Exploration of the effects of fospropofol disodium in anesthesia induction for elderly hip surgery: A study protocol for a Clinical Trial

Exploration of the effects of fospropofol disodium in anesthesia induction for elderly hip surgery: A study protocol for a Clinical 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 Exploration of the effects of fospropofol disodium in anesthesia induction for elderly hip surgery: A study protocol for a Clinical Trial Wenli Liao, Yuehong Wu, Lan Qiu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7053501/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. Fospropofol disodium is a novel water-soluble prodrug of propofol. This randomized controlled trial aimed to compare the efficacy and safety of fospropofol disodium versus etomidate for anesthesia induction in elderly patients undergoing hip surgery. Methods and analysis. This single-center, randomized, double-blind, controlled trial. It will enroll 120 elderly patients scheduled for hip surgery. Participants will be randomized in a 1:1 ratio to either the fospropofol disodium group (Group P) or the etomidate group (Group E). All patients will receive intravenous anesthesia induction with either fospropofol disodium or etomidate, according to their randomized group assignment. We will collect the following data，including: the time to loss of consciousness；the success rate of anesthesia induction; the incidence of injection pain, myoclonus, and sensory abnormalities within 30 seconds after initial dose administration; intraoperative hemodynamic stability; total intraoperative consumption of opioids, propofol, and vasoactive drugs; postoperative recovery time; the incidence of postoperative nausea and vomiting within 48 hours postoperatively; the incidence of postoperative delirium within 48 hours postoperatively; and serum high-sensitivity troponin T (hs-TnT) levels within 48 hours postoperatively. Data will be analyzed on an intention-to-treat basis and Per Protocol Analysis. Discussion We hypothesized that: fospropofol disodium would be clinically effective for anesthesia induction in elderly hip surgery patients; its hemodynamic stability would be non-inferior to etomidate; and it would demonstrate a superior safety profile with fewer adverse effects compared to etomidate. Clinical trial registration : The UK’s Clinical Study Registry ( ISRCTN registry ) https://www.isrctn.com/ISRCTN12170320 registration number: ISRCTN12170320 Date:01/07/2025 fospropofol disodium induction of anaesthesia elderly hip surgery Figures Figure 1 Figure 2 Introdution Hip disorders are prevalent among elderly populations and significantly impact quality of life, including hip osteoarthritis, hip fracture, proximal femoral fractures, and osteonecrosis of the femoral head. Geriatric hip fracture refers to fractures of the femoral neck and intertrochanteric region occurring in adults aged 65 years or older. With the progressive aging of the population, the number of geriatric hip fracture patients will continue to rise significantly. The treatment modalities for this condition include both conservative management and surgical intervention. Conservative treatment has a slow healing process and a high risk of complications, making it suitable only for patients who cannot or refuse to undergo surgical intervention. Current clinical consensus maintains that patients meeting surgical criteria should receive prompt operative intervention. The American Academy of Orthopaedic Surgeons clinical practice guidelines specifically recommend surgical treatment within 48 hours of diagnosis for eligible patients [ 1 ]. The review article 'Perioperative Blood Pressure Management' indicates that surgical patients with the following characteristics are more prone to hemodynamic instability during anesthesia induction: (1) ASA class III-V, (2) baseline MAP < 70 mmHg, (3) age ≥ 65 years, (4) propofol-based induction, and (5) increased fentanyl induction doses [ 2 ]. Therefore, to avoid severe hypotension, alternative agents to propofol should be considered for anesthesia induction in patients aged 65 years or older. Compared to propofol, etomidate demonstrates superior hemodynamic stability during anesthesia induction[ 3 ]. Etomidate is characterized by rapid onset and clearance. Due to its favorable profile of minimal cardiovascular/cerebral effects and relatively mild respiratory depression, it is widely used for: anesthesia induction, anesthesia maintenance, and rapid sequence intubation in critically ill patients[ 4 ]. However, the etomidate formulation most commonly used clinically is a lipid emulsion, which remains associated with injection pain and postoperative nausea/vomiting. Intravenous etomidate administration induces significant myoclonus and causes dose-dependent suppression of both corticosteroid and mineralocorticoid production, which clinically limits its utility to varying degrees[ 5 , 6 ]. Fospropofol disodium, administered intravenously, represents both a Category 1 sedative-hypnotic agent and the first water-soluble prodrug of propofol developed in China. Fospropofol disodium is associated with a low incidence of respiratory and circulatory adverse events, while offering a high success rate of sedation and prolonged duration of action. Additionally, it features a low occurrence of injection pain and myoclonus, with no lipid metabolism-related adverse effects [ 7 ]. It is now approved for the induction of general anesthesia in adults. However, there is limited clinical experience with fospropofol disodium in elderly patients aged 65 and older. Given its favorable efficacy and safety profile, we anticipate that it may prove beneficial for elderly patients undergoing hip surgery. Methods 2.1 Ethics and registration This study was approved by the Ethics Committee of the First People's Hospital of Changzhou. The trial was registered at a clinical trial registry prior to enrollment of the first participant (registration number: ISRCTN12170320). The study will be in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice Guidelines. The protocol follows the guidelines of Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) 2.2 Study design and status This study is a prospective, single-center, double-blind, randomized, controlled trial. It will be conducted in Changzhou First People's Hospital. At the time of submission, the first patient had not yet been recruited. The study’s enrollment period is anticipated to run from August 2025 to February 2026 (6 months). The anticipated study period is from April 16, 2025 to June 16, 2026.The version date of this study protocol is June 28, 2025, Version 1.0. Figure 1 shows the study flowchart. 2.3 Participants and enrollment Patients will be recruited from the adult surgical patient group undergoing hip surgery at The First People's Hospital of Changzhou. Eligibility criteria will be determined during the preoperative visit. The investigator or an authorised representative will explain the benefits and risks of participating in the trial to each patient, their legal guardian, or a notary witness, and written informed consent must be obtained before the patient enters the trial. The original informed consent form, signed and dated by the subject or their legal guardian and the person conducting the informed consent process, should be retained by the investigator. We set the following inclusion and exclusion criteria for this trial: inclusion criteria: elderly patients aged 65–74 years; BMI 18–27 kg/m2; ASA physical status classification I-III; Scheduled for hip surgery requiring general anesthesia with endotracheal intubation. Exclusion criteria: refusal of general anaesthesia; known allergy to general anaesthetics; preoperative cognitive dysfunction; significant hepatic and renal function dysfunction; baseline blood pressure ≥ 180/110 mmHg or ≤ 90/60 mmHg; clinically significant cardiovascular, cerebrovascular, or respiratory diseases; bilateral joint surgery; revision arthroplasty; multiple trauma injuries; history of general or regional anesthesia within 3 months. Exclusion criteria: protocol violations regarding concomitant medications affecting outcomes; incomplete data compromising efficacy/safety evaluation. Withdrawal criteria: cases withdrawn for reasons other than adverse events or lack of efficacy; patients requesting treatment regimen changes. Termination criteria: Investigator-determined medical necessity for discontinuation; patient-initiated withdrawal request. 