Effect of Opioid-free Analgesia and Anesthesia on the Quality of Postoperative Recovery and Nausea Vomit in Obese Patients Receiving Laparoscopic Sleeve Gastrectomy: a study protocol for a prospective randomized controlled trial

Effect of Opioid-free Analgesia and Anesthesia on the Quality of Postoperative Recovery and Nausea Vomit in Obese Patients Receiving Laparoscopic Sleeve Gastrectomy: a study protocol for a prospective randomized controlled trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effect of Opioid-free Analgesia and Anesthesia on the Quality of Postoperative Recovery and Nausea Vomit in Obese Patients Receiving Laparoscopic Sleeve Gastrectomy: a study protocol for a prospective randomized controlled trial JiaQi Tong, HaiJun Hou, BiJia Song, Lei Wan This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5476305/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background : Anesthesia for obese patient and postoperative pain management remains a big challenge. Their greater demand for opioids comes with both acute and long-term adverse effects，is calling for opioid-free anaesthetic strategies. Opioid-free anesthesia(OFA) is a multimodal anesthesia associating hypnotics, N-methyl-D-aspartate antagonists, local anesthetics, anti-inflammatory drugs and α-2 agonists to realize enhanced recovery after surgery(ERAS). With further research, we have confirmed that OFA is safe and feasible for laparoscopic surgery. However，how to select and combine the application of alternative drugs, need to be carefully selected. Therefore, the formulation of OFA programs and strategies plays a crucial role in ensuring effective suppression of surgical stress and reducing potential adverse reactions and complications of multi-drug combination. Methods : This prospective double-blind, randomized ,controlled clinical trial will incorporate 76 patients scheduled for laparoscopic sleeve gastrectomy(LGS) surgery. The eligible population will be 1:1 randomly assigned to OFA or conventional anesthesia group. Primary endpoint was the 15-item recovery quality scale score after surgery. Discussion : This trial explores the efficacy of opioid-free anesthesia in obesity patients, it provides more superior scheme than conventional one,which using opioid drugs . If OFA achieves positive results in this experiment, it will bring support for the promotion of OFA.It’s not only accelerate postoperative recovery ,but also improve patient satisfaction. Trial Registration : This trial registered at clinical trials.gov (NCT06305221) on 12 March 2024 (https://register.clinicaltrials.gov/prs/app/action/SelectProtocol). opioid-free anesthesia laparoscopic surgery postoperative recovery postoperative nausea and vomiting Figures Figure 1 Figure 2 Background The prevalence of obesity is on the rise and now exceeds 60% 1 worldwide. The incidence of overweight and obesity in Chinese adults is about 46% 2 . Obesity and its related complications not only reduce people's quality of life, affect the mental state of patients,but also increase the social medical burden, known as the immortal cancer. After years of practice and development, bariatric metabolic surgery has now become the "gold standard" for the treatment of metabolic diseases such as obesity 3 . In recent years, as people's understanding of health continues to change, the number of bariatric surgery has also increased by years. Studies have found that bariatric surgery can benefits to weight loss long-term , help patients control blood sugar, reduce the risk of cardiovascular disease and incidence of other comorbidities,as well as significantly reduce the overall mortality of obese patients and the occurrence of related diseases 4 .Laparoscopic gastric bypass (LRYGB) and LSG are widely used compared with other surgical methods for weight loss 5 . LSG creates a sleeve stomach along the greater curvature of the stomach, reduces stomach capacity, and utilizes the endocrine regulation mechanism of the stomach to reduce body mass, thereby alleviating metabolic syndrome. Due to its simple operation precedure, few complications, positive effect on weight loss and alleviating metabolic related diseases, it has become the most common operation way of bariatric surgery 6-8 . Nevertheless, there is a certain probability that the following complications may occur, such as gastric leakage, bleeding, gastroesophageal reflux disease, postoperative nausea and vomiting (PONV) 9 . PONV is the most common adverse reaction of LSG, with an incidence of up to 80% 10,11 . At the same time, it is worth noting that obesity has a great impact on the respiratory and circulatory system, which will reduce the patients' cardiopulmonary reserve capacity and the body's compensatory capacity, which poses a major challenge to the anesthesia and postoperative management of obese patients. Opioids are an important part of general anesthesia and perioperative analgesia. Perioperative application of opioids is associated with postoperative nausea and vomiting, excessive sedation, intestinal obstruction and other adverse reactions.What’s more, postoperative hypoxemia, hyperalgesia, chronic pain and cognitive impairment 12 are more serious and long-term complications. The residual effect of opioids is the main factor of early postoperative hypoxemia,which is trigger for death and brain damage 13 . Moreover, the comorbidities related to obesity can have an amplified effect with opioid-related complications, making postoperative pain management in obese patients to be an unique challenge 14 . Due to the large weight of obese patients and their own pathophysiological reasons, their demand for opioids is greater, so higher risk of adverse complications after surgery come as follow. In addition, opioids can cause dose-dependent hypersensitivity and tolerance, leading to more severe postoperative pain and ultimately contributing to postoperative chronic pain 15,16 . Thus, effective multimodal analgesia and anesthesia protocols are fundamental to the success of ERAS. These multimodal combination regimens are designed to accelerate postoperative recovery by reducing postoperative pain, intraoperative and postoperative opioid dosage, and opioid-related adverse reactions. At present, the effectiveness of OFA has been validated in patients undergoing abdominal and pelvic surgery 17 . OFA is a combination of several narcotic drugs and/or anesthetic techniques, including N-methyl-D-aspartate(NMDA) receptor antagonists, local anesthetics, anti-inflammatory drugs, and alpha-2 adrenergic receptor agonists,which can facilitate high quality general anesthesia with hemodynamic stability 18 . Although previous studies have confirmed that OFA is safe and feasible for LGS surgery, there is great heterogeneity in how to select and combine anti-harm drugs to replace opioids 19- 21 . Therefore, the formulation of OFA strategies it’s necessary to be identified to not only ensure effective suppression of surgical stress, but also reduce potential adverse reactions and complications of multi-drug combination. Methods Objectives and design The OFA study is a prospective double-blind, randomized, controlled clinical trial, and will be conducted at the Department of Anaesthesiology, Beijing Friendship Hospital, Capital Medical University.76 patients scheduled to undergo elective LGS surgery will beallocated 1:1 to receive either a standard anesthesia protocol or an OFA, comparing the quality of postoperative recovery and nausea vomit. Only providing with informed written consent, patients who meet the eligibility or exclusion criteria were admitted to the study.The flowchart of this study is shown in Fig. 1. Randomization and Blinding In preparation for the trial,random numbers will be generated randomly by a computer according to the sample size. The random code will be stored in sealed opaque envelopes and kept with anesthesia nurse. Before the patient entry the operation room on the day of the operation ,nurse hands one of the envelopes to the anesthesiologist A who administered the anesthesia and collected the data(not responsible for postoperative data collection). If the number is odd number,then the patient is assigned to no opioid anesthesia and analgesia group (OFA, OFA group) ,or the another,to conventional opioid anesthesia and analgesia group(OBA, OBA group). Anesthesiologist B responsible for postoperative follow-up,surgeon, and the patient himself were not aware of the grouping. In the middle stage of this clinical study, if an emergency or some serious complications occur, considered may be related to the intervention of the trail,then sealed envelope will be opened.At the same time, it will be recorded and reported to the Data Monitoring Committee (DMC) and principal investigators. Anesthesiologists and surgeons will make diagnosis and take action to guarantee the safety of subjects for free. The schedule of the enrolment and the assessments is presented in the Standard Protocol Items: Recommendations for Interventional Trials figure (Figs. 2).Fig.2 Standard protocol items: recommendations for interventional trials schedule of enrollment, intervention and assessments. GA:general anesthesia TAP:transversus abdominis plane PACU:post-anesthesia care unit QoR-15:global score Quality of Recovery-15 scale OFA:opioid-free analgesia OBA:opioid anesthesia Study population We will recruit 76 patients who are scheduled to undergo LSG in Beijing Friend- ship Hospital affiliated to Capital Medical University.Trial site investigators will identify consecutive eligible patients from the listed criteria. Eligible patients will receive written and oral information,after that they will be included after investigators obtained informed written consent. Included patients should meet the following criteria: 1.adult patients aged 18–65 years who plan to undergo LSG 2.American Society of Anesthesiologists (ASA) physical status I–II. 3.Body mass index (BMI) >30kg/m 2 4.provision of signed informed consent. The exclusion criteria are as follows: 1.chronic pain 2.severe liver dysfunction (total bilirubin 2 mg dl -1 ) 3.severe renal dysfunction (glomerular filtration rate 60mL min-1 1.73m -2 ) 4.pregnancy or lactation 5.preoperative heart rate <50 beats/min, sick sinus syndrome, severe heart block; 6.dementia or significant neurological disease (such as stroke, epilepsy, intracranial tumors, Parkinson's disease ) 7.alcohol or drug abuse Discharge criteria are as follows: 1.participant have so serious adverse reactions during the study that it is impossible to continue 2.the operation time was more than 8 hours or the bleeding was more than 300ml 3.other reasons that warrant discontinuation from the study as determined by the researcher; 4.participant or their legal representative request for discontinuation during the study period or withdrawal of consent. Standard anesthesia procedure After entering the operating room, patients will receive a routine monitoring including electrocardiogram (ECG), heart rate (HR), non-invasive blood pressure (NIBP), pulse oxygen saturation (SpO 2 ), and depth of anesthesia monitoring (BIS). After peripheral venous access was opened ,all patients receive radial artery puncture under local anesthesia to monitor invasive blood pressure. 