlled trial auriculotherapy was effective in maintaining a hypotensive status during general anesthesia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial registration: \u003c/strong\u003eClinicaltrial.gov (NCT06182982), Principal investigator: Fabio Sbaraglia, Date of registration: December 13, 2023).\u003c/p\u003e","manuscriptTitle":"Auriculotherapy for controlled hypotension during functional endoscopic surgery of the paranasal sinuses under general anesthesia: AuriFESS, a feasibility randomized pilot study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-07 10:18:41","doi":"10.21203/rs.3.rs-9105769/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-05-15T17:12:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-15T12:40:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-29T07:06:18+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"309403596929652793644250773694065964576","date":"2026-04-23T06:05:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"50976868554183614579095527944939226739","date":"2026-04-22T13:23:25+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-07T17:26:52+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-05T21:12:02+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"77859941309849739268949910638797707321","date":"2026-04-02T10:11:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"70760675692925244792674769084032084929","date":"2026-04-01T18:22:52+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-01T09:06:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-31T08:09:16+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-31T08:08:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Anesthesia, Analgesia and Critical Care","date":"2026-03-12T14:01:45+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-anesthesia-analgesia-and-critical-care","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Journal of Anesthesia, Analgesia and Critical Care](https://janesthanalgcritcare.biomedcentral.com/)","snPcode":"44158","submissionUrl":"https://submission.nature.com/new-submission/44158/3","title":"Journal of Anesthesia, Analgesia and Critical Care","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"69bad42f-3f21-41ee-be0b-166aff71387f","owner":[],"postedDate":"April 7th, 2026","published":true,"recentEditorialEvents":[{"type":"decision","content":"Revision requested","date":"2026-05-15T17:12:42+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-15T12:40:35+00:00","index":22,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-15T17:23:49+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-07 10:18:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9105769","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9105769","identity":"rs-9105769","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}