Effects of remimazolam on hemodynamics in children with congenital heart disease

Effects of remimazolam on hemodynamics in children with congenital heart disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Effects of remimazolam on hemodynamics in children with congenital heart disease Hongyun Li, Zhaomeng Song, Xunwei Jiang, Wei Liu, Jinxia Wang, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6858449/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 Maintaining hemodynamic stability during anesthesia is crucial for patients with congenital heart disease. Remimazolam, a novel benzodiazepine, offers advantages, such as rapid onset, quick recovery, stable hemodynamics, and mild respiratory depression. We aimed to assess the effects of a single intravenous dose of remimazolam on hemodynamics in children with congenital heart disease. Between June and September 2024, 40 children undergoing elective cardiac catheterization and transcatheter closure at Shanghai Children's Hospital were included. Non-invasive (heart rate, blood pressure, oxygen saturation) and invasive hemodynamic parameters (cardiac output, cardiac index, vena cava pressure, right atrial pressure, right ventricular pressure, pulmonary artery pressure) were measured before and after intravenous administration of 0.3 mg/kg remimazolam. Hemodynamic changes were compared pre- and post-treatment. Five patients were excluded due to incomplete data, leaving 35 for analysis (sex, 11 male, 24 female; median age, 6.67 [interquartile range: 4–11.5 years]). No significant changes in non-invasive or invasive hemodynamic parameters were observed after remimazolam administration. Additionally, no adverse effects, such as bradycardia, hypotension, or hypertension, occurred. A single intravenous dose of 0.3 mg/kg remimazolam did not affect hemodynamic parameters in children with congenital heart disease, providing stable hemodynamics with minimal circulatory fluctuations. Health sciences/Cardiology Health sciences/Medical research Remimazolam child hemodynamics congenital heart defects anesthesia Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Children with congenital heart disease (CHD) are at increased risk of hemodynamic instability during general anesthesia. Anesthesia induction in these patients prioritizes maintaining hemodynamic stability, controlling myocardial oxygen consumption, and minimizing procedural stress 1 . Currently, propofol and etomidate are commonly used for anesthesia induction in pediatric patients with CHD. While propofol is a rapid-acting sedative that allows quick recovery, it is associated with a high incidence of hypotension, bradycardia, and injection pain 2 , 3 . Etomidate exerts minimal effects on hemodynamics and does not cause dose-dependent hypotension 4 ; however, it carries risks of adrenal suppression and myoclonus 5 , 6 . Remimazolam, a novel ultra-short-acting benzodiazepine, offers several advantages over propofol and etomidate, including rapid onset, fast metabolism, hemodynamic stability, minimal circulatory fluctuation, mild respiratory depression and reversibility 7 , 8 . Compared to propofol, remimazolam has a lower risk of cardiovascular depression, respiratory depression, and injection pain 7 , 8 . Similarly, compared to etomidate, it is associated with less injection pain and reduces myoclonus 6 . Remimazolam has been used safely as a sedative and anesthetic in patients with cardiac disease 9 , including those with aortic valve stenosis 10 , those undergoing valve replacement 11 , or those undergoing radiofrequency ablation for atrial fibrillation 12 . Moreover, it has been employed during cardiovascular procedures 13 and various diagnostic and interventional procedures 14 . However, there is limited research on the effects of remimazolam on hemodynamic parameters in children with CHD. Therefore, in this prospective observational study, we aimed to evaluate these effects by comparing hemodynamic changes before and after a single administration of remimazolam. Results Characteristics and Demographic Data of the Patients A total of 40 pediatric patients were recruited according to the inclusion and exclusion criteria. Due to incomplete data from five patients, 35 were included in the final analysis: 11 male and 24 female individuals, with a median age of 6.67 (IQR: 4–11.5) years, median weight of 20.5 kg (IQR: 15–35), and median body mass index (BMI) of 15.28 kg/m² (IQR: 13.97–16.96). Among them, 20 had atrial septal defects (ASD), eight had ventricular septal defects (VSD), six had patent ductus arteriosus (PDA), and one (female, 2.25 years old, 15 kg, BMI 15.94) had both ASD and VSD. Baseline characteristics are presented in Table 1 . Table 1 Baseline clinical characteristics of the study participants Variable All (N = 35) VSD (N = 8) PDA (N = 6) ASD (N = 20) Sex Female 24 (68.57%) 3 (37.5%) 4 (66.67%) 16 (80%) Male 11 (31.43%) 5 (62.5%) 2 (33.33%) 4 (20%) Age (years) 6.67 (4–11.5) 4.46 (3.00–6.71) 5.92 (3.27–9.12) 7.38 (5.40–13.69) Weight (kg) 20.5 (15–35) 17(15–20.38) 19.25 (15–24.13) 27.75 (16.13–52.38) BMI (kg/m 2 ) 15.28 (13.97–16.96) 15.12 (14.38–16.02) 14.26 (13.36–16.21) 15.88 (13.93–20.45) ASD, atrial septal defect; PDA, patent ductus arteriosus; VSD, ventricular septal defect Hemodynamic Parameter Changes No significant fluctuations were observed in HR or MAP following intravenous administration of remimazolam, with changes remaining below 20% (Fig. 2 ). Only one patient with VSD showed a 20% increase in CO and CI post-remimazolam administration, with no significant differences observed across all patients (Fig. 3 ). Additionally, there were no significant differences in invasive pressure measurements, including SVCP, RAP, RVP, and PAP (Table 2 ). Table 2 Comparison of hemodynamic variables before and after administration of remimazolam in all patients Variable Pre- remimazolam Post- remimazolam p-value HR (bpm) 104.31 ± 20.27 104.91 ± 19.76 0.485 MAP (mmHg) 61 (58–65) 61 (57–66) 0.313 CO (L/min) 3.2 (2.34–3.5) 3 (2.41–3.7) 0.133 CI (L/min/m 2 ) 3.3 (3–3.6) 3.3 (3–3.71) 0.292 mSVCP (mmHg) 8 (6–11) 9 (6–10.5) 0.173 mRAP (mmHg) 8 (6–10) 8.5 (6.75–10.25) 0.064 mRVP (mmHg) 9 (6–12) 9 (16–11.25) 0.877 mPAP (mmHg) 15.5 (14–19) 16 (14–19.5) 0.517 The level of significance was set at *p < 0.05 HR, heart rate; BP, blood pressure; CO, cardiac output; CI, cardiac index; SVCP, superior vena cava pressure; RAP, right atrial pressure; RVP, right ventricular pressure; PAP, pulmonary artery pressure; mPAP, mean pulmonary artery pressure Secondary Outcomes Pulmonary hypertension was defined as mPAP > 20 mmHg.15 Five patients met this criterion prior to remimazolam administration. No significant changes in mPAP were observed pre- and post-treatment in these patients (p = 0.750, Table 3 ). Similarly, in the overall cohort of 35 patients, there was no significant difference in mPAP following a single intravenous injection of remimazolam (p = 0.517, Fig. 4 ). Importantly, no adverse events, such as bradycardia, hypotension, or hypertension, were reported. Table 3 Changes in mPAP in patients with pulmonary hypertension before and after administration of remimazolam (N = 5) Diagnosis mPAP (mmHg) pre-remimazolam mPAP (mmHg) post-remimazolam PDA 35 37 VSD 52 45 PDA 23 21 ASD 21 21 ASD 27 27 mPAP, mean pulmonary artery pressure Discussion This study evaluated the effects of a single intravenous injection of remimazolam on hemodynamic parameters in children with CHD undergoing cardiac catheterization. No significant differences were observed in non-invasive (HR, MAP, CO, CI) or invasive parameters (mSVCP, mRAP, mRVP, mPAP) before and after administration of 0.3 mg·kg⁻¹ remimazolam. Additionally, no adverse events, such as bradycardia, hypotension, or hypertension, occurred. In this study, a multi-parameter cardiac monitor was used to continuously assess HR and MAP. The changes in HR and MAP before and after administration of remimazolam were compared, and fluctuations remained below 20%, indicating that remimazolam had minimal impact on these parameters. In contrast, Kimoto et al. 16 reported that 75.2% of patients experienced MAP changes > 20% from baseline, and 53% exhibited HR changes > 20% during general anesthesia. The differences between this study and previous findings are likely attributable to variations in methodology. In the present study, remimazolam was administered as a single bolus dose during anesthesia, whereas in studies such as that by Kimoto et al. 16 , the drug was administered continuously via infusion. It is hypothesized that differences in dosing strategy and timing may influence hemodynamic outcomes. Additionally, the accuracy of baseline data in pediatric patients may be affected by agitation or crying prior to anesthesia induction. Nonetheless, the results of this study support the use of a single intravenous injection of remimazolam as a safe and stable option for children undergoing cardiac catheterization and transcatheter closure. Anesthetic management in children with CHD requires careful medication selection to preserve hemodynamic and electrophysiological stability 17 . In this study, a non-invasive CO monitor was used for continuous CO and CI assessment, offering a minimally invasive approach. No significant changes in CO or CI were observed post-remimazolam administration. Previous studies have supported the hemodynamic stability of remimazolam; Tang et al. 18 reported reduced fluctuations via stress response modulation and enhanced myocardial contractility, while Qiu et al. 19 noted minimal effects on BP. Both non-invasive and invasive hemodynamic parameters were assessed. Following general anesthesia, routine right heart catheterization (femoral vein → SVC → RA → RV → PA) was performed, and cross-sectional pressures and blood gases were measured. These procedures are standard practice and did not introduce additional trauma. At 3 min after administration of 0.3 mg·kg⁻¹ remimazolam, pressures were re-measured. Comparative analysis revealed no significant changes in mSVCP, mRAP, mRVP, or mean PAP. These findings are consistent with the known characteristics of remimazolam, including hemodynamic stability, minimal circulatory fluctuation, mild respiratory depression, and reversibility 20 , 21 . Pulmonary hypertension (PH) is a critical indicator in CHD, guiding decisions regarding surgical or interventional treatment and assessing long-term outcomes. As survival rates improve, the prevalence of CHD-related PH is expected to rise 22 . PH is defined as resting mPAP > 20 mmHg, as measured by right heart catheterization 15 . In this study, five patients had PH prior to remimazolam administration. No significant change in mPAP was observed post-treatment. Similarly, among patients without PH, mPAP remained stable. These findings indicate that a single dose of remimazolam does not significantly affect mPAP in patients with or without PH. This study had limitations. First, it was a single-center study with a limited sample size. Second, only pre- and post-intervention comparisons were conducted without inclusion of comparator drug groups, limiting assessment of remimazolam’s advantages over traditional sedatives. Third, the study focused solely on children undergoing catheter-based procedures, excluding those undergoing open-heart surgery. Future studies should involve larger, multicenter cohorts and explore broader CHD populations. In conclusion, a single intravenous injection of remimazolam at 0.3 mg·kg⁻¹ demonstrates minimal impact on hemodynamics and does not alter mean PAP in children with CHD undergoing cardiac catheterization and transcatheter closure. Remimazolam appears to provide hemodynamic stability and minimal circulatory fluctuation in this patient population. Methods Study Design and Patients This study evaluated the effects of a single