1. Intravenous Induction of General Anesthesia Prior to general anesthesia, all patients were received intravenous dexamethasone 10mg for postoperative nausea and vomiting prophylaxis, flurbiprofen axetil 50mg for preemptive analgesia. In OFA group, patients were premedicated with IV dexmedetomidine hydrochloride (1μg·kg -1 )lasting for 10 minutes before intubation. All patients received the following for anesthesia induction: midazolam 2mg, propofol 2mg·kg -1 ,and rocuronium 0.6-1mg·kg -1 . Esketamine 0.5mg·kg -1 or sufentanil 0.3-0.5μg·kg -1 were administered as analgesics of induction in group OFA and group OBA, respectively. Then intubated 3 minutes later. 2. Ultrasound-Guided Transversus Abdominis Plane Block The ultrasound probe was placed in the axial plane on the midaxillary line, scan the abdomen between the subcostal margin and the iliac crest. Under the guidance of the ultrasound, the three layers of abdominal wall muscles are visualized:the external oblique muscle, the internal oblique muscle as well as the transversus abdominis muscles.The target is the bright white fascia transversalis,, between the internal oblique muscle and the transversus abdominis muscles.The two-dimensional probe of the ultrasound instrument was wrapped in sterile gloves, disinfected and covered with sterile towels surrounding the border of the procedural field. Identify the ultrasound probe in the correct position and the fascia of the transverse abdominal muscle was well exposed, then insert nerve stimulation needle, advanced until it reached the transversus abdominis plane (TAP) and inject 20ml 0.375% ropivacaine slowly and incrementally after blood and air were not withdrawn .We will see the TAP will begin to "unzip" in fusiform. The contralateral operation was the same, and bilateral transverse abdominal muscle fascia block was completed. 3. Maintenance of General Anesthesia l In OFA group, intravenous continuous infusion of propofol, the mixture of esketamine and dexmedetomidine hydrochloride(esketamine 50mg + dexmedetomidine 150ug + 0.9%saline into 50mL) 0.1mL/kg/h-0.2mL/kg/h targeted to a BIS number of 40-60. Intermittent rocuronium was added 10-20mg/ time to maintain muscle relaxation. After the commencement of the operation, Supplemental dosing of 0.1mg/kg esketamine was added according to hemodynamic parameters.The injection of the mixture of esketamine and dexmedetomidine was stopped 40min prior to the end of surgery.Troisetron 5mg and flurbiprofen 50mg were injected before the end of the operation, and propofol was stopped at the end of skin closure. l In OBA group: The patients will receive intravenous propofol and remifentanil to maintain the BIS number of 40-60,and rocuronium 10–20mg/time to maintain muscle relaxation. During the operation, added 10-20μg sufentanil everytime according to hemodynamic parameters. Troisetron 5mg and flurbiprofen 50mg were injected before the end of the operation. Propofol and remifentanil were stopped at the end of skin closure. After the surgery, muscle relaxant antagonists (intravenous atropine 0.5mg and neostigmine 1mg) to antagonize any residual neuromuscular blockade, remove endotracheal intubation until patient restored spontaneous respiration and the muscle strength was fully recovered. 4.Postoperative Analgesia Treatment Both groups patients were transferred to a post-anesthesia care unit (PACU) ,and received continuous monitoring of vital signs from anesthesiologist and nurse who are blinded to group assignment. If necessary, titrate sufentanil 2.5-5μg intravenously until numerical rating scale(NRS)score≤3.When Aldrete score≥9 meets requirement, patients will be allowed to return to the wards. In wards, the patients in both groups received patient-controlled intravenous analgesia (PCIA) device as well as intravenous flurbiprofen axidate (50mg/ time) twice daily in the morning and evening .If pain scores NRS were evaluated higher than 4, flurbiprofen axetil 50mg and meperidine hydrochloride 50mg or morphine hydrochloride 10mg was used as rescue analgesia. Study endpoints Primary Outcome Measure The 15-item recovery quality scale at 24h before surgery and 24h, 48h after surgery (global score Quality of Recovery-15 scale, QoR-15) 22 . Secondary Outcomes Measures Dosage of postoperative analgesics in 48 hours after surgery : record dosage of postoperative analgesics Duration of until postoperative PACU Aldrete score> 9 points in 30 min after surgery at postoperative recovery room : Anesthesia recovery was defined by Aldrete's recovery score (RS, 0-10), assessed following postanesthesia care unit (PACU) arrival, with RS ≥9 considered discharge eligible anesthesia-related complication in 24 hours after surgery : record anesthesia-related complication time to first exhaust gas after surgery in 24 hours after surgery time of first postoperative mobilization in 24 hours after surgery Overall benefit of analgesic score satisfaction (OBAS) 23 in pain treatment in 6, 24, 48 hours after surgery : To calculate the OBAS score, compute the sum of scores in items 1-6 and add '4-score in item 7'. Note that a low score indicates high benefit. test overall benefit of analgesic score satisfaction in pain treatment at 6, 24, 48 hours after surgery Acute pain numeric rating scale score in 6, 24, 48 hours after surgery : The pain 0-10 classification is the numerical classification (NRS) of subjective assessment, with 0 painless pain, 1-3 mild pain, 4-6 moderate pain, 7-9 severe pain, and 10 severe pain. test acute pain numeric rating scale score at 6, 24, 48 hours after surgery Rhodes Index of Nausea, Vomiting, and Retching 24,25 in one night before surgery : Rhodes Index of Nausea, Vomiting, and Retching, an 8-item questionnaire, to measure the incidence and severity of nausea, vomiting, and retching At each timepoint, a total Rhodes score was calculated from the sum of the 8 RINVR questions. Total Rhodes scores were compared at 6 different timepoints as well as overall across all 6 time points. record Nausea and vomiting, the Rhodes index score Rhodes Index of Nausea, Vomiting, and Retching in 6, 24, 48 hours after surgery : Rhodes Index of Nausea, Vomiting, and Retching, an 8-item questionnaire, to measure the incidence and severity of nausea, vomiting, and retching. At each timepoint, a total Rhodes score was calculated from the sum of the 8 RINVR questions. Total Rhodes scores were compared at 6 different timepoints as well as overall across all 6 timepoints. record Nausea and vomiting, the Rhodes index score. record Nausea and vomiting, the Rhodes index score. Adverse effects During surgery, Patients with bradycardia(heart rate less than 50 beats/min), intravenous atropine 0.5mg or ephedrine 5 to 10mg ; if tachycardia (heart rate more than 100 beats/min), intravenous esmolol 10-20 mg; Patients with hypertension ( blood pressure increased by more than 20% of the basic value), intravenous 5 ~ 10mg urapidil on the premise of ensuring the depth of anesthesia; if hypotension (blood pressure decreased by more than 20% of the basic value), intravenous methoxamine 5mg or ephedrine 5-10mg. All adverse reactions related to interventions will be recorded during the entire trial period. Vital signs (body temperature, breathing, blood pressure and heart rate), laboratory examinations (blood, urine and stool routine, liver and kidney function) and adverse events (bradycardia,tachycardia,hypertension,hypotension) are all needed to be collected and monitored. The development of all adverse reactions will also be observed and receive close personal supervision until the adverse reactions disappear.The associated costs arising therefrom will be provided in accordance with hospital regulations. Data collection and monitoring First, before the start of this experiment, the outcome assessors and investigators will receive systematic training on the use of these questionnaires to avoid subjective bias as much as possible. Second, the original data will be collected using the printed case report forms (CRF) and double entered into the electronic case report form (eCRF) by independent researchers timely.Third, the analysis indicators include objective indicators such as the time to first out-of-bed mobilization,and the total amount of analgesic needed. Forth，the researchers should take measures to control the incidence rate of drop-out within 15%. An independent trained monitor will supervise the correctness of data management. In case of data missing, analyses will be performed according to the principle of intention-to-treatment.The monitor, statistician ,scientific research manager and an anesthetist joined together to form the DMC.The DMC, independent from the sponsor and competing interests, oversees the safety and ethical normativity of the overall implementation process of this trial and decides whether the test needs to be adjusted or terminated. The original data and results will be submitted to DMC every 2 months. Research data will be securely stored for 5 years, and will not be shared and disclosed to unauthorised individuals until published. Sample size calculation Based on our pre-experimental results, the standard deviation (SD) of the overall QoR-15 score 24 hours after surgery in the OFA group and the OBA group was 11.2 and 7.6, respectively, and difference of 6 points in the QoR-15 score indicated clinically significant differences 26 . Assuming α=0.05 and β=0.1, the subjects in this study will be allocated to the two groups at a 1:1 ratio,70 patients are required , allowing for possible 10% sample drop rate,total sample size will be 76 (38 per each group). Statistical analysis Statistical analyses will be presented using SPSS 23.0 and GraphPad Prism 6.0 software. Continuous variables will be described by mean ± standard deviation(SD) and median (interquartile range), to be compared by Student’s t-test or Mann-Whitney U-test. Categorical variables will be reported as frequency (percentage) and compared by Pearson’s chi-squared test or Fisher’s exact test.The primary outcome QoR-15 score will be evaluated via the Student’s t-test or Mann-Whitney U-test (after the normality test). Intraoperative data, lengh of until postoperative PACU , duration of Aldrete score >9 points, pain NRS score, OBAS score and Rhodes Index of Nausea and Vomiting at 6h 24h and 48h after surgery, time to first out-of-bed mobilization, total amount of postoperative analgesic will be compared between the two groups using Student’s T-test or Mann–Whitney U-test (after the normality test). Anesthesia-related complication will be analysed between the two groups using Chi-square test or Fisher’s exact test. Discussion With the rapid development of the social economy and changes in people's living lifestyles, the incidence of obesity is rapidly increasing. Obesity is often accompanied with metabolism related complications such as type 2 diabetes, hypertension, obstructive sleep apnea syndrome, arthritis and polycystic ovary, which is one of the important chronic diseases affecting people's physical and mental health 27,28 .At present, the most effective treatment for obesity