2.4 Randomization and blinding This study employed a double-blind design. An independent clinical coordinator (not involved in subsequent research procedures) used SPSS 26.0 software to randomly allocate 120 participants in a 1:1 ratio to either the fospropofol disodium group (Group P) or the etomidate group (Group E). The allocation information was sealed in opaque, sequentially numbered envelopes. Prior to anesthesia induction, the attending anesthesiologist opened the sealed envelope to reveal group allocation and proceeded according to the assigned treatment arm. Postoperatively, data collection was performed by an anesthesiologist blinded to group allocation. All surgical procedures were completed by the same surgical team. Throughout the study period, both patients and outcome-assessing anesthesiologists remained unaware of treatment assignments. schedule of enrolment, interventions, and assessments Schedule of enrolment, interventions, and assessments were in accordance with the SPIRIT statement (Fig. 2) Figure2 schedule of enrolment, interventions, and assessments According to SPIRIT, 2013 statement of defining standard protocol items for clinical trials[ 8 ] 2.5 Study intervention Group P received intravenous anesthesia induction with fospropofol disodium at the minimum effective induction dose of 10 mg/kg, administered as a constant-rate intravenous injection over 60 seconds. Group E received intravenous anesthesia induction with etomidate at a dose of 0.3 mg/kg, administered as a constant-rate intravenous injection over 60 seconds 2.6 Perioperative management Upon entering the operating room, standard monitoring was established, including electrocardiogram (ECG), non-invasive blood pressure (NIBP), heart rate (HR), pulse oximetry (SpO₂), and bispectral index (BIS). Peripheral intravenous access was obtained in the upper extremity. Twenty minutes before surgury, all subjects received ultrasound-guided ipsilateral fascia iliaca compartment block with 0.25% ropivacaine (0.6 mL/kg, total dose not exceeding 100 mg). Both groups received pre-induction fluid loading (5 mL/kg over 20 minutes) along with intravenous parecoxib sodium 50 mg and sufentanil 0.1 µg/kg prior to anesthesia induction. Induction was then initiated in both groups with intravenous anesthetics (fospropofol disodium for Group P, etomidate for Group E). The time from completion of injection to loss of consciousness (LoC) was recorded. LoC was defined as loss of eyelash reflex and unresponsiveness to verbal command after two attempts. If the patient failed to achieve LoC within 20 minutes of injection, general anesthesia induction was considered a failure. After confirmation of loss of consciousness (LOC), patients received sequential intravenous administration of sufentanil 0.30 µg/kg followed by cisatracurium besylate 0.15 mg/kg. After 3 minutes of preoxygenation with mask ventilation, perform tracheal intubation under video laryngoscopy, followed by mechanical ventilation. If the patient's systolic blood pressure and heart rate do not decrease by at least 20% from baseline before tracheal intubation, it is considered a hazardous stress response during intubation, and 1 µg/kg of remifentanil should be administered intravenously. Record the time from completion of sedative administration until the BIS value reaches 60. When the patient's BIS reaches 60, administer an additional 1 mg/kg of propofol and initiate a continuous infusion of propofol and remifentanil to maintain anesthesia. Adjust the dosage based on vital signs, and maintain the intraoperative BIS value between 45 and 65. During skin closure at the end of the surgery, perform subcutaneous infiltration anesthesia with 20ml of 0.375% ropivacaine combined with intravenous administration of 0.1 µg/kg sufentanil. The propofol and remifentanil infusions were discontinued upon surgical completion. All patients underwent tracheal extubation in the PACU (Post-Anesthesia Care Unit) and were maintained under monitoring until achieving a modified Aldrete score of ≥ 9, at which point discharge was permitted. 2.7 Data collection. During the pre-anesthesia evaluation conducted one day prior to surgery, patient demographic data [including age, sex, height, weight, and body mass index (BMI)] and baseline characteristics were collected. These included: comorbidities (hypertension, coronary artery disease, diabetes mellitus, and others), preoperative medications (names, dosages, and administration schedules), baseline MAP and HR values, ASA physical status, surgical history, allergy history, as well as laboratory tests or imaging studies when available.The data collection was performed by an anesthesiologist blinded to the group allocation. All raw data were recorded in case report forms, which were subsequently submitted to the statistician for analysis upon trial completion. 2.8 Study Outcomes 2.8.1 Primary outcome : Time to reach loss of consciousness (LoC) 2.8.2Secondary outcomes :1) Success rate of anaesthesia induction;2) Hemodynamic stability: Systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) measured at: before anesthesia induction, at time of LoC achievement, immediately after tracheal intubation, at surgical incision, 20 minutes post-incision;3)Incidence of injection pain, myoclonus, and paresthesia within 30s of initial dose injection;4) Total intraoperative consumption of sufentanil, remifentanil, propofol, and vasoactive agents;5)Postoperative recovery time, defined as the time from the end of surgery to the removal of the endotracheal tube;6) The incidence of nausea and vomiting during recovery period, at 24 and 48 hours of postoperative follow-up;7)Incidence of postoperative delirium (POD), during recovery period, at 24 and 48 hours of postoperative follow-up, as evaluated by the Confusion Assessment Method ;8)Serum hs-TnT levels: hs-TnT levels were monitored preoperatively (at least 2 hours preoperatively) and 2 days postoperatively (every morning). 2.9 Pre-assessment of Potential Risks and Corresponding Management Protocols Before induction of anaesthesia: All patients received intravenous palonosetron hydrochloride (10 mg) and dexamethasone (5 mg) to prevent postoperative nausea and vomiting (PONV); both groups underwent anaesthesia to expand the volume of rapid rehydration 5ml/kg to reduce the incidence of severe hypotension. Anesthesia Induction and intraoperative: Continuous Bispectral Index (BIS) monitoring was employed throughout the procedure to prevent inadequate sedation or intraoperative awareness ,if BIS values exceeded 65 at any time, an additional bolus of propofol (0.5–1 mg/kg IV) was administered; If systolic blood pressure (SBP) increased by ≥ 20% from baseline, the following actions were taken based on the Surgical Pleth Index (SPI), If SPI was between 20–50, 0.5 mg/kg uradil was injected intravenously; if SPI ≥ 50, 0.1ug/kg sufentanil was added; If the patient's systolic blood pressure (SBP) decreases by more than 20% from baseline and persists for 5 minutes, administer phenylephrine 40–80 µg intravenously; If the patient's heart rate (HR) is ≤ 50 bpm, administer atropine 0.5 mg intravenously; if HR is ≥ 100 bpm, administer esmolol 20–30 mg intravenously; Monitor intraoperative blood loss and administer blood transfusion when clinically indicated; Intraoperative and postoperative: all patients received multimodal analgesia, including nonsteroidal anti-inflammatory drug hyperalgesia, nerve block and subcutaneous infiltration anaesthesia to prevent inadequate analgesia. Adverse events defined as all adverse medical events occurring in subjects after receiving the investigational drug, which may manifest as symptoms, signs, diseases, or abnormal laboratory test results, but may not necessarily have a causal relationship with the investigational drug. All adverse events occurring in subjects during the trial, including abnormal laboratory test results, must be thoroughly investigated and followed up. All adverse events must be assessed for their nature, severity, and relationship to the drug, and strictly recorded in the case report form. The relationship between adverse events and the investigational drug is categorised as: definitely related, probably related, possibly related, possibly unrelated, or definitely unrelated. The incidence rate of adverse reactions is calculated using the categories ‘definitely related,’ ‘probably related,’ and ‘possibly related.’ The severity or intensity of adverse events is classified into three levels: mild, moderate, and severe. In the event of a serious adverse reaction, it must be reported to the reporting unit within 24 hours, and the serious adverse event form must be completed. 2.10 Sample size calculation According to previous literature, the anticipated time to loss of consciousness (LOC) was estimated to be 62.96 ± 13.32 s in Group P and 55.8 ± 6.74 seconds in Group E [ 9 ]. The level of significance (α) was set at 0.05 (two-sided test) and statistical efficacy (1-β) at 90%. Sample size calculation was performed using PASS 2023 software. The results indicated a minimum requirement of 48 subjects per group. Accounting for a potential 20% dropout rate, we ultimately enrolled 120 participants in each group. 2.11 Statistical analysis Statistical analysis was performed using SPSS 26.0 software. Continuous variables such as time to loss of consciousness, hemodynamic parameters, drug dosage, postoperative recovery time, and serum hs-TnT levels were described using mean ± standard deviation or median (interquartile range) based on whether they followed a normal distribution, and categorical variables such as successful induction of anesthesia and occurrence of adverse reactions were described using frequencies and percentages. T First, a baseline analysis was performed on the demographic characteristics of the enrolled cases in both groups to assess their balance and comparability. Subsequently, the efficacy and safety outcomes were compared between the two groups. For continuous variables between the experimental and control groups, comparisons were made using the independent samples t-test or Mann-Whitney U test, as appropriate. Categorical variables were compared using the chi-square (χ²) test or Fisher's exact test. All statistical tests were two-sided, and a p-value ≤ 0.05 was considered statistically significant. Discussion Given the ongoing global population aging, the number of individuals aged ≥ 60 years is expected to hit 2.1 billion by mid-century (2050) [ 10 ]. The combination of osteoporosis, sarcopenia, and postural instability creates a high-risk triad for fragility fractures in aging populations. The number of hip fracture cases worldwide is projected to reach 4.5 million by 2050 [ 11 ]. Hip fractures are a leading cause of disability and are associated with high mortality rates, with one-year mortality reaching up to 30%[ 12 ]. A hip fracture usually causes sharp pain in the front of the groin (sometimes spreading to the thigh or buttock), making standing impossible. The injured leg may appear turned outward or shorter. Radiographic confirmation is mandatory [ 13 ]. Surgery represents the first-line treatment for most cases [ 1 ]. However, due to the physiological decline in elderly patients and their increased likelihood of multiple comorbidities, selecting appropriate anesthesia management is crucial. General anesthesia combined with nerve blocks is currently the most widely used approach,but elderly patients exhibit increased sensitivity to anesthetic agents, elevating the risk of intraoperative adverse events such as hypotension and hypoxemia. Therefore, particular attention must be paid to the selection of sedative agents. Etomidate is a short-acting intravenous anesthetic agent. Beyond its advantages of rapid onset and quick recovery, etomidate demonstrates minimal cardiovascular impact, providing greater hemodynamic stability during induction and surgery while reducing the need for vasoactive drugs. These properties make it particularly suitable for anesthesia induction in elderly patients and those with cardiovascular compromise [ 14 ]. However, etomidate may induce myoclonic movements, with reported incidence rates of 50–80%. While these are typically transient and non-pathological, they may lead to severe consequences in specific patient populations (including those with full stomachs, malignant hypertension, aneurysms, or hyperkalemia). The precise therapeutic targets for prevention remain unclear [ 11 , 15 ]. Additionally, this medication may cause injection site pain and postoperative nausea and vomiting (PONV)[ 7 ] ,and meta-analyses demonstrate a significant association between etomidate induction and postoperative delirium (pooled OR 4.4)[ 16 ]. Morever, etomidate may additionally suppress 11β-hydroxylase activity, thereby interfering with adrenal corticosteroid synthesis. This pharmacological effect could potentially increase postoperative mortality risk in patients[ 17 ] . Fospropofol disodium (Lusedra), a sedative-hypnotic agent developed by Eisai Inc. (USA), received FDA approval in 2008 for inducing monitored anesthesia care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures. Fospropofol was primarily indicated for sedation during bronchoscopy and gastrointestinal endoscopy, as well as outpatient minor surgeries. However, its requirement for anesthesiologist administration and limited advantages in ambulatory surgical settings contributed to poor market performance, ultimately leading to its market withdrawal in 2012. The newly approved fospropofol disodium is a water-soluble prodrug of propofol independently developed in China. Although both drugs share the same primary chemical component disodium 2,6-diisopropylphenoxymethyl phosphate, disodium salt (C₁₃H₁₉O₅PNa₂) - they differ in excipients, dosage forms, and manufacturing processes, which necessitates careful differentiation. Fospropofol disodium (2,6diisopropylphenoxymethyl phosphate, disodium salt) is inactive until converted by the body's alkaline phosphatase enzymes into active propofol (2,6-diisopropylphenol). Propofol activates GABA receptors on the postsynaptic membrane of central neurons, increasing chloride ion influx and reducing the excitability of the postsynaptic membrane. Simultaneously, it inhibits NMDA receptor-mediated calcium ion influx, suppressing postsynaptic neurons and producing sedative-hypnotic effects. [ 18 ]. A previous Phase 1 clinical trial investigating the pharmacokinetics of fospropofol disodium injection in 10 healthy volunteers found that a single intravenous bolus dose of 10 mg/kg resulted in a maximum plasma concentration of propofol at 1.96 ± 0.47 mg/mL, achieved in 10.06 ± 2.63 minutes. The elimination half-life was 150.72 ± 42.63 minutes, demonstrating linear pharmacokinetic characteristics[ 19 ]. No severe adverse reactions were observed in either the Phase I or Phase II safety clinical trials of this drug [ 20 , 21 ]. Compared to induction with 2 mg/kg propofol, induction using 20 mg/kg fospropofol disodium resulted in a longer onset time and prolonged duration of anesthesia. In the fospropofol disodium group, the time to achieve an MOAA/S score of 1 and loss of eyelash reflex was 3.1 ± 0.7 min, while the recovery time was 37 ± 9 min [ 20 , 21 ], which suggests that fospropofol disodium may be suitable for anesthesia induction in patients who do not require rapid onset and are undergoing relatively prolonged surgical procedures. In a multicenter Phase III clinical study, fospropofol disodium injection demonstrated comparable anesthesia induction success rates to propofol, while reducing the risk of myocardial suppression and effectively avoiding injection pain[ 7 ]. Currently, there are relatively few prospective clinical trials on fospropofol disodium, and no studies have yet investigated its efficacy and safety compared to etomidate for anesthesia induction in elderly patients undergoing hip surgery.. The recommended induction dosage of fospropofol disodium for adults is 10–15 mg/kg according to current guidelines [ 22 ]. However, considering the lower plasma protein levels in elderly patients, which result in