intravenous injection of remimazolam on the hemodynamic parameter changes in children with CHD. The study was a single-center, prospective, observational, self-controlled study, approved by the Ethics Committee of Shanghai Children's Hospital (2024R059-F01) and registered at the Chinese Clinical Trial Registry (chictr.org.cn; Registration No.: ChiCTR2400084993, Registration Date: May 29, 2024). All procedures were carried out in accordance with the Declaration of Helsinki. Informed consent was obtained from the parents of 40 children with CHD who were scheduled to undergo cardiac catheterization and transcatheter closure. However, due to incomplete data from five patients, only 35 patients were included in the final analysis. The study flow is illustrated in Fig. 1 . Inclusion and Exclusion Criteria The inclusion criteria were as follows: age < 18 years with American Society of Anesthesiologists (ASA) classification II or III and no premedication. Patients meeting these criteria were scheduled for elective cardiac catheterization and transcatheter closure under general anesthesia. Patients were excluded if they had a known allergy to benzodiazepines, were taking sedatives or anticonvulsant medications, or had a history of liver or kidney dysfunction or other systemic complications prior to the procedure. Anesthesia Induction and Maintenance Routine intraoperative monitoring was performed using a multi-parameter electrocardiogram monitor (Model AM, Serial No. 6955816; DIVA Laboratories Ltd., Taipei, Taiwan) to assess electrocardiogram, non-invasive blood pressure (BP), and oxygen saturation (SpO₂). Continuous monitoring of cardiac output (CO) and cardiac index (CI) was conducted using a non-invasive CO monitor (Model ICON(C3); Shanghai Meta Care Medical Device Co. Ltd., Shanghai, China). Anesthesia Induction Anesthesia was induced intravenously with glycopyrrolate 4 µg/kg (maximum 100 µg), propofol 2–3 mg/kg, rocuronium 0.6 mg/kg, and sufentanil 0.2 µg/kg. Following induction, a laryngeal mask airway was inserted to facilitate mechanical ventilation. Anesthesia Maintenance Anesthesia was maintained with pressure-controlled ventilation, targeting an end-tidal CO₂ (EtCO₂) of 35–45 mmHg. Sevoflurane (2–3%) was continuously inhaled to maintain a minimum alveolar concentration of 1–1.3. Data Measurement and Classifications After establishing general anesthesia and initiating mechanical ventilation, continuous monitoring of heart rate (HR), BP, SpO₂, CO, and CI was performed. During cardiac catheterization, anesthesiologists recorded invasive hemodynamic parameters including superior vena cava pressure (SVCP), right atrial pressure (RAP), right ventricular pressure (RVP), and pulmonary artery pressure (PAP). Remimazolam Tosilate for Injection (Jiangsu Hengrui Pharmaceuticals Co., Ltd., Beijing, China; 25 mg/vial; Batch No: 231123AK; National Drug Approval No: H20217078) was administered intravenously at a dose of 0.3 mg/kg. Three minutes after administration, all parameters were re-measured. The primary outcome was the change in hemodynamic parameters pre- and post-administration. Secondary outcomes included mean PAP (mPAP) and adverse cardiovascular events, such as bradycardia, hypotension, and hypertension. Bradycardia was defined as HR ≤ 50 bpm and treated with atropine 0.01 mg/kg IV. Hypotension was defined as a ≥ 30% reduction in mean arterial pressure (MAP) from baseline and was confirmed if unresponsive to ephedrine. Hypertension was defined as a ≥ 30% increase in MAP from baseline; if unresponsive to deepened anesthesia, it was confirmed. Rescue medications during the peri-anesthetic period included atropine (0.01 mg/kg) and epinephrine (0.01 mg/kg). Statistical Analysis Data were analyzed using SPSS software (version 26.0; IBM Corp., Amonk, NY, USA). Normality was assessed using the Shapiro–Wilk test. Normally distributed data are presented as meanS ± standard deviationS; non-normally distributed data as medianS (interquartile rangeS) [M (IQR)]. Paired t-tests or Wilcoxon signed-rank tests were used to compare pre- and post-treatment values. A p-value < 0.05 was considered statistically significant. Declarations Acknowledgments: This study was supported by doctors and technicians at the department of cardiology and Department of Imaging, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University. Funding : Support was provided solely by institutional and departmental sources. Author contributions: Hongyun Li：Write articles ，contributions in terms of conception and design, data acquisition and data analysis； Xunwei Jiang and Wei Liu ：Contributions in surgical operation, measurement of pressure at each cross-section of the heart ； Jinxia Wang：Application of statistical； Yan Jiang：Contributions in design of methodology，Draft articles ， make critical revisions to important knowledge-based content； Rong Wei：Formulation of overarching research goals，critical review, commentary or revision – including pre-or post publication stages. Competing interests : The authors declare no competing interests. Data availability: The datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Consent statement: Informed consent was obtained from the parents of 40 children with CHD who were scheduled to undergo cardiac catheterization and transcatheter closure. Clinical trial number and registry URL: ChiCTR2400084993, https://www.chictr.org.cn/ References Lee, S. H. et al. Efficacy of Single-Bolus Administration of Remimazolam During Induction of Anesthesia in Patients Undergoing Cardiac Surgery: A Prospective, Single-Center, Randomized Controlled Study. Anesth Analg 139 , 770–780 (2024). Fleck, T. et al. Propofol effect on cerebral oxygenation in children with congenital heart disease. Pediatr. Cardiol. 36 , 543–549 (2015). Vullo, P. A., Real Navacerrada, M., Í., I. & Navarro Suay, R. Hemodynamic impact of increasing time between fentanyl and propofol administration during anesthesia induction: a randomised, clinical trial. Braz J. Anesthesiol . 