and related metabolic diseases is bariatric surgery. LSG is a highly valued surgical way from metabolic surgeons worldwide in recent years due to its simple procedure and good short-term efficacy 29 .In addition to reducing body weight, it also has therapeutic effect on obesity related metabolic diseases such as type 2 diabetes, hyperlipidemia, nonalcoholic fatty liver, etc 30 .The most important mission during the perioperative period of bariatric surgery is preventing the surgical complications. Postoperative discomfort mainly comes from pain, including gastrointestinal spasms and incision. Postoperative pain can produce long-lasting negative effects on the endocrine system, central nervous system, immune system, cardiovascular system, digestive system, etc. Thereby , translated into neuroendocrine signals, the result is an increased blood pressure, increased heart rate, increased gastric acid secretion, decreased immune function, emotional anxiety and depression. These consequences will all have an adverse effect on early exercise, delaying recovery, and even leading to the occurrence of complications. Currently, opioid drugs are the most widely used type of analgesic in clinic, due to their powerful analgesic effect and long duration. Except its positive effect, adverse reactions such as respiratory depression, nausea and vomiting, hyperalgesia, immune suppression and skin itching also occur as adverse complications 31 .Respiratory suppression is one of the most serious adverse reactions, especially to those with severe obesity and obstructive sleep apnea hypopnea syndrome 32 .In addition, bariatric surgery has a high incidence of postoperative nausea and vomiting in obese patients, opioid drugs can directly act on receptors in the brainstem chemical trigger area, exacerbating the occurrence of perioperative nausea and vomiting ,seriously affecting patient recovery 33 . Therefore, under the premise of effective pain relief, it’s important to integrate multiple non-opioid drugs and technologies to minimize the use of opioid drugs and their adverse effects in obese patients 34 . The safety and feasibility of OFA have been validated in various surgeries such as gynecological surgery 35 , thoracic surgery 36 etc. Based on the clinical characteristics of LSG, this trial developed OFA via using TAP combined with esketamine and dexmedetomidine to reduce postoperative pain, nausea and vomiting, and other complications, promoting postoperative recovery and reducing the incidence and severity of chronic pain. The drug doses selected in our study were all within the safe range according to our preliminary experiments, which has confirmed the effectiveness of the drug doses. The OFA study is a prospective double-blind, randomized controlled clinical trial evaluating the impact of OFA on severe postoperative opioid related adverse events. The OFA scheme for LSG may have the following advantages in accelerating postoperative rehabilitation: 1. The incidence of adverse reactions related to opioid drugs, such as hypoxemia and PONV, will be significantly reduced, ensuring the safety and comfort of patients. 2. The valid perioperative analgesic effect of TAP, combined with the improvement effect of postoperative cognitive function of esketamine and dexmedetomidine can prevent postoperative neurocognitive disorder. Meanwhile, it has the potential to reduce chronic pain, promote rapid recovery. However, there are currently no relevant research reports. Although the feasibility of OFA has been validated in different types surgeries, its clinical application is still controversial, and there are currently many advocates for the application of OFA only in small and medium-sized surgeries.The limitations of this study are as follows： 1.These questionnaire are mostly obtained through patients own description, so the results tend to be biased towards subjective ratings of pain impressions by patients. Therefore, they may not directly measure the analgesic effect, leading to subjective bias. Therefore, before the start of this experiment, the visiting personnel received systematic training on the use of these questionnaires to avoid subjective bias as much as possible. Of course, the analysis indicators also include objective indicators such as the time to first out-of-bed mobilization, and the total amount of analgesic needed. 2.This experiment is a small sample, single center study, and there is possible individual heterogeneity in obese patients. In the future, prospective trials with multiple centers and large samples are still expected to verify. Overall, for obese patients, OFA seems to be superior to conventional schemes using opioid drugs , which can accelerate postoperative recovery and improve patient satisfaction. If OFA achieves positive results in this experiment, it will bring support for the promotion of OFA. OFA can not only reduce adverse reactions such as respiratory suppression, but also shorten hospitalization time, reduce medical costs, and save medical resources. However ,OFA is not without challenges,it is unclear whether OFA is beneficial and can improve the long-term prognosis of patients, and further research is needed. Trial status This is protocol version 1.4 refined on 2024.01.25. This trial has been approved on 8 February 2024 by the Institutional Review Board of Beijing Friendship Hospital of Capital Medical University (2024-P2-004-02). Written informed consent will be obtained from all study participants.The trial started recruiting patients in March 2024 after registered on the clinicaltrials.gov(NCT06305221),and the recruiting period will last 12 months，ending in March 2025 approximately. Abbreviations ERAS enhanced recovery after surgery OFA opioid-free analgesia LSG laparoscopic sleeve surgery NMDA N-methyl-D-aspartate QoR-15 15-item recovery quality scale LRYGB Laparoscopic gastric bypass PONV postoperative nausea and vomiting ASA American Society of Anesthesiologists BMI body mass index OBA opioid anesthesia TAP transversus abdominis plane PACU post-anesthesia care unit NRS Numeric Rating Scale PCIA patient-controlled intravenous analgesia OBAS overall benefit of satisfaction CRF case report forms DMC Data Monitoring Committee Declarations Ethical approval and consent to participate Our research is conducted in accordance with the principles of the Declaration of Helsinki. Prior to starting, ethical approval have been obtained for all protocols from the clinicaltrials.gov. This trial has been approved by the Institutional Review Board of Beijing Friendship Hospital of Capital Medical University (2024-P2-004-02) on 8 February 2024. Written informed consent will be obtained from all study participants. In the process of this trial ,if we make some important modifications,such as changes to eligibility criteria, outcomes, analyses ,sample sizes,study procedures,etc,we will apply for approval to the local medical ethical committee.Meanwhile ,all study participants will be notified, informed consent will be requested again when necessary. And online trail registries in ClinicalTrials.gov will be updated. The results of this research will be published in international journals. Consent for publication Not applicable — no identifying images、videos and other personal details relating to participants included in this trial . Availability of data and materials The datasets used, information materials of the participants during the experiment and informed consent forms are available from the corresponding author on reasonable request. ( Lei Wan, Email [email protected] ) Competing interests The authors report no conflicts of interest in this work. Funding This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors'. Authors' contributions WL is responsible for supervising the clinical study .TJQ and SBJ conceived the idea and designed this trial. TJQ and HHJ are responsible for the recruitment and treatment of participants. SBJ is responsible for the statistical analysis. This manuscript was drafted by TJQ and revised by WL. All authors read and approved the final manuscript. Acknowledgements I would like to express my heartfelt thanks to all staff in the general surgical department of Beijing Friendship Hospital, Capital Medical University. All authors will acknowledge all the participants in this study. References Batchelder AJ, Williams R, Sutton C. et a1.Tlle evolution of minimally invasive bariatric surgery[J]. J Surg Res. 2013;183(2):559–66. Wang Y, Wang L. Qu W.New national data show alarming increase in obesity and noncommunicable chronic diseases in China[J]. Eur J Clin Nutr. 2017;71(1):149–50. Ponce J, DeMaria EJ, Nguyen NT. et a1.American Society for Metabolic and Bariatric Surgery estimation of bariatric surgery procedures in 201 5 and surgeon workforce in the United States[J]. Surg Obes Relat Dis. 2016;12(9):1637–9. Christou NV, Sampalis JS, Liberman M. et a1.Surgery decreases long—term mortality,morbidity,and health care use in morbidly obese patients[J]. Ann Surg. 2004;240(3):416–discussion423423. Angrisani L, Santonicola A, Iovino P. et a1.Reply to LeRer to the Editor: Bariatric Surgery Worldwide 20 1 3 Reveals a Rise in Mini—Gastric. Bypass[J] Obes Surg. 2015;25(1 1):2166–8. Angrisani L, Santonicola A, Iovino P, et al. Bariatric Surgery Worldwide 2013[J]. Obes Surg. 2015;25(10):1822–32. Khorgami Z, Shoar S, Andalib A, et al. Trends in utilization of bariatric surgery, 2010–2014: sleeve gastrectomy dominates[J]. Surg Obes Relat Dis. 2017;13(5):774–8. Rosenthal RJ, Diaz AA, Arvidsson D, et al. International Sleeve Gastrectomy Expert Panel Consensus Statement: best practice guidelines based on experience of > 12, 000 cases[J]. Surg Obes Relat Dis. 2012;8(1):8–19. Frezza EE, Reddy S, Gee LL, et al. Complications after sleeve gastrectomy for morbid obesity[J]. ObesSurg. 2009;19(6):684–7. Gan TJ, Diemunsch P, Habib AS, et al. Consensus guidelines for the management of postoperative nausea and vomiting[J]. Anesth Analg. 2014;118(1):85–113. Bataille A, Letourneulx JF, Charmeau A, et al. Impact of a prophylactic combination of dexamethasone-ondansetron on postoperative nausea and vomiting in obese adult patients undergoing laparoscopic sleeve gastrectomy during closed-loop propofol-remifentanil anaesthesia: a randomised double-blind placebo-controlled study[J]. Eur J Anaesthesiol. 2016;33(12):898–90. Beloeil H, Laviolle B, Menard C, et al. POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery [J]. BMJ Open. 2018;8(6):e020873. Lee LA, Caplan RA, Stephens LS, et al. Postoperative opioid-induced respiratory depression: a closed claims analysis [J]. Anesthesiology. 2015;122(3):659–65. Hollander SW, Sifft A, Hess S. et a1.Identifying the Bariatric Patient at Risk for Pulmonary Embolism: Prospective Clinical Using Duplex Sonography and Blood Screening[J].Obes Surg, 2015, 25(11):2011–7. Lavand'Homme P, Steyaert A. Opioid-free anesthesia opioid side effects: Tolerance and hyperalgesia [J]. Best Pract Res Clin Anaesthesiol. 