reduced bound drug concentrations and increased free drug concentrations, this study used the minimum induction dose of 10 mg/kg of fospropofol disodium for induction. First, this study was limited to elderly patients undergoing hip surgery, which may restrict the generalizability of the findings. Future research should expand to include other surgical populations (e.g., abdominal or cardiovascular surgeries) to validate the applicability of the results. Second, as a single-center study with a relatively small sample size (n = 120), the statistical power may be insufficient, potentially affecting the robustness of the conclusions. Therefore, further multicenter, large-scale randomized controlled trials are warranted to enhance the external validity and reliability of the findings Declarations Ethics approval and consent to participate This study was approved by the Ethics Committee of the First People's Hospital of Changzhou . Written, informed consent to participate will be obtained from all participants. Consent for publication Not applicable Availability of data and materials The data for this study are available from the corresponding author for valid reasons. Competing interests The authors declare that they have no competing interests Funding: This study was not funded Author Contributions. WLL was responsible for experimental design, figure preparation, and manuscript drafting; YHW was responsible for study conceptualization and manuscript editing; LQ supervised research quality and critically revised the manuscript. All authors discussed results and approved the final version. Acknowledgements: Not applicable References Roberts KC, Brox WT. AAOS Clinical Practice Guideline: Management of Hip Fractures in the Elderly. J Am Acad Orthop Surg. 2015;23(2):138-40. Saugel B, Sessler DI. Perioperative Blood Pressure Management. Anesthesiology. 2021;134(2):250-61. Song JC, Lu ZJ, Jiao YF, Yang B, Gao H, Zhang J, et al. Etomidate Anesthesia during ERCP Caused More Stable Haemodynamic Responses Compared with Propofol: A Randomized Clinical Trial. Int J Med Sci. 2015;12(7):559-65. Mullick P, Talwar V, Aggarwal S, Prakash S, Pawar M. Comparison of priming versus slow injection for reducing etomidate-induced myoclonus: a randomized controlled study. Korean J Anesthesiol. 2018;71(4):305-10. Sneyd JR, Valk BI. Etomidate and its derivatives: time to say goodbye? Br J Anaesth. 2025;134(1):11-3. Zhang H, Wu A, Nan X, Yang L, Zhang D, Zhang Z, et al. The Application and Pharmaceutical Development of Etomidate: Challenges and Strategies. Mol Pharm. 2024;21(12):5989-6006. Wu CM, Zhang WS, Liu J, Zhang WY, Ke BW. Efficacy and Safety of Fospropofol Disodium for Injection in General Anesthesia Induction for Adult Patients: A Phase 3 Trial. Front Pharmacol. 2021;12:687894. A-W C, JM T, PC G, DG A, H M, J B, et al. SPIRIT 2013 Explanation and Elaboration: Guidance for protocols of clinical trials. BMJ. 2013:346:e7586. Si Y, Feng J, Xia L. The efficacy of fospropofol disodium in general anesthesia induction for elderly ureteroscopic lithotripsy patients. HENAN JOUＲNAL OF SUＲGEＲY 2024. Cheung EYN, Tan KCB, Cheung CL, Kung AWC. Osteoporosis in East Asia: Current issues in assessment and management. Osteoporos Sarcopenia. 2016;2(3):118-33. Berry JM, Merin RG. Etomidate myoclonus and the open globe. Anesth Analg. 1989;69(2):256-9. Schroeder JD, Turner SP, Buck E. Hip Fractures: Diagnosis and Management. Am Fam Physician. 2022;106(6):675-83. LeBlanc KE, Muncie HL, Jr., LeBlanc LL. Hip fracture: diagnosis, treatment, and secondary prevention. Am Fam Physician. 2014;89(12):945-51. Xia Z, Kamra K, Dong J, Harp KA, Xiong Y, Lisco SJ, et al. Comparison of efficacy and safety of etomidate with other anesthesia induction drugs for patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized controlled trials. Heliyon. 2024;10(22):e38274. Feng Y, Cheng YX, Wang XH. Etomidate-Induced myoclonus in Sprague‒Dawley rats involves the activation of neocortical Calpain-2 and its decrement on KCC2 protein. BMC Anesthesiol. 2025;25(1):213. He M, Zhu Z, Jiang M, Liu X, Wu R, Zhou J, et al. Risk Factors for Postanesthetic Emergence Delirium in Adults: A Systematic Review and Meta-analysis. J Neurosurg Anesthesiol. 2024;36(3):190-200. Preziosi P, Vacca M. Adrenocortical suppression and other endocrine effects of etomidate. Life Sci. 1988;42(5):477-89. Marik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49. Y. YL, L. R, X. Y, P. XX, S. QG, Y K. The Pharmacokinetic Study of the Active Metabolite of HX0507 in Healthy Volunteer. West China J Pharm Sci. 2012:298–301. Yi XQ, Li R, Zhang WS, Liu J, Xu J, Liao TZ. [Effect of single doses of HX0507 on QTc intervals in healthy people: a phase I safety and tolerability study]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2012;43(6):868-72. Liu R, Luo C, Liu J, Zhang W, Li Y, Xu J. Efficacy and Safety of FospropofolFD Compared to Propofol When Given During the Induction of General Anaesthesia: A Phase II, Multi-centre, Randomized, Parallel-Group, Active-Controlled, Double-Blind, Double-Dummy Study. Basic Clin Pharmacol Toxicol. 2016;119(1):93-100. J L. Guidance on the clinical application of fospropofol disodium. Chinese J Anesthesio. 2023;43:912–5. 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1","display":"","copyAsset":false,"role":"figure","size":48208,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of the study\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7053501/v1/31386961903194ad9b0755cb.png"},{"id":94139565,"identity":"6468349a-f70f-43ff-a75a-065b39230395","added_by":"auto","created_at":"2025-10-22 19:34:10","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":261574,"visible":true,"origin":"","legend":"\u003cp\u003eschedule of enrolment, interventions, and assessments\u003c/p\u003e","description":"","filename":"21.png","url":"https://assets-eu.researchsquare.com/files/rs-7053501/v1/f6bd4c9d5a361f23929b4026.png"},{"id":99310401,"identity":"373a9a4a-accf-47d1-b785-6c3ea4a387cc","added_by":"auto","created_at":"2025-12-31 16:12:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":846472,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7053501/v1/ad0f469e-2384-44a4-ae7b-1f6cdfd59681.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eExploration of the effects of fospropofol disodium in anesthesia induction for elderly hip surgery: A study protocol for a Clinical Trial\u003c/p\u003e","fulltext":[{"header":"Introdution","content":"\u003cp\u003eHip disorders are prevalent among elderly populations and significantly impact quality of life, including hip osteoarthritis, hip fracture, proximal femoral fractures, and osteonecrosis of the femoral head. Geriatric hip fracture refers to fractures of the femoral neck and intertrochanteric region occurring in adults aged 65 years or older. With the progressive aging of the population, the number of geriatric hip fracture patients will continue to rise significantly. The treatment modalities for this condition include both conservative management and surgical intervention. Conservative treatment has a slow healing process and a high risk of complications, making it suitable only for patients who cannot or refuse to undergo surgical intervention. Current clinical consensus maintains that patients meeting surgical criteria should receive prompt operative intervention. The American Academy of Orthopaedic Surgeons clinical practice guidelines specifically recommend surgical treatment within 48 hours of diagnosis for eligible patients [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The review article 'Perioperative Blood Pressure Management' indicates that surgical patients with the following characteristics are more prone to hemodynamic instability during anesthesia induction: (1) ASA class III-V, (2) baseline MAP\u0026thinsp;\u0026lt;\u0026thinsp;70 mmHg, (3) age\u0026thinsp;\u0026ge;\u0026thinsp;65 years, (4) propofol-based induction, and (5) increased fentanyl induction doses [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Therefore, to avoid severe hypotension, alternative agents to propofol should be considered for anesthesia induction in patients aged 65 years or older. Compared to propofol, etomidate demonstrates superior