74 , 744230 (2024). Spanos, A., Chiu, H. H. & Tye, C. Y. Effects of etomidate given in repeated doses. Anaesth. Intensive Care . 6 , 337–341 (1978). Komatsu, R. et al. 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Effect of remimazolam induction on hemodynamics in patients undergoing valve replacement surgery: A randomized, double-blind, controlled trial. Pharmacol. Res. Perspect. 9 , e00851 (2021). Nam, S. W. et al. Effects of remimazolam on hemodynamic changes during cardiac ablation for atrial fibrillation under general anesthesia: a propensity-score-matched retrospective cohort study. Can. J. Anaesth. 70 , 1495–1503 (2023). Aoki, Y. et al. Association between remimazolam and postoperative delirium in older adults undergoing elective cardiovascular surgery: a prospective cohort study. J. Anesth. 37 , 13–22 (2023). Gillis, H., McKee, C., Chenault, K., Corridore, M. & Tobias, J. D. Preliminary experience with remimazolam for procedural sedation and as an adjunct to general anesthesia during diagnostic and interventional cardiac procedures. Cardiol. Res. 15 , 12–17 (2024). Humbert, M. et al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur. Heart J. 43 , 3618–3731 (2022). Kimoto, Y., Hirano, T., Kuratani, N., Cavanaugh, D. & Mason, K. P. Remimazolam as an Adjunct to General Anesthesia in Children: Adverse Events and Outcomes in a Large Cohort of 418 Cases. J. Clin. Med. 12 , 3930 (2023). Lam, J. E., Lin, E. P., Alexy, R. & Aronson, L. A. Anesthesia and the pediatric cardiac catheterization suite: a review. Paediatr. Anaesth. 25 , 127–134 (2015). Tang, F. et al. Remimazolam benzenesulfonate anesthesia effectiveness in cardiac surgery patients under general anesthesia. World J. Clin. Cases . 9 , 10595–10603 (2021). Qiu, Y., Gu, W., Zhao, M., Zhang, Y. & Wu, J. The hemodynamic stability of remimazolam compared with propofol in patients undergoing endoscopic submucosal dissection: A randomized trial. Front. Med. (Lausanne) . 9 , 938940 (2022). Sneyd, J. R., Gambus, P. L. & Rigby-Jones, A. E. Current status of perioperative hypnotics, role of benzodiazepines, and the case for remimazolam: a narrative review. Br. J. Anaesth. 127 , 41–55 (2021). Gao, Y. Q. et al. Pharmacokinetics of remimazolam after intravenous infusion in anaesthetised children. Br. J. Anaesth. 131 , 914–920 (2023). Ntiloudi, D., Zanos, S., Gatzoulis, M. A., Karvounis, H. & Giannakoulas, G. How to evaluate patients with congenital heart disease-related pulmonary arterial hypertension. Expert Rev. Cardiovasc. Ther. 17 , 11–18 (2019). Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6858449","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":483053003,"identity":"4b7fbd39-1eaa-4567-9cf5-dbbca5e1d412","order_by":0,"name":"Hongyun Li","email":"","orcid":"","institution":"Shanghai Jiao Tong University","correspondingAuthor":false,"prefix":"","firstName":"Hongyun","middleName":"","lastName":"Li","suffix":""},{"id":483053004,"identity":"ad9599ce-8daa-4c71-af8a-7a2ffcf9a7cf","order_by":1,"name":"Zhaomeng Song","email":"","orcid":"","institution":"Shanghai Jiao Tong 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10:27:43","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":73474,"visible":true,"origin":"","legend":"\u003cp\u003eAbsolute value changes in heart rate (\u003cem\u003eleft\u003c/em\u003e) and mean arterial pressure (\u003cem\u003eright\u003c/em\u003e) in 35 pediatric patients before and after administration of 0.3 mg/kg remimazolam.\u003c/p\u003e","description":"","filename":"Figure2.png","url":"https://assets-eu.researchsquare.com/files/rs-6858449/v1/7a36c6aaee9dc127fbc5de03.png"},{"id":86662545,"identity":"ad577c16-29c4-4208-bb8c-cbff1a57ee4d","added_by":"auto","created_at":"2025-07-14 10:43:43","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":61767,"visible":true,"origin":"","legend":"\u003cp\u003eAbsolute value changes in cardiac output rate (\u003cem\u003eleft\u003c/em\u003e) and cardiac index (right) in 35 pediatric patients before and after administration of 0.3 mg/kg remimazolam.\u003c/p\u003e","description":"","filename":"Figure3.png","url":"https://assets-eu.researchsquare.com/files/rs-6858449/v1/1b7393f3764fbe1ed8d582da.png"},{"id":86658859,"identity":"647c10e1-e677-44c5-8526-78151d406b9f","added_by":"auto","created_at":"2025-07-14 10:27:43","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":26692,"visible":true,"origin":"","legend":"\u003cp\u003eAbsolute value changes in mean pulmonary artery pressure (mPAP) of 35 pediatric patients before and after administration of 0.3 mg/kg remimazolam.\u003c/p\u003e","description":"","filename":"Figure4.png","url":"https://assets-eu.researchsquare.com/files/rs-6858449/v1/1ff7c87136b3ca74b94fbb2b.png"},{"id":88400974,"identity":"7f2408c5-a904-4bff-8a2f-f1d1fa5d292d","added_by":"auto","created_at":"2025-08-06 06:54:15","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":813107,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6858449/v1/b4880bdd-061b-48f9-a5fd-9c89ee760fdf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effects of remimazolam on hemodynamics in children with congenital heart disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eChildren with congenital heart disease (CHD) are at increased risk of hemodynamic instability during general anesthesia. Anesthesia induction in these patients prioritizes maintaining hemodynamic stability, controlling myocardial oxygen consumption, and minimizing procedural stress \u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Currently, propofol and etomidate are commonly used for anesthesia induction in pediatric patients with CHD. While propofol is a rapid-acting sedative that allows quick recovery, it is associated with a high incidence of hypotension, bradycardia, and injection pain \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Etomidate