2017;31(4):487–98. Weinbroum AA. Postoperative hyperalgesia-A clinically applicable narrative review [J]. Pharmacol Res. 2017;120:188–205. Baboli KM, Liu H, Poggio JL. Opioid-free postoperative analgesia: Is it feasible? [J]. Curr Probl Surg. 2020;57(7):100794. Wei W, ZhangA, Liu L, et al. Effects of subanaesthetic S-ketamine on postoperative delirium and cognitive function in elderly patients undergoing non-cardiac thoracic surgery: a protocol for a randomised, double-blinded, placebo-controlled and positive-controlled, non-inferiority trial (SKED trial) [J]. BMJ Open. 2022;12(8):e061535. Larue A, Jacquet-Lagreze M, Ruste M, et al. Opioid-free anaesthesia for video-assisted thoracoscopic surgery: A retrospective cohort study with propensity score analysis [J]. Anaesth Crit Care Pain Med. 2022;41(4):101089. Selim J, Jarlier X, Clawier T, et al. Impact of Opioid-free Anesthesia After Video-assisted Thoracic Surgery: A Propensity Score Study [J]. Ann Thorac Surg. 2022;114(1):218–24. An G, Zhang Y, Chen N, et al. Opioid-free anesthesia compared to opioid anesthesia for lung cancer patients undergoing video-assisted thoracoscopic surgery: A randomized controlled study [J]. PLoS ONE. 2021;16(9):e0257279. Stark PA, Myles PS, Berke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15 [J]. Anesthesiology. 2013;118(6):1332–40. Lehmann N, Joshi GP, Dirkmann D, et al. Development and longitudinal validation of the overall benefit of analgesia score: a simple multi-dimensional quality assessment instrument. Br J Anaesth. 2010;105(4):511–8. 10.1093/bja/aeq186 . Kushner BS, Freeman D, Sparkman J, Salles A, Eagon JC, Eckhouse SR. Assessment of postoperative nausea and vomiting after bariatric surgery using a validated questionnaire. Surg Obes Relat Dis. 2020;16(10):1505–13. Lehmann N, Joshi GP, Dirkmann D, et al. Development and longitudinal validation of the overall benefit of analgesia score: a simple multi-dimensional quality assessment instrument [J]. Br J Anaesth. 2010;105(4):511–8. Myles PS, Myles DB. An Updated Minimal Clinically Important Difference for the QoR-15 Scale. Anesthesiology. 2021;135(5):934–5. 10.1097/ALN.0000000000003977 . Seeberg KA, Borgeraas H, Hoffo D, et al. Gastric By⁃ pass Versus Sleeve Gastrectomy in Type 2 Diabetes:Effects on Hepatic Steatosis and Fibrosis:A Randomized Controlled Trial [J]. Ann Intern Med. 2022;175(1):74–83. Aminian A, Wilson R, Al⁃Kurd A, et al. Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity[J]. JAMA. 2022;327(24):2423–33. Fouse T, BrethauerS. Resolution of comorbidities and impact on longevity following bariatric and metabolic surgery [J]. Sury Clin North Am. 2016;96:717–32. Pories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it?an operation proves to be the most effective therapy for adult—onset diabetes mellitus[J]. Ann Surg. 1995;222:339–50. Koepke EJ, Manning EL, Miller TE et al. The rising tide of opioid use and abuse:The role of the anesthesiologist[ J]. Perioper Med (Lond),2018,7:16. Trotta M, Ferrari C, D'Alessandro G, et al. Enhanced recovery after bariatric surgery (ERABS) in a high-volume bariatric center[J].SurgObes. Relat Dis. 2019;15:1785–92. Andrews PLR. Physiology of nausea and vomiting[J]. Br J Anesth. 1992;69(7 Suppl 1):S2–19. Ibrahim M, Elnabtity AM, Hegab A, et al. Combined opioid free and loco-regional anaesthesia enhances the quality of recovery in sleeve gastrectomy done under ERAS protocol: a randomized controlled trial [J]. BMC Anesthesiol. 2022;22(1):29. 10.1186/s12871-021-01561-w . Zheng Z, Cheng W, Li L et al. Effect of opioid-free anesthesia on postoperative nausea and vomiting after gynecological surgery: a systematic review and meta-analysis.[J].Frontiers in pharmacology,2023,14:1330250. 10.3389/fphar.2023.1330250 Bello M, Oger S, Bedon -Carte S, et al. Effect of opioid -free anaesthesia on postoperative epidural ropivacaine requirement after thoracic surgery:a retrospective un- matched case -control study[J]. Anaesth Crit Care Pain Med. 2019;38(5):499–505. Supplementary Files Informedconsent.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5476305","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":485571578,"identity":"73b37d7b-b257-4373-b7ef-4b835fd5b264","order_by":0,"name":"JiaQi Tong","email":"","orcid":"","institution":"Capital Medical University Affiliated Beijing Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"JiaQi","middleName":"","lastName":"Tong","suffix":""},{"id":485571579,"identity":"7c207f94-3dbb-49c8-b717-b5c4c059e100","order_by":1,"name":"HaiJun Hou","email":"","orcid":"","institution":"China Academy of Traditional Chinese Medicine Guanganmen Hospital: China Academy of Chinese Medical Sciences Guang'anmen Hospital","correspondingAuthor":false,"prefix":"","firstName":"HaiJun","middleName":"","lastName":"Hou","suffix":""},{"id":485571580,"identity":"479d3552-8210-436a-8ca2-4180e6f06863","order_by":2,"name":"BiJia Song","email":"","orcid":"","institution":"Capital Medical University Affiliated Beijing Friendship Hospital","correspondingAuthor":false,"prefix":"","firstName":"BiJia","middleName":"","lastName":"Song","suffix":""},{"id":485571581,"identity":"ca741cbd-7b3d-4363-bf57-92d9ef686efb","order_by":3,"name":"Lei Wan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvklEQVRIie3PIQuDQBjG8VcGS4JV2fAbDB4RLupXmazKWFw03crAuk9iPjFYNqwHV0xLhkWDYbI4GHe2hfvl98/DS2RZ/8kRBCKPnMK8+SRBsSyZQZieo30I8TpVadw1vB8pCXe6MdyP+/oGtWIyu0RXOsRMN8dEjsaFWjPpcN8lkVXapBvQTFBuXNY8mIwSOa8QlA/K+MZoJZUD6isUfDknWxj8EpR51I+TSr2yfQbDOQm1yRcsO7csy7J+eANNZUVGP9SoUwAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-4120-7393","institution":"Capital Medical University Affiliated Beijing Friendship Hospital","correspondingAuthor":true,"prefix":"","firstName":"Lei","middleName":"","lastName":"Wan","suffix":""}],"badges":[],"createdAt":"2024-11-18 13:09:46","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5476305/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5476305/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":87272952,"identity":"511a0a6d-aed9-4024-87c1-0fdaf590e884","added_by":"auto","created_at":"2025-07-22 08:33:46","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":170629,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5476305/v1/eb6ec3c5eef5329449f569b0.png"},{"id":87272162,"identity":"927ef34f-a6d8-40bc-a992-82ebddf2907e","added_by":"auto","created_at":"2025-07-22 08:25:46","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":78969,"visible":true,"origin":"","legend":"\u003cp\u003eStandard protocol items: recommendations for interventional trials schedule of enrollment, intervention and assessments.\u003c/p\u003e\n\u003cp\u003eGA:general anesthesia TAP:transversus abdominis plane PACU:post-anesthesia care unit QoR-15:global score Quality of Recovery-15 scale OFA:opioid-free analgesia OBA:opioid anesthesia\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5476305/v1/916e324fd919594095e84d1e.png"},{"id":93092577,"identity":"b60c776b-a085-4a35-96e4-7bb2fe1083f5","added_by":"auto","created_at":"2025-10-09 02:52:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1298385,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5476305/v1/9e30835d-d446-458a-ad42-45c490991819.pdf"},{"id":87272166,"identity":"9c6b8551-d278-46ff-a009-6f910717fed2","added_by":"auto","created_at":"2025-07-22 08:25:46","extension":"docx","order_by":4,"title":"","display":"","copyAsset":false,"role":"supplement","size":35874,"visible":true,"origin":"","legend":"","description":"","filename":"Informedconsent.docx","url":"https://assets-eu.researchsquare.com/files/rs-5476305/v1/98fdd863c3001111fdfa9b58.docx"}],"financialInterests":"","formattedTitle":"Effect of Opioid-free Analgesia and Anesthesia on the Quality of Postoperative Recovery and Nausea Vomit in Obese Patients Receiving Laparoscopic Sleeve Gastrectomy: a study protocol for a prospective randomized controlled trial","fulltext":[{"header":"Background","content":"\u003cp\u003eThe prevalence of obesity is on the rise and now exceeds 60%\u003csup\u003e1\u0026nbsp;\u003c/sup\u003eworldwide. The incidence of overweight and obesity in Chinese adults is about 46%\u003csup\u003e2\u003c/sup\u003e. Obesity and its related complications not only reduce people\u0026apos;s quality of life, affect the mental state of patients,but also increase the social medical burden, known as the immortal cancer.\u003c/p\u003e\n\u003cp\u003eAfter years of practice and development, bariatric metabolic surgery has now become the \u0026quot;gold standard\u0026quot; for the treatment of metabolic diseases such as obesity\u003csup\u003e3\u003c/sup\u003e. In recent years, as people\u0026apos;s understanding of health continues to change, the number of bariatric surgery has also increased by years. Studies have found that bariatric surgery can benefits to weight loss long-term , help patients control blood sugar, reduce the risk of cardiovascular disease and incidence of other comorbidities,as well as significantly reduce the overall mortality of obese patients and the occurrence of related diseases\u003csup\u003e4\u003c/sup\u003e.Laparoscopic gastric bypass (LRYGB) and LSG are widely used compared with other surgical methods for weight loss\u003csup\u003e5\u003c/sup\u003e. LSG creates a sleeve stomach along the greater curvature of the stomach, reduces stomach capacity, and utilizes the endocrine regulation mechanism of the stomach to reduce body mass, thereby alleviating metabolic syndrome. Due to its simple operation precedure, few complications, positive effect on weight loss and alleviating metabolic related diseases, it has become the most common operation way of bariatric surgery\u003csup\u003e6-8\u003c/sup\u003e. Nevertheless, there is a certain probability that the following complications may occur, such as gastric leakage, bleeding, gastroesophageal reflux disease, postoperative nausea and vomiting (PONV)\u003csup\u003e9\u003c/sup\u003e. PONV is the most common adverse reaction of LSG, with an incidence of up to 80%\u003csup\u003e10,11\u003c/sup\u003e. At the same time, it is worth noting that obesity has a great impact on the respiratory and circulatory system, which will reduce the patients\u0026apos; cardiopulmonary reserve capacity and the body\u0026apos;s compensatory capacity, which poses a major challenge to the anesthesia and postoperative management of obese patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOpioids are an important part of general anesthesia and perioperative analgesia. Perioperative application of opioids is associated with postoperative nausea and vomiting, excessive sedation, intestinal obstruction and other adverse reactions.What\u0026rsquo;s more, postoperative hypoxemia, hyperalgesia, chronic pain and cognitive impairment\u003csup\u003e12\u0026nbsp;\u003c/sup\u003eare more serious and long-term complications. The residual effect of opioids is the main factor of early postoperative hypoxemia,which is trigger for death and brain damage\u003csup\u003e13\u003c/sup\u003e. Moreover, the comorbidities related to obesity can have an amplified effect with opioid-related complications, making postoperative pain management in obese patients to be an unique challenge\u003csup\u003e14\u003c/sup\u003e. Due to the large weight of obese patients and their own pathophysiological reasons, their demand for opioids is greater, so higher risk of adverse complications after surgery come as follow. In addition, opioids can cause dose-dependent hypersensitivity and tolerance, leading to more severe postoperative pain and ultimately contributing to postoperative chronic pain\u003csup\u003e15,16\u003c/sup\u003e. Thus, effective multimodal analgesia and anesthesia protocols are fundamental to the success of ERAS.