hemodynamic stability during anesthesia induction[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eEtomidate is characterized by rapid onset and clearance. Due to its favorable profile of minimal cardiovascular/cerebral effects and relatively mild respiratory depression, it is widely used for: anesthesia induction, anesthesia maintenance, and rapid sequence intubation in critically ill patients[\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. However, the etomidate formulation most commonly used clinically is a lipid emulsion, which remains associated with injection pain and postoperative nausea/vomiting. Intravenous etomidate administration induces significant myoclonus and causes dose-dependent suppression of both corticosteroid and mineralocorticoid production, which clinically limits its utility to varying degrees[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFospropofol disodium, administered intravenously, represents both a Category 1 sedative-hypnotic agent and the first water-soluble prodrug of propofol developed in China. Fospropofol disodium is associated with a low incidence of respiratory and circulatory adverse events, while offering a high success rate of sedation and prolonged duration of action. Additionally, it features a low occurrence of injection pain and myoclonus, with no lipid metabolism-related adverse effects [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. It is now approved for the induction of general anesthesia in adults. However, there is limited clinical experience with fospropofol disodium in elderly patients aged 65 and older. Given its favorable efficacy and safety profile, we anticipate that it may prove beneficial for elderly patients undergoing hip surgery.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.1 Ethics and registration\u003c/h2\u003e\u003cp\u003e This study was approved by the Ethics Committee of the First People's Hospital of Changzhou. The trial was registered at a clinical trial registry prior to enrollment of the first participant (registration number: ISRCTN12170320). The study will be in accordance with the Declaration of Helsinki and the International Conference on Harmonisation Good Clinical Practice Guidelines. The protocol follows the guidelines of Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT)\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.2 Study design and status\u003c/h2\u003e\u003cp\u003eThis study is a prospective, single-center, double-blind, randomized, controlled trial. It will be conducted in Changzhou First People's Hospital. At the time of submission, the first patient had not yet been recruited. The study\u0026rsquo;s enrollment period is anticipated to run from August 2025 to February 2026 (6 months). The anticipated study period is from April 16, 2025 to June 16, 2026.The version date of this study protocol is June 28, 2025, Version 1.0. Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the study flowchart.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Participants and enrollment\u003c/h2\u003e\u003cp\u003ePatients will be recruited from the adult surgical patient group undergoing hip surgery at The First People's Hospital of Changzhou. Eligibility criteria will be determined during the preoperative visit. The investigator or an authorised representative will explain the benefits and risks of participating in the trial to each patient, their legal guardian, or a notary witness, and written informed consent must be obtained before the patient enters the trial. The original informed consent form, signed and dated by the subject or their legal guardian and the person conducting the informed consent process, should be retained by the investigator. We set the following inclusion and exclusion criteria for this trial: inclusion criteria: elderly patients aged 65\u0026ndash;74 years; BMI 18\u0026ndash;27 kg/m2; ASA physical status classification I-III; Scheduled for hip surgery requiring general anesthesia with endotracheal intubation. Exclusion criteria: refusal of general anaesthesia; known allergy to general anaesthetics; preoperative cognitive dysfunction; significant hepatic and renal function dysfunction; baseline blood pressure\u0026thinsp;\u0026ge;\u0026thinsp;180/110 mmHg or \u0026le;\u0026thinsp;90/60 mmHg; clinically significant cardiovascular, cerebrovascular, or respiratory diseases; bilateral joint surgery; revision arthroplasty; multiple trauma injuries; history of general or regional anesthesia within 3 months. Exclusion criteria: protocol violations regarding concomitant medications affecting outcomes; incomplete data compromising efficacy/safety evaluation. Withdrawal criteria: cases withdrawn for reasons other than adverse events or lack of efficacy; patients requesting treatment regimen changes. Termination criteria: Investigator-determined medical necessity for discontinuation; patient-initiated withdrawal request.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Randomization and blinding\u003c/h2\u003e\u003cp\u003eThis study employed a double-blind design. An independent clinical coordinator (not involved in subsequent research procedures) used SPSS 26.0 software to randomly allocate 120 participants in a 1:1 ratio to either the fospropofol disodium group (Group P) or the etomidate group (Group E). The allocation information was sealed in opaque, sequentially numbered envelopes. Prior to anesthesia induction, the attending anesthesiologist opened the sealed envelope to reveal group allocation and proceeded according to the assigned treatment arm. Postoperatively, data collection was performed by an anesthesiologist blinded to group allocation. All surgical procedures were completed by the same surgical team. Throughout the study period, both patients and outcome-assessing anesthesiologists remained unaware of treatment assignments. schedule of enrolment, interventions, and assessments Schedule of enrolment, interventions, and assessments were in accordance with the SPIRIT statement (Fig.\u0026nbsp;2)\u003c/p\u003e\u003cp\u003eFigure2 schedule of enrolment, interventions, and assessments\u003c/p\u003e\n\u003cp\u003eAccording to SPIRIT, 2013 statement of defining standard protocol items for clinical trials[\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e\n\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\n \u003ch2\u003e2.5 Study intervention\u003c/h2\u003e\n \u003cp\u003eGroup P received intravenous anesthesia induction with fospropofol disodium at the minimum effective induction dose of 10 mg/kg, administered as a constant-rate intravenous injection over 60 seconds. Group E received intravenous anesthesia induction with etomidate at a dose of 0.3 mg/kg, administered as a constant-rate intravenous injection over 60 seconds\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\n \u003ch2\u003e2.6 Perioperative management\u003c/h2\u003e\n \u003cp\u003eUpon entering the operating room, standard monitoring was established, including electrocardiogram (ECG), non-invasive blood pressure (NIBP), heart rate (HR), pulse oximetry (SpO₂), and bispectral index (BIS). Peripheral intravenous access was obtained in the upper extremity. Twenty minutes before surgury, all subjects received ultrasound-guided ipsilateral fascia iliaca compartment block with 0.25% ropivacaine (0.6 mL/kg, total dose not exceeding 100 mg). Both groups received pre-induction fluid loading (5 mL/kg over 20 minutes) along with intravenous parecoxib sodium 50 mg and sufentanil 0.1 \u0026micro;g/kg prior to anesthesia induction. Induction was then initiated in both groups with intravenous anesthetics (fospropofol disodium for Group P, etomidate for Group E). The time from completion of injection to loss of consciousness (LoC) was recorded. LoC was defined as loss of eyelash reflex and unresponsiveness to verbal command after two attempts. If the patient failed to achieve LoC within 20 minutes of injection, general anesthesia induction was considered a failure. After confirmation of loss of consciousness (LOC), patients received sequential intravenous administration of sufentanil 0.30 \u0026micro;g/kg followed by cisatracurium besylate 0.15 mg/kg. After 3 minutes of preoxygenation with mask