exerts minimal effects on hemodynamics and does not cause dose-dependent hypotension \u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e; however, it carries risks of adrenal suppression and myoclonus \u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eRemimazolam, a novel ultra-short-acting benzodiazepine, offers several advantages over propofol and etomidate, including rapid onset, fast metabolism, hemodynamic stability, minimal circulatory fluctuation, mild respiratory depression and reversibility \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Compared to propofol, remimazolam has a lower risk of cardiovascular depression, respiratory depression, and injection pain \u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Similarly, compared to etomidate, it is associated with less injection pain and reduces myoclonus \u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eRemimazolam has been used safely as a sedative and anesthetic in patients with cardiac disease \u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e, including those with aortic valve stenosis \u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e, those undergoing valve replacement \u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e, or those undergoing radiofrequency ablation for atrial fibrillation \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e. Moreover, it has been employed during cardiovascular procedures \u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u003c/sup\u003e and various diagnostic and interventional procedures \u003csup\u003e\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eHowever, there is limited research on the effects of remimazolam on hemodynamic parameters in children with CHD. Therefore, in this prospective observational study, we aimed to evaluate these effects by comparing hemodynamic changes before and after a single administration of remimazolam.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eCharacteristics and Demographic Data of the Patients\u003c/h2\u003e\u003cp\u003eA total of 40 pediatric patients were recruited according to the inclusion and exclusion criteria. Due to incomplete data from five patients, 35 were included in the final analysis: 11 male and 24 female individuals, with a median age of 6.67 (IQR: 4\u0026ndash;11.5) years, median weight of 20.5 kg (IQR: 15\u0026ndash;35), and median body mass index (BMI) of 15.28 kg/m\u0026sup2; (IQR: 13.97\u0026ndash;16.96). Among them, 20 had atrial septal defects (ASD), eight had ventricular septal defects (VSD), six had patent ductus arteriosus (PDA), and one (female, 2.25 years old, 15 kg, BMI 15.94) had both ASD and VSD. Baseline characteristics are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline clinical characteristics of the study participants\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eAll (N\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eVSD (N\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003ePDA (N\u0026thinsp;=\u0026thinsp;6)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eASD (N\u0026thinsp;=\u0026thinsp;20)\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eSex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24 (68.57%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3 (37.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (66.67%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e16 (80%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (31.43%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e5 (62.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (33.33%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e4 (20%)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eAge (years)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.67 (4\u0026ndash;11.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.46 (3.00\u0026ndash;6.71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.92 (3.27\u0026ndash;9.12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.38 (5.40\u0026ndash;13.69)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eWeight (kg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20.5 (15\u0026ndash;35)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17(15\u0026ndash;20.38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19.25 (15\u0026ndash;24.13)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27.75 (16.13\u0026ndash;52.38)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e\u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.28 (13.97\u0026ndash;16.96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15.12 (14.38\u0026ndash;16.02)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.26 (13.36\u0026ndash;16.21)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e15.88 (13.93\u0026ndash;20.45)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eASD, atrial septal defect; PDA, patent ductus arteriosus; VSD, ventricular septal defect\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eHemodynamic Parameter Changes\u003c/h3\u003e\n\u003cp\u003eNo significant fluctuations were observed in HR or MAP following intravenous administration of remimazolam, with changes remaining below 20% (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eOnly one patient with VSD showed a 20% increase in CO and CI post-remimazolam administration, with no significant differences observed across all patients (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAdditionally, there were no significant differences in invasive pressure measurements, including SVCP, RAP, RVP, and PAP (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eComparison of hemodynamic variables before and after administration of remimazolam in all patients\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVariable\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePre- remimazolam\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003ePost- remimazolam\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ep-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHR (bpm)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e104.31\u0026thinsp;\u0026plusmn;\u0026thinsp;20.27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e104.91\u0026thinsp;\u0026plusmn;\u0026thinsp;19.