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese multimodal combination regimens are designed to accelerate postoperative recovery by reducing postoperative pain, intraoperative and postoperative opioid dosage, and opioid-related adverse reactions. At present, the effectiveness of OFA has been validated in patients undergoing abdominal and pelvic surgery\u003csup\u003e17\u003c/sup\u003e. OFA is a combination of several narcotic drugs and/or anesthetic techniques, including N-methyl-D-aspartate(NMDA) receptor antagonists, local anesthetics, anti-inflammatory drugs, and alpha-2 adrenergic receptor agonists,which can facilitate high quality general anesthesia with hemodynamic stability\u003csup\u003e18\u003c/sup\u003e.\u0026nbsp;Although previous studies have confirmed that OFA is safe and feasible for LGS surgery, there is great heterogeneity in how to select and combine anti-harm drugs to replace opioids\u003csup\u003e19-\u003c/sup\u003e\u003csup\u003e21\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTherefore, the formulation of OFA strategies it\u0026rsquo;s necessary to be identified to not only ensure effective suppression of surgical stress, but also reduce potential adverse reactions and complications of multi-drug combination.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e\u003cstrong\u003eObjectives and design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe OFA study is a prospective double-blind, randomized, controlled clinical trial, and will be conducted at the Department of Anaesthesiology, Beijing Friendship Hospital, Capital Medical University.76 patients scheduled to undergo elective LGS surgery will beallocated 1:1 to receive either a standard anesthesia protocol or an OFA, comparing the quality of postoperative recovery and nausea vomit. Only providing with informed written consent, patients who meet the eligibility or exclusion criteria were admitted to the study.The flowchart of this study is shown in Fig. 1.\u003c/p\u003e\n\u003ch3\u003eRandomization and Blinding\u003c/h3\u003e\n\u003cp\u003eIn preparation for the trial,random numbers will be generated randomly by a computer according to the sample size.\u0026nbsp;The random code will be stored in sealed opaque envelopes and kept with anesthesia nurse. Before the patient entry the operation room on the day of the operation ,nurse hands one of the envelopes to the anesthesiologist A who administered the anesthesia and collected the data(not responsible for postoperative data collection). If the number is odd number,then the patient is assigned to no opioid anesthesia and analgesia group (OFA, OFA group)\u0026nbsp;,or the another,to conventional opioid anesthesia and analgesia group(OBA, OBA group).\u0026nbsp;Anesthesiologist B responsible for postoperative follow-up,surgeon, and the patient himself were not aware of the grouping. In the middle stage of this clinical study, if an emergency or some serious complications occur, considered may be related to the intervention of the trail,then sealed envelope will be opened.At the same time, it will be recorded and reported to the Data Monitoring Committee (DMC) and principal investigators. Anesthesiologists and surgeons will make diagnosis and take action to guarantee the safety of subjects for free.\u003c/p\u003e\n\u003cp\u003eThe schedule of the enrolment and the assessments is presented in the Standard Protocol Items: Recommendations for Interventional Trials figure (Figs. 2).Fig.2 Standard protocol items: recommendations for interventional trials schedule of enrollment, intervention and assessments.\u003c/p\u003e\n\u003cp\u003eGA:general anesthesia \u0026nbsp; TAP:transversus abdominis plane \u0026nbsp; PACU:post-anesthesia care unit \u0026nbsp; QoR-15:global score Quality of Recovery-15 scale \u0026nbsp;OFA:opioid-free analgesia \u0026nbsp;OBA:opioid anesthesia \u0026nbsp;\u003c/p\u003e\n\u003ch3\u003eStudy population\u003c/h3\u003e\n\u003cp\u003eWe will recruit 76 patients who are scheduled to undergo LSG in Beijing Friend- ship Hospital affiliated to Capital Medical University.Trial site investigators will identify consecutive eligible patients from the listed criteria. Eligible patients will receive written and oral information,after that they will be included after investigators obtained informed written consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eIncluded patients should meet the following criteria:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.adult patients aged 18\u0026ndash;65 years who plan to undergo LSG\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.American Society of Anesthesiologists (ASA) physical status I\u0026ndash;II.\u003c/p\u003e\n\u003cp\u003e3.Body mass index (BMI) \u0026gt;30kg/m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003e4.provision of signed informed consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe exclusion criteria are as follows:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.chronic pain\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e2.severe liver dysfunction (total bilirubin 2 mg dl\u003csup\u003e-1\u003c/sup\u003e)\u003c/p\u003e\n\u003cp\u003e3.severe renal dysfunction (glomerular filtration rate 60mL min-1 1.73m\u003csup\u003e-2\u003c/sup\u003e)\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e4.pregnancy or lactation\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e5.preoperative heart rate \u0026lt;50 beats/min, sick sinus syndrome, severe heart block;\u003c/p\u003e\n\u003cp\u003e6.dementia or significant neurological disease (such as stroke, epilepsy, intracranial tumors, Parkinson\u0026apos;s disease )\u003c/p\u003e\n\u003cp\u003e7.alcohol or drug abuse\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDischarge criteria are as follows:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e1.participant have so serious adverse reactions during the study that it is impossible to continue\u003c/p\u003e\n\u003cp\u003e2.the operation time was more than 8 hours or the bleeding was more than 300ml\u003c/p\u003e\n\u003cp\u003e3.other reasons that warrant discontinuation from the study as determined by the researcher;\u003c/p\u003e\n\u003cp\u003e4.participant or their legal representative request for discontinuation during the study period or withdrawal of consent.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStandard anesthesia procedure\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAfter entering the operating room, patients will receive a routine monitoring including\u0026nbsp;electrocardiogram (ECG), heart rate (HR), non-invasive blood pressure (NIBP), pulse oxygen saturation (SpO\u003csub\u003e2\u003c/sub\u003e), and depth of anesthesia monitoring (BIS).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAfter peripheral venous access was opened\u0026nbsp;,all patients receive radial artery puncture under local anesthesia to monitor invasive blood pressure.\u003c/p\u003e\n\u003ch3\u003e1. Intravenous Induction of General Anesthesia\u0026nbsp;\u003c/h3\u003e\n\u003cp\u003ePrior to general anesthesia, all patients were received intravenous dexamethasone 10mg for postoperative nausea and vomiting prophylaxis, flurbiprofen axetil 50mg for preemptive analgesia. In OFA group, patients were premedicated with IV dexmedetomidine hydrochloride (1\u0026mu;g\u0026middot;kg\u003csup\u003e-1\u0026nbsp;\u003c/sup\u003e)lasting for 10 minutes before intubation. All patients received the following for anesthesia induction: midazolam 2mg, propofol 2mg\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e,and rocuronium 0.6-1mg\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e. Esketamine 0.5mg\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e or sufentanil 0.3-0.5\u0026mu;g\u0026middot;kg\u003csup\u003e-1\u003c/sup\u003e were administered as analgesics of induction in group OFA and group OBA, respectively. Then intubated 3 minutes later.\u003c/p\u003e\n\u003cp\u003e2. \u003cstrong\u003eUltrasound-Guided Transversus Abdominis Plane Block\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe ultrasound probe was placed in the axial plane on the midaxillary line, scan the abdomen between the subcostal margin and the iliac crest. Under the guidance of the ultrasound, the three layers of abdominal wall muscles are visualized:the external oblique muscle, the internal oblique muscle as well as the transversus abdominis muscles.The target is the bright white fascia transversalis,, between the internal oblique muscle and the transversus abdominis muscles.The two-dimensional probe of the ultrasound instrument was wrapped in sterile gloves, disinfected and covered with sterile towels surrounding the border of the procedural field. Identify the ultrasound probe in the correct position and the fascia of the transverse abdominal muscle was well exposed, then insert nerve stimulation needle, advanced until it reached the transversus abdominis plane\u0026nbsp;(TAP)\u0026nbsp;and inject 20ml 0.375% ropivacaine slowly and incrementally after blood and air were not withdrawn .We will see the TAP will begin to \u0026quot;unzip\u0026quot; in fusiform. The contralateral operation was the same, and bilateral transverse abdominal muscle fascia block was completed.\u003c/p\u003e\n\u003ch3\u003e3. Maintenance of General Anesthesia\u003c/h3\u003e\n\u003cp\u003el In OFA group, intravenous continuous infusion of propofol, the mixture of esketamine and dexmedetomidine hydrochloride(esketamine 50mg + dexmedetomidine 150ug + 0.9%saline into 50mL) 0.1mL/kg/h-0.2mL/kg/h targeted to a BIS number of 40-60. Intermittent rocuronium was added 10-20mg/ time to maintain muscle relaxation. After the commencement of the operation, Supplemental dosing of 0.1mg/kg esketamine was added according to hemodynamic parameters.The injection of the mixture of esketamine and dexmedetomidine was stopped 40min prior to the end of surgery.Troisetron 5mg and flurbiprofen 50mg were injected before the end of the operation, and propofol was stopped at the end of skin closure.\u003c/p\u003e\n\u003cp\u003el In OBA group: The patients will receive intravenous propofol and remifentanil to maintain the BIS number of 40-60,and rocuronium 10\u0026ndash;20mg/time to maintain muscle relaxation. During the operation, added 10-20\u0026mu;g sufentanil everytime according to hemodynamic parameters. Troisetron 5mg and flurbiprofen 50mg were injected before the end of the operation. Propofol and remifentanil were stopped at the end of skin closure.\u003c/p\u003e\n\u003cp\u003eAfter the surgery, muscle relaxant antagonists (intravenous atropine 0.5mg and neostigmine 1mg) to antagonize any residual neuromuscular blockade, remove endotracheal intubation until patient restored spontaneous respiration and the muscle strength was fully recovered.