ventilation, perform tracheal intubation under video laryngoscopy, followed by mechanical ventilation. If the patient\u0026apos;s systolic blood pressure and heart rate do not decrease by at least 20% from baseline before tracheal intubation, it is considered a hazardous stress response during intubation, and 1 \u0026micro;g/kg of remifentanil should be administered intravenously. Record the time from completion of sedative administration until the BIS value reaches 60. When the patient\u0026apos;s BIS reaches 60, administer an additional 1 mg/kg of propofol and initiate a continuous infusion of propofol and remifentanil to maintain anesthesia. Adjust the dosage based on vital signs, and maintain the intraoperative BIS value between 45 and 65. During skin closure at the end of the surgery, perform subcutaneous infiltration anesthesia with 20ml of 0.375% ropivacaine combined with intravenous administration of 0.1 \u0026micro;g/kg sufentanil. The propofol and remifentanil infusions were discontinued upon surgical completion. All patients underwent tracheal extubation in the PACU (Post-Anesthesia Care Unit) and were maintained under monitoring until achieving a modified Aldrete score of \u0026ge;\u0026thinsp;9, at which point discharge was permitted.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\n \u003ch2\u003e2.7 Data collection.\u003c/h2\u003e\n \u003cp\u003eDuring the pre-anesthesia evaluation conducted one day prior to surgery, patient demographic data [including age, sex, height, weight, and body mass index (BMI)] and baseline characteristics were collected. These included: comorbidities (hypertension, coronary artery disease, diabetes mellitus, and others), preoperative medications (names, dosages, and administration schedules), baseline MAP and HR values, ASA physical status, surgical history, allergy history, as well as laboratory tests or imaging studies when available.The data collection was performed by an anesthesiologist blinded to the group allocation. All raw data were recorded in case report forms, which were subsequently submitted to the statistician for analysis upon trial completion.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e\n \u003ch2\u003e2.8 Study Outcomes\u003c/h2\u003e\n \u003cdiv id=\"Sec11\" class=\"Section3\"\u003e\n \u003ch2\u003e\u003cstrong\u003e2.8.1 Primary outcome\u003c/strong\u003e: Time to reach loss of consciousness (LoC)\u003c/h2\u003e\n \u003cp\u003e\u003cstrong\u003e2.8.2Secondary outcomes\u003c/strong\u003e:1) Success rate of anaesthesia induction;2) Hemodynamic stability: Systolic blood pressure (SBP), mean arterial pressure (MAP), and heart rate (HR) measured at: before anesthesia induction, at time of LoC achievement, immediately after tracheal intubation, at surgical incision, 20 minutes post-incision;3)Incidence of injection pain, myoclonus, and paresthesia within 30s of initial dose injection;4) Total intraoperative consumption of sufentanil, remifentanil, propofol, and vasoactive agents;5)Postoperative recovery time, defined as the time from the end of surgery to the removal of the endotracheal tube;6) The incidence of nausea and vomiting during recovery period, at 24 and 48 hours of postoperative follow-up;7)Incidence of postoperative delirium (POD), during recovery period, at 24 and 48 hours of postoperative follow-up, as evaluated by the Confusion Assessment Method ;8)Serum hs-TnT levels: hs-TnT levels were monitored preoperatively (at least 2 hours preoperatively) and 2 days postoperatively (every morning).\u003c/p\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003e2.9 Pre-assessment of Potential Risks and Corresponding Management Protocols\u003c/h2\u003e\n \u003cp\u003eBefore induction of anaesthesia: All patients received intravenous palonosetron hydrochloride (10 mg) and dexamethasone (5 mg) to prevent postoperative nausea and vomiting (PONV); both groups underwent anaesthesia to expand the volume of rapid rehydration 5ml/kg to reduce the incidence of severe hypotension. Anesthesia Induction and intraoperative: Continuous Bispectral Index (BIS) monitoring was employed throughout the procedure to prevent inadequate sedation or intraoperative awareness ,if BIS values exceeded 65 at any time, an additional bolus of propofol (0.5\u0026ndash;1 mg/kg IV) was administered; If systolic blood pressure (SBP) increased by \u0026ge;\u0026thinsp;20% from baseline, the following actions were taken based on the Surgical Pleth Index (SPI), If SPI was between 20\u0026ndash;50, 0.5 mg/kg uradil was injected intravenously; if SPI\u0026thinsp;\u0026ge;\u0026thinsp;50, 0.1ug/kg sufentanil was added; If the patient\u0026apos;s systolic blood pressure (SBP) decreases by more than 20% from baseline and persists for 5 minutes, administer phenylephrine 40\u0026ndash;80 \u0026micro;g intravenously; If the patient\u0026apos;s heart rate (HR) is \u0026le;\u0026thinsp;50 bpm, administer atropine 0.5 mg intravenously; if HR is \u0026ge;\u0026thinsp;100 bpm, administer esmolol 20\u0026ndash;30 mg intravenously; Monitor intraoperative blood loss and administer blood transfusion when clinically indicated; Intraoperative and postoperative: all patients received multimodal analgesia, including nonsteroidal anti-inflammatory drug hyperalgesia, nerve block and subcutaneous infiltration anaesthesia to prevent inadequate analgesia.\u003c/p\u003e\n \u003cp\u003eAdverse events defined as all adverse medical events occurring in subjects after receiving the investigational drug, which may manifest as symptoms, signs, diseases, or abnormal laboratory test results, but may not necessarily have a causal relationship with the investigational drug. All adverse events occurring in subjects during the trial, including abnormal laboratory test results, must be thoroughly investigated and followed up. All adverse events must be assessed for their nature, severity, and relationship to the drug, and strictly recorded in the case report form. The relationship between adverse events and the investigational drug is categorised as: definitely related, probably related, possibly related, possibly unrelated, or definitely unrelated. The incidence rate of adverse reactions is calculated using the categories \u0026lsquo;definitely related,\u0026rsquo; \u0026lsquo;probably related,\u0026rsquo; and \u0026lsquo;possibly related.\u0026rsquo; The severity or intensity of adverse events is classified into three levels: mild, moderate, and severe. In the event of a serious adverse reaction, it must be reported to the reporting unit within 24 hours, and the serious adverse event form must be completed.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\n \u003ch2\u003e2.10 Sample size calculation\u003c/h2\u003e\n \u003cp\u003eAccording to previous literature, the anticipated time to loss of consciousness (LOC) was estimated to be 62.96\u0026thinsp;\u0026plusmn;\u0026thinsp;13.32 s in Group P and 55.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.74 seconds in Group E [\u003cspan class=\"CitationRef\"\u003e9\u003c/span\u003e]. The level of significance (\u0026alpha;) was set at 0.05 (two-sided test) and statistical efficacy (1-\u0026beta;) at 90%. Sample size calculation was performed using PASS 2023 software. The results indicated a minimum requirement of 48 subjects per group. Accounting for a potential 20% dropout rate, we ultimately enrolled 120 participants in each group.