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.485\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMAP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e61 (58\u0026ndash;65)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e61 (57\u0026ndash;66)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.313\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCO (L/min)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.2 (2.34\u0026ndash;3.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3 (2.41\u0026ndash;3.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.133\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCI (L/min/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.3 (3\u0026ndash;3.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.3 (3\u0026ndash;3.71)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.292\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emSVCP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (6\u0026ndash;11)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (6\u0026ndash;10.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.173\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emRAP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8 (6\u0026ndash;10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.5 (6.75\u0026ndash;10.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.064\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emRVP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9 (6\u0026ndash;12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (16\u0026ndash;11.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.877\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003emPAP (mmHg)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15.5 (14\u0026ndash;19)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16 (14\u0026ndash;19.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0.517\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eThe level of significance was set at *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"4\"\u003eHR, heart rate; BP, blood pressure; CO, cardiac output; CI, cardiac index; SVCP, superior vena cava pressure; RAP, right atrial pressure; RVP, right ventricular pressure; PAP, pulmonary artery pressure; mPAP, mean pulmonary artery pressure\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\n\u003ch3\u003eSecondary Outcomes\u003c/h3\u003e\n\u003cp\u003ePulmonary hypertension was defined as mPAP\u0026thinsp;\u0026gt;\u0026thinsp;20 mmHg.15 Five patients met this criterion prior to remimazolam administration. No significant changes in mPAP were observed pre- and post-treatment in these patients (p\u0026thinsp;=\u0026thinsp;0.750, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). Similarly, in the overall cohort of 35 patients, there was no significant difference in mPAP following a single intravenous injection of remimazolam (p\u0026thinsp;=\u0026thinsp;0.517, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Importantly, no adverse events, such as bradycardia, hypotension, or hypertension, were reported.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eChanges in mPAP in patients with pulmonary hypertension before and after administration of remimazolam (N\u0026thinsp;=\u0026thinsp;5)\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiagnosis\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003emPAP (mmHg) pre-remimazolam\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003emPAP (mmHg) post-remimazolam\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePDA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e35\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVSD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e52\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePDA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e23\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eASD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e27\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003emPAP, mean pulmonary artery pressure\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study evaluated the effects of a single intravenous injection of remimazolam on hemodynamic parameters in children with CHD undergoing cardiac catheterization. No significant differences were observed in non-invasive (HR, MAP, CO, CI) or invasive parameters (mSVCP, mRAP, mRVP, mPAP) before and after administration of 0.3 mg\u0026middot;kg⁻\u0026sup1; remimazolam. Additionally, no adverse events, such as bradycardia, hypotension, or hypertension, occurred.\u003c/p\u003e\u003cp\u003eIn this study, a multi-parameter cardiac monitor was used to continuously assess HR and MAP. The changes in HR and MAP before and after administration of remimazolam were compared, and fluctuations remained below 20%, indicating that remimazolam had minimal impact on these parameters. In contrast, Kimoto et al. \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e reported that 75.2% of patients experienced MAP changes\u0026thinsp;\u0026gt;\u0026thinsp;20% from baseline, and 53% exhibited HR changes\u0026thinsp;\u0026gt;\u0026thinsp;20% during general anesthesia.\u003c/p\u003e\u003cp\u003eThe differences between this study and previous findings are likely attributable to variations in methodology. In the present study, remimazolam was administered as a single bolus dose during anesthesia, whereas in studies such as that by Kimoto et al. \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e, the drug was administered continuously via infusion. It is hypothesized that differences in dosing strategy and timing may influence hemodynamic outcomes. Additionally, the accuracy of baseline data in pediatric patients may be affected by agitation or crying prior to anesthesia induction. Nonetheless, the results of this study support the use of a single intravenous injection of remimazolam as a safe and stable option for children undergoing cardiac catheterization and transcatheter closure.