\u003c/p\u003e\n\u003ch3\u003e4.Postoperative Analgesia Treatment\u003c/h3\u003e\n\u003cp\u003eBoth groups patients were transferred to a post-anesthesia care unit (PACU) ,and received continuous monitoring of vital signs from anesthesiologist and nurse who are \u0026nbsp; blinded to group assignment. If necessary, titrate sufentanil 2.5-5\u0026mu;g intravenously until numerical rating scale(NRS)score\u0026le;3.When Aldrete score\u0026ge;9 meets requirement, patients will be allowed to return to the wards.\u003c/p\u003e\n\u003cp\u003eIn wards, the patients in both groups received patient-controlled intravenous analgesia (PCIA) device as well as intravenous flurbiprofen axidate (50mg/ time) twice daily in the morning and evening .If pain scores NRS were evaluated higher than 4, flurbiprofen axetil 50mg and meperidine hydrochloride 50mg or morphine hydrochloride 10mg was used as rescue analgesia.\u0026nbsp;\u003c/p\u003e\n\u003ch4\u003eStudy endpoints\u003c/h4\u003e\n\u003ch4\u003ePrimary Outcome Measure\u003c/h4\u003e\n\u003cp\u003eThe 15-item recovery quality scale at 24h before surgery and 24h, 48h after surgery (global score Quality of Recovery-15 scale, QoR-15)\u003csup\u003e22\u003c/sup\u003e.\u003c/p\u003e\n\u003ch4\u003eSecondary Outcomes Measures\u003c/h4\u003e\n\u003cul\u003e\n \u003cli\u003e\u003cstrong\u003e\u003cem\u003eDosage of postoperative analgesics in 48 hours after surgery\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u0026nbsp;\u003c/em\u003erecord dosage of postoperative analgesics\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u003cem\u003eDuration of until postoperative PACU Aldrete score\u0026gt; 9 points in 30 min after surgery at postoperative recovery room\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Anesthesia recovery was defined by Aldrete\u0026apos;s recovery score (RS, 0-10), assessed following postanesthesia care unit (PACU) arrival, with RS \u0026ge;9 considered discharge eligible\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u003cem\u003eanesthesia-related complication in 24 hours after surgery\u003c/em\u003e\u003c/strong\u003e: record anesthesia-related complication\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u003cem\u003etime to first exhaust gas after surgery in 24 hours after surgery\u003c/em\u003e\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u003cem\u003etime of first postoperative mobilization in 24 hours after surgery\u003c/em\u003e\u003c/strong\u003e\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u003cem\u003eOverall benefit of analgesic score satisfaction\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;(OBAS)\u003csup\u003e23\u003c/sup\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;in pain treatment in 6, 24, 48 hours after surgery\u003c/em\u003e\u003c/strong\u003e: To calculate the OBAS score, compute the sum of scores in items 1-6 and add \u0026apos;4-score in item 7\u0026apos;. Note that a low score indicates high benefit. test overall benefit of analgesic score satisfaction in pain treatment at 6, 24, 48 hours after surgery\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u003cem\u003eAcute pain numeric rating scale score in 6, 24, 48 hours after surgery\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u0026nbsp;\u003c/em\u003eThe pain 0-10 classification is the numerical classification (NRS) of subjective assessment, with 0 painless pain, 1-3 mild pain, 4-6 moderate pain, 7-9 severe pain, and 10 severe pain. test acute pain numeric rating scale score at 6, 24, 48 hours after surgery\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u003cem\u003eRhodes Index of Nausea, Vomiting, and Retching\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u003csup\u003e24,25\u003c/sup\u003e\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;in one night before surgery\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u003c/em\u003e Rhodes Index of Nausea, Vomiting, and Retching, an 8-item questionnaire, to measure the incidence and severity of nausea, vomiting, and retching At each timepoint, a total Rhodes score was calculated from the sum of the 8 RINVR questions. Total Rhodes scores were compared at 6 different timepoints as well as overall across all 6 time points. record Nausea and vomiting, the Rhodes index score\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003e\u003cem\u003eRhodes Index of Nausea, Vomiting, and Retching in 6, 24, 48 hours after surgery\u003c/em\u003e\u003c/strong\u003e\u003cem\u003e:\u0026nbsp;\u003c/em\u003eRhodes Index of Nausea, Vomiting, and Retching, an 8-item questionnaire, to measure the incidence and severity of nausea, vomiting, and retching. At each timepoint, a total Rhodes score was calculated from the sum of the 8 RINVR questions. Total Rhodes scores were compared at 6 different timepoints as well as overall across all 6 timepoints. record Nausea and vomiting, the Rhodes index score. record Nausea and vomiting, the Rhodes index score.\u003c/li\u003e\n\u003c/ul\u003e\n\u003cp\u003e\u003cstrong\u003eAdverse effects\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eDuring surgery, Patients with bradycardia(heart rate less than 50 beats/min), intravenous atropine 0.5mg or ephedrine 5 to 10mg ; if tachycardia (heart rate more than 100 beats/min), intravenous esmolol 10-20 mg; Patients with hypertension\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e( blood pressure increased by more than 20% of the basic value), intravenous 5 ~ 10mg urapidil on the premise of ensuring the depth of anesthesia; if hypotension\u003c/p\u003e\n\u003cp\u003e(blood pressure decreased by more than 20% of the basic value), intravenous methoxamine 5mg or ephedrine 5-10mg.\u003c/p\u003e\n\u003cp\u003eAll adverse reactions related to interventions will be recorded during the entire trial period. Vital signs (body temperature, breathing, blood pressure and heart rate), laboratory examinations (blood, urine and stool routine, liver and kidney function) and adverse events (bradycardia,tachycardia,hypertension,hypotension) are all needed to be collected and monitored. The development of all adverse reactions will also be observed and receive close personal supervision until the adverse reactions disappear.The associated costs arising therefrom will be provided in accordance with hospital regulations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData collection and monitoring\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFirst, before the start of this experiment, the outcome assessors and investigators will receive systematic training on the use of these questionnaires to avoid subjective bias as much as possible. Second, the original data will be collected using the printed case report forms (CRF) and double entered into the electronic case report form (eCRF) by independent researchers timely.Third, the analysis indicators include objective indicators such as the time to first out-of-bed mobilization,and the total amount of analgesic needed. Forth，the researchers should take measures to control the incidence rate of drop-out within 15%. An independent trained monitor will supervise the correctness of data management. In case of data missing, analyses will be performed according to the principle of intention-to-treatment.The monitor, statistician ,scientific research manager and an anesthetist joined together to form the DMC.The DMC, independent from the sponsor and competing interests, oversees the safety and \u0026nbsp;ethical normativity of the overall implementation process of this trial and decides whether the test needs to be adjusted or terminated. The original data and results will be submitted to DMC every 2 months. Research data will be securely stored for 5 years, and will not be shared and disclosed to unauthorised individuals until published.\u003c/p\u003e\n\u003ch3\u003eSample size calculation\u003c/h3\u003e\n\u003cp\u003eBased on our pre-experimental results, the standard deviation (SD) of the overall QoR-15 score 24 hours after surgery in the OFA group and the OBA group was 11.2 and 7.6, respectively, and difference of 6 points in the QoR-15 score indicated clinically significant differences\u003csup\u003e26\u003c/sup\u003e. Assuming \u0026alpha;=0.05 and \u0026beta;=0.1, the subjects in this study will be allocated to the two groups at a 1:1 ratio,70 patients are required , \u0026nbsp;allowing for possible 10% sample drop rate,total sample size will be 76 (38 per each group).\u003c/p\u003e\n\u003ch3\u003eStatistical analysis\u0026nbsp;\u003c/h3\u003e\n\u003cp\u003eStatistical analyses will be presented using SPSS 23.0 and GraphPad Prism 6.0 software. Continuous variables will be described by mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation(SD) and median (interquartile range), to be compared by Student\u0026rsquo;s t-test or Mann-Whitney U-test. Categorical variables will be reported as frequency (percentage) and compared by Pearson\u0026rsquo;s chi-squared test or Fisher\u0026rsquo;s exact test.The primary outcome QoR-15 score will be evaluated via the Student\u0026rsquo;s t-test or Mann-Whitney U-test (after the normality test). Intraoperative data, lengh of until postoperative PACU , duration of Aldrete score \u0026gt;9 points, pain NRS score, OBAS score and Rhodes Index of Nausea and Vomiting at 6h 24h and 48h after surgery, time to first out-of-bed mobilization, total amount of postoperative analgesic will be compared between the two groups using Student\u0026rsquo;s T-test or Mann\u0026ndash;Whitney U-test (after the normality test). Anesthesia-related complication will be analysed between the two groups using Chi-square test or Fisher\u0026rsquo;s exact test.\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWith the rapid development of the social economy and changes in people\u0026apos;s living lifestyles, the incidence of obesity is rapidly increasing. Obesity is often accompanied with metabolism related complications such as type 2 diabetes, hypertension, obstructive sleep apnea syndrome, arthritis and polycystic ovary, which is one of the important chronic diseases affecting people\u0026apos;s physical and mental health\u003csup\u003e27,28\u003c/sup\u003e.At present, the most effective treatment for obesity and related metabolic diseases is bariatric surgery. LSG is a highly valued surgical way from metabolic surgeons worldwide in recent years due to its simple procedure and good short-term efficacy\u003csup\u003e29\u003c/sup\u003e.In addition to reducing body weight, it also has therapeutic effect on obesity related metabolic diseases such as type 2 diabetes, hyperlipidemia, nonalcoholic fatty liver, etc\u003csup\u003e30\u003c/sup\u003e.The most important mission during the perioperative period of bariatric surgery is preventing the surgical complications. Postoperative discomfort mainly comes from pain, including gastrointestinal spasms and incision. Postoperative pain can produce long-lasting negative effects on the endocrine system, central nervous system, immune system, cardiovascular system, digestive system, etc. Thereby , translated into neuroendocrine signals, the result is an increased blood pressure, increased heart rate, increased gastric acid secretion, decreased immune function, emotional anxiety and depression. These consequences will all have an adverse effect on early exercise, delaying recovery, and even leading to the occurrence of complications.