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\n \u003ch2\u003e2.11 Statistical analysis\u003c/h2\u003e\n \u003cp\u003eStatistical analysis was performed using SPSS 26.0 software. Continuous variables such as time to loss of consciousness, hemodynamic parameters, drug dosage, postoperative recovery time, and serum hs-TnT levels were described using mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or median (interquartile range) based on whether they followed a normal distribution, and categorical variables such as successful induction of anesthesia and occurrence of adverse reactions were described using frequencies and percentages. T First, a baseline analysis was performed on the demographic characteristics of the enrolled cases in both groups to assess their balance and comparability. Subsequently, the efficacy and safety outcomes were compared between the two groups. For continuous variables between the experimental and control groups, comparisons were made using the independent samples t-test or Mann-Whitney U test, as appropriate. Categorical variables were compared using the chi-square (\u0026chi;\u0026sup2;) test or Fisher\u0026apos;s exact test. All statistical tests were two-sided, and a p-value\u0026thinsp;\u0026le;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eGiven the ongoing global population aging, the number of individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;60 years is expected to hit 2.1\u0026nbsp;billion by mid-century (2050) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The combination of osteoporosis, sarcopenia, and postural instability creates a high-risk triad for fragility fractures in aging populations. The number of hip fracture cases worldwide is projected to reach 4.5\u0026nbsp;million by 2050 [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Hip fractures are a leading cause of disability and are associated with high mortality rates, with one-year mortality reaching up to 30%[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. A hip fracture usually causes sharp pain in the front of the groin (sometimes spreading to the thigh or buttock), making standing impossible. The injured leg may appear turned outward or shorter. Radiographic confirmation is mandatory [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Surgery represents the first-line treatment for most cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, due to the physiological decline in elderly patients and their increased likelihood of multiple comorbidities, selecting appropriate anesthesia management is crucial. General anesthesia combined with nerve blocks is currently the most widely used approach,but elderly patients exhibit increased sensitivity to anesthetic agents, elevating the risk of intraoperative adverse events such as hypotension and hypoxemia. Therefore, particular attention must be paid to the selection of sedative agents.\u003c/p\u003e\u003cp\u003eEtomidate is a short-acting intravenous anesthetic agent. Beyond its advantages of rapid onset and quick recovery, etomidate demonstrates minimal cardiovascular impact, providing greater hemodynamic stability during induction and surgery while reducing the need for vasoactive drugs. These properties make it particularly suitable for anesthesia induction in elderly patients and those with cardiovascular compromise [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. However, etomidate may induce myoclonic movements, with reported incidence rates of 50\u0026ndash;80%. While these are typically transient and non-pathological, they may lead to severe consequences in specific patient populations (including those with full stomachs, malignant hypertension, aneurysms, or hyperkalemia). The precise therapeutic targets for prevention remain unclear [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Additionally, this medication may cause injection site pain and postoperative nausea and vomiting (PONV)[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] ,and meta-analyses demonstrate a significant association between etomidate induction and postoperative delirium (pooled OR 4.4)[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Morever, etomidate may additionally suppress 11β-hydroxylase activity, thereby interfering with adrenal corticosteroid synthesis. This pharmacological effect could potentially increase postoperative mortality risk in patients[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] .\u003c/p\u003e\u003cp\u003eFospropofol disodium (Lusedra), a sedative-hypnotic agent developed by Eisai Inc. (USA), received FDA approval in 2008 for inducing monitored anesthesia care (MAC) sedation in adult patients undergoing diagnostic or therapeutic procedures. Fospropofol was primarily indicated for sedation during bronchoscopy and gastrointestinal endoscopy, as well as outpatient minor surgeries. However, its requirement for anesthesiologist administration and limited advantages in ambulatory surgical settings contributed to poor market performance, ultimately leading to its market withdrawal in 2012. The newly approved fospropofol disodium is a water-soluble prodrug of propofol independently developed in China. Although both drugs share the same primary chemical component disodium 2,6-diisopropylphenoxymethyl phosphate, disodium salt (C₁₃H₁₉O₅PNa₂) - they differ in excipients, dosage forms, and manufacturing processes, which necessitates careful differentiation. Fospropofol disodium (2,6diisopropylphenoxymethyl phosphate, disodium salt) is inactive until converted by the body's alkaline phosphatase enzymes into active propofol (2,6-diisopropylphenol). Propofol activates GABA receptors on the postsynaptic membrane of central neurons, increasing chloride ion influx and reducing the excitability of the postsynaptic membrane. Simultaneously, it inhibits NMDA receptor-mediated calcium ion influx, suppressing postsynaptic neurons and producing sedative-hypnotic effects. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A previous Phase 1 clinical trial investigating the pharmacokinetics of fospropofol disodium injection in 10 healthy volunteers found that a single intravenous bolus dose of 10 mg/kg resulted in a maximum plasma concentration of propofol at 1.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.47 mg/mL, achieved in 10.06\u0026thinsp;\u0026plusmn;\u0026thinsp;2.63 minutes. The elimination half-life was 150.72\u0026thinsp;\u0026plusmn;\u0026thinsp;42.63 minutes, demonstrating linear pharmacokinetic characteristics[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. No severe adverse reactions were observed in either the Phase I or Phase II safety clinical trials of this drug [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Compared to induction with 2 mg/kg propofol, induction using 20 mg/kg fospropofol disodium resulted in a longer onset time and prolonged duration of anesthesia. In the fospropofol disodium group, the time to achieve an MOAA/S score of 1 and loss of eyelash reflex was 3.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7 min, while the recovery time was 37\u0026thinsp;\u0026plusmn;\u0026thinsp;9 min [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], which suggests that fospropofol disodium may be suitable for anesthesia induction in patients who do not require rapid onset and are undergoing relatively prolonged surgical procedures. In a multicenter Phase III clinical study, fospropofol disodium injection demonstrated comparable anesthesia induction success rates to propofol, while reducing the risk of myocardial suppression and effectively avoiding injection pain[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Currently, there are relatively few prospective clinical trials on fospropofol disodium, and no studies have yet investigated its efficacy and safety compared to etomidate for anesthesia induction in elderly patients undergoing hip surgery.. The recommended induction dosage of fospropofol disodium for adults is 10\u0026ndash;15 mg/kg according to current guidelines [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. However, considering the lower plasma protein levels in elderly patients, which result in reduced bound drug concentrations and increased free drug concentrations, this study used the minimum induction dose of 10 mg/kg of fospropofol disodium for induction.\u003c/p\u003e\u003cp\u003eFirst, this study was limited to elderly patients undergoing hip surgery, which may restrict the generalizability of the findings. Future research should expand to include other surgical populations (e.g., abdominal or cardiovascular surgeries) to validate the applicability of the results. Second, as a single-center study with a relatively small sample size (n\u0026thinsp;=\u0026thinsp;120), the statistical power may be insufficient, potentially affecting the robustness of the conclusions. Therefore, further multicenter, large-scale randomized controlled trials are warranted to enhance the external validity and reliability of the findings\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics Committee of the First People\u0026apos;s Hospital of Changzhou\u003cem\u003e.