\u003c/p\u003e\u003cp\u003eAnesthetic management in children with CHD requires careful medication selection to preserve hemodynamic and electrophysiological stability \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e. In this study, a non-invasive CO monitor was used for continuous CO and CI assessment, offering a minimally invasive approach. No significant changes in CO or CI were observed post-remimazolam administration. Previous studies have supported the hemodynamic stability of remimazolam; Tang et al. \u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e reported reduced fluctuations via stress response modulation and enhanced myocardial contractility, while Qiu et al. \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e noted minimal effects on BP.\u003c/p\u003e\u003cp\u003eBoth non-invasive and invasive hemodynamic parameters were assessed. Following general anesthesia, routine right heart catheterization (femoral vein \u0026rarr; SVC \u0026rarr; RA \u0026rarr; RV \u0026rarr; PA) was performed, and cross-sectional pressures and blood gases were measured. These procedures are standard practice and did not introduce additional trauma. At 3 min after administration of 0.3 mg\u0026middot;kg⁻\u0026sup1; remimazolam, pressures were re-measured. Comparative analysis revealed no significant changes in mSVCP, mRAP, mRVP, or mean PAP. These findings are consistent with the known characteristics of remimazolam, including hemodynamic stability, minimal circulatory fluctuation, mild respiratory depression, and reversibility \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e,\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003ePulmonary hypertension (PH) is a critical indicator in CHD, guiding decisions regarding surgical or interventional treatment and assessing long-term outcomes. As survival rates improve, the prevalence of CHD-related PH is expected to rise \u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. PH is defined as resting mPAP\u0026thinsp;\u0026gt;\u0026thinsp;20 mmHg, as measured by right heart catheterization \u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. In this study, five patients had PH prior to remimazolam administration. No significant change in mPAP was observed post-treatment. Similarly, among patients without PH, mPAP remained stable. These findings indicate that a single dose of remimazolam does not significantly affect mPAP in patients with or without PH.\u003c/p\u003e\u003cp\u003eThis study had limitations. First, it was a single-center study with a limited sample size. Second, only pre- and post-intervention comparisons were conducted without inclusion of comparator drug groups, limiting assessment of remimazolam\u0026rsquo;s advantages over traditional sedatives. Third, the study focused solely on children undergoing catheter-based procedures, excluding those undergoing open-heart surgery. Future studies should involve larger, multicenter cohorts and explore broader CHD populations.\u003c/p\u003e\u003cp\u003eIn conclusion, a single intravenous injection of remimazolam at 0.3 mg\u0026middot;kg⁻\u0026sup1; demonstrates minimal impact on hemodynamics and does not alter mean PAP in children with CHD undergoing cardiac catheterization and transcatheter closure. Remimazolam appears to provide hemodynamic stability and minimal circulatory fluctuation in this patient population.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStudy Design and Patients\u003c/h2\u003e\u003cp\u003eThis study evaluated the effects of a single intravenous injection of remimazolam on the hemodynamic parameter changes in children with CHD. The study was a single-center, prospective, observational, self-controlled study, approved by the Ethics Committee of Shanghai Children's Hospital (2024R059-F01) and registered at the Chinese Clinical Trial Registry (chictr.org.cn; Registration No.: ChiCTR2400084993, Registration Date: May 29, 2024). All procedures were carried out in accordance with the Declaration of Helsinki. Informed consent was obtained from the parents of 40 children with CHD who were scheduled to undergo cardiac catheterization and transcatheter closure. However, due to incomplete data from five patients, only 35 patients were included in the final analysis. The study flow is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eInclusion and Exclusion Criteria\u003c/h3\u003e\n\u003cp\u003eThe inclusion criteria were as follows: age\u0026thinsp;\u0026lt;\u0026thinsp;18 years with American Society of Anesthesiologists (ASA) classification II or III and no premedication. Patients meeting these criteria were scheduled for elective cardiac catheterization and transcatheter closure under general anesthesia.\u003c/p\u003e\u003cp\u003ePatients were excluded if they had a known allergy to benzodiazepines, were taking sedatives or anticonvulsant medications, or had a history of liver or kidney dysfunction or other systemic complications prior to the procedure.\u003c/p\u003e\n\u003ch3\u003eAnesthesia Induction and Maintenance\u003c/h3\u003e\n\u003cp\u003eRoutine intraoperative monitoring was performed using a multi-parameter electrocardiogram monitor (Model AM, Serial No. 6955816; DIVA Laboratories Ltd., Taipei, Taiwan) to assess electrocardiogram, non-invasive blood pressure (BP), and oxygen saturation (SpO₂). Continuous monitoring of cardiac output (CO) and cardiac index (CI) was conducted using a non-invasive CO monitor (Model ICON(C3); Shanghai Meta Care Medical Device Co. Ltd., Shanghai, China).