\u003c/p\u003e\n\u003cp\u003eCurrently, opioid drugs are the most widely used type of analgesic in clinic, due to their powerful analgesic effect and long duration. Except its positive effect, adverse reactions such as respiratory depression, nausea and vomiting, hyperalgesia, immune suppression and skin itching also occur as adverse complications\u003csup\u003e31\u003c/sup\u003e.Respiratory suppression is one of the most serious adverse reactions, especially to those with severe obesity and obstructive sleep apnea hypopnea syndrome\u003csup\u003e32\u003c/sup\u003e.In addition, bariatric surgery has a high incidence of postoperative nausea and vomiting in obese patients, opioid drugs can directly act on receptors in the brainstem chemical trigger area, exacerbating the occurrence of perioperative nausea and vomiting ,seriously affecting patient recovery\u003csup\u003e33\u003c/sup\u003e. Therefore, under the premise of effective pain relief, it\u0026rsquo;s important to integrate multiple non-opioid drugs and technologies to minimize the use of opioid drugs and their adverse effects in obese patients\u003csup\u003e34\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe safety and feasibility of OFA have been validated in various surgeries such as gynecological surgery\u003csup\u003e35\u003c/sup\u003e, thoracic surgery\u003csup\u003e36\u003c/sup\u003e etc. Based on the clinical characteristics of LSG, this trial developed\u0026nbsp;OFA via\u0026nbsp;using TAP combined with esketamine and dexmedetomidine to reduce postoperative pain, nausea and vomiting, and other complications, promoting postoperative recovery and reducing the incidence and severity of chronic pain. The drug doses selected in our study were all within the safe range according to our preliminary experiments, which has confirmed the effectiveness of the drug doses.\u003c/p\u003e\n\u003cp\u003eThe OFA study is a prospective double-blind, randomized controlled clinical trial evaluating the impact of OFA on severe postoperative opioid related adverse events. The OFA scheme for LSG may have the following advantages in accelerating postoperative rehabilitation:\u003c/p\u003e\n\u003cp\u003e1. The incidence of adverse reactions related to opioid drugs, such as hypoxemia and PONV, will be significantly reduced, ensuring the safety and comfort of patients.\u003c/p\u003e\n\u003cp\u003e2.\u0026nbsp;The valid perioperative analgesic effect of TAP, combined with the improvement effect of postoperative cognitive function of esketamine and dexmedetomidine can prevent postoperative\u0026nbsp;neurocognitive disorder. Meanwhile, it has the potential to reduce chronic pain, promote rapid recovery. However, there are currently no relevant research reports.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAlthough the feasibility of OFA has been validated in different types surgeries, its clinical application is still controversial, and there are currently many advocates for the application of OFA only in small and medium-sized surgeries.The limitations of this study are as follows：\u003c/p\u003e\n\u003cp\u003e1.These questionnaire are mostly obtained through patients own description, so the results tend to be biased towards subjective ratings of pain impressions by patients. Therefore, they may not directly measure the analgesic effect, leading to subjective bias. Therefore, before the start of this experiment, the visiting personnel received systematic training on the use of these questionnaires to avoid subjective bias as much as possible. Of course, the analysis indicators also include objective indicators such as the time to first out-of-bed mobilization, and the total amount of\u0026nbsp;analgesic needed.\u003c/p\u003e\n\u003cp\u003e2.This experiment is a small sample, single center study, and there is possible individual heterogeneity in obese patients. In the future, prospective trials with multiple centers and large samples are still expected to verify.\u003c/p\u003e\n\u003cp\u003eOverall, for obese patients, OFA seems to be superior to conventional schemes using opioid drugs , which can accelerate postoperative recovery and improve patient satisfaction. If OFA achieves positive results in this experiment, it will bring support for the promotion of OFA. OFA can not only reduce adverse reactions such as respiratory suppression, but also shorten hospitalization time, reduce medical costs, and save medical resources. However ,OFA is not without challenges,it is unclear whether OFA is beneficial and can improve the long-term prognosis of patients, and further research is needed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial status\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is protocol version 1.4 refined on 2024.01.25. This trial has been approved on 8 February 2024 by the Institutional Review Board of Beijing Friendship Hospital of Capital Medical University (2024-P2-004-02). Written informed consent will be obtained from all study participants.The trial started recruiting patients in March 2024 after registered on the clinicaltrials.gov(NCT06305221),and the recruiting period will last 12 months，ending in March 2025 approximately.\u0026nbsp;\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eERAS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003eenhanced recovery after surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eOFA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003eopioid-free analgesia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eLSG\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003elaparoscopic sleeve surgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eNMDA\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003eN-methyl-D-aspartate\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eQoR-15 \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003e15-item recovery quality scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eLRYGB \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003eLaparoscopic gastric bypass\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003ePONV\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003epostoperative nausea and vomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eASA \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003eAmerican Society of Anesthesiologists\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eBMI\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003ebody mass index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eOBA \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003eopioid anesthesia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eTAP\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003etransversus abdominis plane\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003ePACU \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003epost-anesthesia care unit\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eNRS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003eNumeric Rating Scale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003ePCIA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003epatient-controlled intravenous analgesia\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eOBAS\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003eoverall benefit of satisfaction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eCRF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003ecase report forms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 14.2606%;\"\u003e\n \u003cp\u003eDMC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 85.7394%;\"\u003e\n \u003cp\u003eData Monitoring Committee\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthical approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur research is conducted in accordance with the principles of the Declaration of Helsinki. Prior to starting, ethical approval have been obtained for all protocols from the clinicaltrials.gov. This trial has been approved by the Institutional Review Board of Beijing Friendship Hospital of Capital Medical University (2024-P2-004-02) on 8 February 2024. Written informed consent will be obtained from all study participants.\u003c/p\u003e\n\u003cp\u003eIn the process of this trial ,if we make some important modifications,such as changes to eligibility criteria, outcomes, analyses ,sample sizes,study procedures,etc,we\u0026nbsp;will apply for approval to the local medical ethical committee.Meanwhile ,all study participants will be notified, informed consent will be requested\u0026nbsp;again when necessary. And online trail registries in ClinicalTrials.gov will be updated.\u0026nbsp;The results of this research will be published in international journals.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable \u0026mdash; no identifying images、videos and other personal details relating to participants included in this trial .\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used, information materials of the participants during the experiment and informed consent forms are available from the corresponding author on reasonable request. ( Lei Wan, Email [email protected])\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors report no conflicts of interest in this work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors\u0026apos;.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWL is responsible for supervising the clinical study .TJQ and SBJ conceived the idea and designed this trial. TJQ and HHJ are responsible for the recruitment and treatment of participants. SBJ is responsible for the statistical analysis. This manuscript was drafted by TJQ and revised by WL. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eI would like to express my heartfelt thanks to all staff in the general surgical department of Beijing Friendship Hospital, Capital Medical University. All authors will acknowledge all the participants in this study.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBatchelder AJ, Williams R, Sutton C. et a1.Tlle evolution of minimally invasive bariatric surgery[J]. J Surg Res. 2013;183(2):559\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWang Y, Wang L. Qu W.New national data show alarming increase in obesity and noncommunicable chronic diseases in China[J]. Eur J Clin Nutr. 2017;71(1):149\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePonce J, DeMaria EJ, Nguyen NT. et a1.American Society for Metabolic and Bariatric Surgery estimation of bariatric surgery procedures in 201 5 and surgeon workforce in the United States[J]. Surg Obes Relat Dis. 2016;12(9):1637\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eChristou NV, Sampalis JS, Liberman M. et a1.Surgery decreases long\u0026mdash;term mortality,morbidity,and health care use in morbidly obese patients[J]. Ann Surg. 2004;240(3):416\u0026ndash;discussion423423.