\u0026nbsp;\u003c/em\u003eWritten, informed consent to participate will be obtained from all\u003cem\u003e\u0026nbsp;\u003c/em\u003eparticipants.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data for this study are available from the corresponding author for valid reasons.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was not funded\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWLL was responsible for experimental design, figure preparation, and manuscript drafting; YHW was responsible for study conceptualization and manuscript editing; LQ supervised research quality and critically revised the manuscript. All authors discussed results and approved the final version.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eRoberts KC, Brox WT. AAOS Clinical Practice Guideline: Management of Hip Fractures in the Elderly. J Am Acad Orthop Surg. 2015;23(2):138-40.\u003c/li\u003e\n\u003cli\u003eSaugel B, Sessler DI. Perioperative Blood Pressure Management. Anesthesiology. 2021;134(2):250-61.\u003c/li\u003e\n\u003cli\u003eSong JC, Lu ZJ, Jiao YF, Yang B, Gao H, Zhang J, et al. Etomidate Anesthesia during ERCP Caused More Stable Haemodynamic Responses Compared with Propofol: A Randomized Clinical Trial. Int J Med Sci. 2015;12(7):559-65.\u003c/li\u003e\n\u003cli\u003eMullick P, Talwar V, Aggarwal S, Prakash S, Pawar M. Comparison of priming versus slow injection for reducing etomidate-induced myoclonus: a randomized controlled study. Korean J Anesthesiol. 2018;71(4):305-10.\u003c/li\u003e\n\u003cli\u003eSneyd JR, Valk BI. Etomidate and its derivatives: time to say goodbye? Br J Anaesth. 2025;134(1):11-3.\u003c/li\u003e\n\u003cli\u003eZhang H, Wu A, Nan X, Yang L, Zhang D, Zhang Z, et al. The Application and Pharmaceutical Development of Etomidate: Challenges and Strategies. Mol Pharm. 2024;21(12):5989-6006.\u003c/li\u003e\n\u003cli\u003eWu CM, Zhang WS, Liu J, Zhang WY, Ke BW. Efficacy and Safety of Fospropofol Disodium for Injection in General Anesthesia Induction for Adult Patients: A Phase 3 Trial. Front Pharmacol. 2021;12:687894.\u003c/li\u003e\n\u003cli\u003eA-W C, JM T, PC G, DG A, H M, J B, et al. SPIRIT 2013 Explanation and Elaboration: Guidance for protocols of clinical trials. BMJ. 2013:346:e7586.\u003c/li\u003e\n\u003cli\u003eSi Y, Feng J, Xia L. The efficacy of fospropofol disodium in general anesthesia induction for elderly ureteroscopic lithotripsy patients. HENAN JOUＲNAL OF SUＲGEＲY 2024.\u003c/li\u003e\n\u003cli\u003eCheung EYN, Tan KCB, Cheung CL, Kung AWC. Osteoporosis in East Asia: Current issues in assessment and management. Osteoporos Sarcopenia. 2016;2(3):118-33.\u003c/li\u003e\n\u003cli\u003eBerry JM, Merin RG. Etomidate myoclonus and the open globe. Anesth Analg. 1989;69(2):256-9.\u003c/li\u003e\n\u003cli\u003eSchroeder JD, Turner SP, Buck E. Hip Fractures: Diagnosis and Management. Am Fam Physician. 2022;106(6):675-83.\u003c/li\u003e\n\u003cli\u003eLeBlanc KE, Muncie HL, Jr., LeBlanc LL. Hip fracture: diagnosis, treatment, and secondary prevention. Am Fam Physician. 2014;89(12):945-51.\u003c/li\u003e\n\u003cli\u003eXia Z, Kamra K, Dong J, Harp KA, Xiong Y, Lisco SJ, et al. Comparison of efficacy and safety of etomidate with other anesthesia induction drugs for patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized controlled trials. Heliyon. 2024;10(22):e38274.\u003c/li\u003e\n\u003cli\u003eFeng Y, Cheng YX, Wang XH. Etomidate-Induced myoclonus in Sprague‒Dawley rats involves the activation of neocortical Calpain-2 and its decrement on KCC2 protein. BMC Anesthesiol. 2025;25(1):213.\u003c/li\u003e\n\u003cli\u003eHe M, Zhu Z, Jiang M, Liu X, Wu R, Zhou J, et al. Risk Factors for Postanesthetic Emergence Delirium in Adults: A Systematic Review and Meta-analysis. J Neurosurg Anesthesiol. 2024;36(3):190-200.\u003c/li\u003e\n\u003cli\u003ePreziosi P, Vacca M. Adrenocortical suppression and other endocrine effects of etomidate. Life Sci. 1988;42(5):477-89.\u003c/li\u003e\n\u003cli\u003eMarik PE. Propofol: therapeutic indications and side-effects. Curr Pharm Des. 2004;10(29):3639-49.\u003c/li\u003e\n\u003cli\u003eY. YL, L. R, X. Y, P. XX, S. QG, Y K. The Pharmacokinetic Study of the Active Metabolite of HX0507 in Healthy Volunteer. West China J Pharm Sci. 2012:298\u0026ndash;301.\u003c/li\u003e\n\u003cli\u003eYi XQ, Li R, Zhang WS, Liu J, Xu J, Liao TZ. [Effect of single doses of HX0507 on QTc intervals in healthy people: a phase I safety and tolerability study]. Sichuan Da Xue Xue Bao Yi Xue Ban. 2012;43(6):868-72.\u003c/li\u003e\n\u003cli\u003eLiu R, Luo C, Liu J, Zhang W, Li Y, Xu J. Efficacy and Safety of FospropofolFD Compared to Propofol When Given During the Induction of General Anaesthesia: A Phase II, Multi-centre, Randomized, Parallel-Group, Active-Controlled, Double-Blind, Double-Dummy Study. Basic Clin Pharmacol Toxicol. 2016;119(1):93-100.\u003c/li\u003e\n\u003cli\u003eJ L. Guidance on the clinical application of fospropofol disodium. Chinese J Anesthesio. 2023;43:912\u0026ndash;5.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"fospropofol disodium, induction of anaesthesia, elderly hip surgery","lastPublishedDoi":"10.21203/rs.3.rs-7053501/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7053501/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFospropofol disodium is a novel water-soluble prodrug of propofol. This randomized controlled trial aimed to compare the efficacy and safety of fospropofol disodium versus etomidate for anesthesia induction in elderly patients undergoing hip surgery.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e \u003cstrong\u003eand analysis.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis single-center, randomized, double-blind, controlled trial. It will enroll 120 elderly patients scheduled for hip surgery. Participants will be randomized in a 1:1 ratio to either the fospropofol disodium group (Group P) or the etomidate group (Group E). All patients will receive intravenous anesthesia induction with either fospropofol disodium or etomidate, according to their randomized group assignment. We will collect the following data，including: the time to loss of consciousness；the success rate of anesthesia induction; the incidence of injection pain, myoclonus, and sensory abnormalities within 30 seconds after initial dose administration; intraoperative hemodynamic stability; total intraoperative consumption of opioids, propofol, and vasoactive drugs; postoperative recovery time; the incidence of postoperative nausea and vomiting within 48 hours postoperatively; the incidence of postoperative delirium within 48 hours postoperatively; and serum high-sensitivity troponin T (hs-TnT) levels within 48 hours postoperatively. Data will be analyzed on an intention-to-treat basis and Per Protocol Analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiscussion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe hypothesized that: fospropofol disodium would be clinically effective for anesthesia induction in elderly hip surgery patients; its hemodynamic stability would be non-inferior to etomidate; and it would demonstrate a superior safety profile with fewer adverse effects compared to etomidate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial registration\u003c/strong\u003e: The UK’s Clinical Study Registry ( ISRCTN registry ) https://www.isrctn.com/ISRCTN12170320 registration number: ISRCTN12170320 Date:01/07/2025\u003c/p\u003e","manuscriptTitle":"Exploration of the effects of fospropofol disodium in anesthesia induction for elderly hip surgery: A study protocol for a Clinical Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-22 19:34:06","doi":"10.21203/rs.3.rs-7053501/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":"3b5f939b-486b-4a36-a96b-78519a769e66","owner":[],"postedDate":"October 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-24T09:07:39+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-22 19:34:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7053501","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7053501","identity":"rs-7053501","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}