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAngrisani L, Santonicola A, Iovino P. et a1.Reply to LeRer to the Editor: Bariatric Surgery Worldwide 20 1 3 Reveals a Rise in Mini\u0026mdash;Gastric. Bypass[J] Obes Surg. 2015;25(1 1):2166\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAngrisani L, Santonicola A, Iovino P, et al. Bariatric Surgery Worldwide 2013[J]. Obes Surg. 2015;25(10):1822\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKhorgami Z, Shoar S, Andalib A, et al. Trends in utilization of bariatric surgery, 2010\u0026ndash;2014: sleeve gastrectomy dominates[J]. Surg Obes Relat Dis. 2017;13(5):774\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRosenthal RJ, Diaz AA, Arvidsson D, et al. International Sleeve Gastrectomy Expert Panel Consensus Statement: best practice guidelines based on experience of \u0026gt;\u0026thinsp;12, 000 cases[J]. Surg Obes Relat Dis. 2012;8(1):8\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFrezza EE, Reddy S, Gee LL, et al. Complications after sleeve gastrectomy for morbid obesity[J]. ObesSurg. 2009;19(6):684\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGan TJ, Diemunsch P, Habib AS, et al. Consensus guidelines for the management of postoperative nausea and vomiting[J]. Anesth Analg. 2014;118(1):85\u0026ndash;113.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBataille A, Letourneulx JF, Charmeau A, et al. Impact of a prophylactic combination of dexamethasone-ondansetron on postoperative nausea and vomiting in obese adult patients undergoing laparoscopic sleeve gastrectomy during closed-loop propofol-remifentanil anaesthesia: a randomised double-blind placebo-controlled study[J]. Eur J Anaesthesiol. 2016;33(12):898\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBeloeil H, Laviolle B, Menard C, et al. POFA trial study protocol: a multicentre, double-blind, randomised, controlled clinical trial comparing opioid-free versus opioid anaesthesia on postoperative opioid-related adverse events after major or intermediate non-cardiac surgery [J]. BMJ Open. 2018;8(6):e020873.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLee LA, Caplan RA, Stephens LS, et al. Postoperative opioid-induced respiratory depression: a closed claims analysis [J]. Anesthesiology. 2015;122(3):659\u0026ndash;65.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHollander SW, Sifft A, Hess S. et a1.Identifying the Bariatric Patient at Risk for Pulmonary Embolism: Prospective Clinical Using Duplex Sonography and Blood Screening[J].Obes Surg, 2015, 25(11):2011\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLavand'Homme P, Steyaert A. Opioid-free anesthesia opioid side effects: Tolerance and hyperalgesia [J]. Best Pract Res Clin Anaesthesiol. 2017;31(4):487\u0026ndash;98.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWeinbroum AA. Postoperative hyperalgesia-A clinically applicable narrative review [J]. Pharmacol Res. 2017;120:188\u0026ndash;205.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBaboli KM, Liu H, Poggio JL. Opioid-free postoperative analgesia: Is it feasible? [J]. Curr Probl Surg. 2020;57(7):100794.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eWei W, ZhangA, Liu L, et al. Effects of subanaesthetic S-ketamine on postoperative delirium and cognitive function in elderly patients undergoing non-cardiac thoracic surgery: a protocol for a randomised, double-blinded, placebo-controlled and positive-controlled, non-inferiority trial (SKED trial) [J]. BMJ Open. 2022;12(8):e061535.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLarue A, Jacquet-Lagreze M, Ruste M, et al. Opioid-free anaesthesia for video-assisted thoracoscopic surgery: A retrospective cohort study with propensity score analysis [J]. Anaesth Crit Care Pain Med. 2022;41(4):101089.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSelim J, Jarlier X, Clawier T, et al. Impact of Opioid-free Anesthesia After Video-assisted Thoracic Surgery: A Propensity Score Study [J]. Ann Thorac Surg. 2022;114(1):218\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAn G, Zhang Y, Chen N, et al. Opioid-free anesthesia compared to opioid anesthesia for lung cancer patients undergoing video-assisted thoracoscopic surgery: A randomized controlled study [J]. PLoS ONE. 2021;16(9):e0257279.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eStark PA, Myles PS, Berke JA. Development and psychometric evaluation of a postoperative quality of recovery score: the QoR-15 [J]. Anesthesiology. 2013;118(6):1332\u0026ndash;40.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLehmann N, Joshi GP, Dirkmann D, et al. Development and longitudinal validation of the overall benefit of analgesia score: a simple multi-dimensional quality assessment instrument. Br J Anaesth. 2010;105(4):511\u0026ndash;8. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/bja/aeq186\u003c/span\u003e\u003cspan address=\"10.1093/bja/aeq186\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKushner BS, Freeman D, Sparkman J, Salles A, Eagon JC, Eckhouse SR. Assessment of postoperative nausea and vomiting after bariatric surgery using a validated questionnaire. Surg Obes Relat Dis. 2020;16(10):1505\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLehmann N, Joshi GP, Dirkmann D, et al. Development and longitudinal validation of the overall benefit of analgesia score: a simple multi-dimensional quality assessment instrument [J]. Br J Anaesth. 2010;105(4):511\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eMyles PS, Myles DB. An Updated Minimal Clinically Important Difference for the QoR-15 Scale. Anesthesiology. 2021;135(5):934\u0026ndash;5. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/ALN.0000000000003977\u003c/span\u003e\u003cspan address=\"10.1097/ALN.0000000000003977\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSeeberg KA, Borgeraas H, Hoffo D, et al. Gastric By⁃ pass Versus Sleeve Gastrectomy in Type 2 Diabetes:Effects on Hepatic Steatosis and Fibrosis:A Randomized Controlled Trial [J]. Ann Intern Med. 2022;175(1):74\u0026ndash;83.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAminian A, Wilson R, Al⁃Kurd A, et al. Association of Bariatric Surgery With Cancer Risk and Mortality in Adults With Obesity[J]. JAMA. 2022;327(24):2423\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFouse T, BrethauerS. Resolution of comorbidities and impact on longevity following bariatric and metabolic surgery [J]. Sury Clin North Am. 2016;96:717\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePories WJ, Swanson MS, MacDonald KG, et al. Who would have thought it?an operation proves to be the most effective therapy for adult\u0026mdash;onset diabetes mellitus[J]. Ann Surg. 1995;222:339\u0026ndash;50.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKoepke EJ, Manning EL, Miller TE et al. The rising tide of opioid use and abuse:The role of the anesthesiologist[ J]. Perioper Med (Lond),2018,7:16.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTrotta M, Ferrari C, D'Alessandro G, et al. Enhanced recovery after bariatric surgery (ERABS) in a high-volume bariatric center[J].SurgObes. Relat Dis. 2019;15:1785\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAndrews PLR. Physiology of nausea and vomiting[J]. Br J Anesth. 1992;69(7 Suppl 1):S2\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eIbrahim M, Elnabtity AM, Hegab A, et al. Combined opioid free and loco-regional anaesthesia enhances the quality of recovery in sleeve gastrectomy done under ERAS protocol: a randomized controlled trial [J]. BMC Anesthesiol. 2022;22(1):29. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12871-021-01561-w\u003c/span\u003e\u003cspan address=\"10.1186/s12871-021-01561-w\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eZheng Z, Cheng W, Li L et al. Effect of opioid-free anesthesia on postoperative nausea and vomiting after gynecological surgery: a systematic review and meta-analysis.[J].Frontiers in pharmacology,2023,14:1330250.\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fphar.2023.1330250\u003c/span\u003e\u003cspan address=\"10.3389/fphar.2023.1330250\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eBello M, Oger S, Bedon -Carte S, et al. Effect of opioid -free anaesthesia on postoperative epidural ropivacaine requirement after thoracic surgery:a retrospective un- matched case -control study[J]. Anaesth Crit Care Pain Med. 2019;38(5):499\u0026ndash;505.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"opioid-free anesthesia, laparoscopic surgery, postoperative recovery, postoperative nausea and vomiting","lastPublishedDoi":"10.21203/rs.3.rs-5476305/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5476305/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e: Anesthesia for obese patient and postoperative pain management remains a big challenge. Their greater demand for opioids comes with both acute and long-term adverse effects，is calling for opioid-free anaesthetic strategies. Opioid-free anesthesia(OFA) is a multimodal anesthesia associating hypnotics, N-methyl-D-aspartate antagonists, local anesthetics, anti-inflammatory drugs and α-2 agonists to realize enhanced recovery after surgery(ERAS). With further research, we have confirmed that OFA is safe and feasible for laparoscopic surgery. However，how to select and combine the application of alternative drugs, need to be carefully selected. Therefore, the formulation of OFA programs and strategies plays a crucial role in ensuring effective suppression of surgical stress and reducing potential adverse reactions and complications of multi-drug combination.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: This prospective double-blind, randomized ,controlled clinical trial \u0026nbsp;will incorporate 76 patients scheduled for laparoscopic sleeve gastrectomy(LGS) surgery. The eligible population will be 1:1 randomly assigned to OFA or conventional anesthesia group. Primary endpoint was the 15-item recovery quality scale score after surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e: This trial explores the efficacy of opioid-free anesthesia in obesity patients, it provides more superior scheme than conventional one,which using opioid drugs . If OFA achieves positive results in this experiment, it will bring support for the promotion of OFA.It’s not only accelerate postoperative recovery ,but also improve patient satisfaction.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTrial Registration\u003c/strong\u003e: This trial registered at clinical trials.gov (NCT06305221) on 12 March 2024 (https://register.clinicaltrials.gov/prs/app/action/SelectProtocol).\u003c/p\u003e","manuscriptTitle":"Effect of Opioid-free Analgesia and Anesthesia on the Quality of Postoperative Recovery and Nausea Vomit in Obese Patients Receiving Laparoscopic Sleeve Gastrectomy: a study protocol for a prospective randomized controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-22 08:25:41","doi":"10.21203/rs.3.rs-5476305/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7c8910ad-d974-4b5b-8c7e-978a5cb144a9","owner":[],"postedDate":"July 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-10-09T02:46:24+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-22 08:25:41","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5476305","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5476305","identity":"rs-5476305","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}