\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eAnesthesia Induction\u003c/h2\u003e\u003cp\u003eAnesthesia was induced intravenously with glycopyrrolate 4 \u0026micro;g/kg (maximum 100 \u0026micro;g), propofol 2\u0026ndash;3 mg/kg, rocuronium 0.6 mg/kg, and sufentanil 0.2 \u0026micro;g/kg. Following induction, a laryngeal mask airway was inserted to facilitate mechanical ventilation.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eAnesthesia Maintenance\u003c/h2\u003e\u003cp\u003eAnesthesia was maintained with pressure-controlled ventilation, targeting an end-tidal CO₂ (EtCO₂) of 35\u0026ndash;45 mmHg. Sevoflurane (2\u0026ndash;3%) was continuously inhaled to maintain a minimum alveolar concentration of 1\u0026ndash;1.3.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eData Measurement and Classifications\u003c/h2\u003e\u003cp\u003eAfter establishing general anesthesia and initiating mechanical ventilation, continuous monitoring of heart rate (HR), BP, SpO₂, CO, and CI was performed. During cardiac catheterization, anesthesiologists recorded invasive hemodynamic parameters including superior vena cava pressure (SVCP), right atrial pressure (RAP), right ventricular pressure (RVP), and pulmonary artery pressure (PAP).\u003c/p\u003e\u003cp\u003eRemimazolam Tosilate for Injection (Jiangsu Hengrui Pharmaceuticals Co., Ltd., Beijing, China; 25 mg/vial; Batch No: 231123AK; National Drug Approval No: H20217078) was administered intravenously at a dose of 0.3 mg/kg. Three minutes after administration, all parameters were re-measured.\u003c/p\u003e\u003cp\u003eThe primary outcome was the change in hemodynamic parameters pre- and post-administration. Secondary outcomes included mean PAP (mPAP) and adverse cardiovascular events, such as bradycardia, hypotension, and hypertension. Bradycardia was defined as HR\u0026thinsp;\u0026le;\u0026thinsp;50 bpm and treated with atropine 0.01 mg/kg IV. Hypotension was defined as a\u0026thinsp;\u0026ge;\u0026thinsp;30% reduction in mean arterial pressure (MAP) from baseline and was confirmed if unresponsive to ephedrine. Hypertension was defined as a\u0026thinsp;\u0026ge;\u0026thinsp;30% increase in MAP from baseline; if unresponsive to deepened anesthesia, it was confirmed. Rescue medications during the peri-anesthetic period included atropine (0.01 mg/kg) and epinephrine (0.01 mg/kg).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eStatistical Analysis\u003c/h2\u003e\u003cp\u003eData were analyzed using SPSS software (version 26.0; IBM Corp., Amonk, NY, USA). Normality was assessed using the Shapiro\u0026ndash;Wilk test. Normally distributed data are presented as meanS\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviationS; non-normally distributed data as medianS (interquartile rangeS) [M (IQR)]. Paired t-tests or Wilcoxon signed-rank tests were used to compare pre- and post-treatment values. A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u0026nbsp;\u003c/strong\u003eThis study was supported by doctors and technicians at the department of cardiology and Department of Imaging, Shanghai Children's Hospital, School of Medicine, Shanghai Jiao Tong University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: Support was provided solely by institutional and departmental sources.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHongyun Li：Write articles\u0026nbsp;，contributions in terms of conception and design, data acquisition and data analysis；\u003c/p\u003e\n\u003cp\u003eXunwei Jiang and Wei Liu\u0026nbsp;：Contributions in surgical operation, measurement of pressure at each cross-section of the heart\u0026nbsp;；\u003c/p\u003e\n\u003cp\u003eJinxia Wang：Application of statistical；\u003c/p\u003e\n\u003cp\u003eYan Jiang：Contributions in design of methodology，Draft articles\u0026nbsp;，\u0026nbsp;make critical revisions to important knowledge-based content；\u003c/p\u003e\n\u003cp\u003eRong Wei：Formulation of overarching research goals，critical review, commentary or revision – including pre-or post publication stages.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e: The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent statement:\u0026nbsp;\u003c/strong\u003eInformed consent was obtained from the parents of 40 children with CHD who were scheduled to undergo cardiac catheterization and transcatheter closure.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical trial number and registry URL:\u0026nbsp;\u003c/strong\u003eChiCTR2400084993, https://www.chictr.org.cn/\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eLee, S. H. et al. Efficacy of Single-Bolus Administration of Remimazolam During Induction of Anesthesia in Patients Undergoing Cardiac Surgery: A Prospective, Single-Center, Randomized Controlled Study. \u003cem\u003eAnesth Analg\u003c/em\u003e \u003cb\u003e139\u003c/b\u003e, 770\u0026ndash;780 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFleck, T. et al. Propofol effect on cerebral oxygenation in children with congenital heart disease. \u003cem\u003ePediatr. Cardiol.\u003c/em\u003e \u003cb\u003e36\u003c/b\u003e, 543\u0026ndash;549 (2015).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eVullo, P. A., Real Navacerrada, M., \u0026Iacute;., I. \u0026amp; Navarro Suay, R. Hemodynamic impact of increasing time between fentanyl and propofol administration during anesthesia induction: a randomised, clinical trial. \u003cem\u003eBraz J. Anesthesiol\u003c/em\u003e. \u003cb\u003e74\u003c/b\u003e, 744230 (2024).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eSpanos, A., Chiu, H. H. \u0026amp; Tye, C. Y. Effects of etomidate given in repeated doses. \u003cem\u003eAnaesth. Intensive Care\u003c/em\u003e. \u003cb\u003e6\u003c/b\u003e, 337\u0026ndash;341 (1978).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKomatsu, R. et al. Anesthetic induction with etomidate, rather than propofol, is associated with increased 30-day mortality and cardiovascular morbidity after noncardiac surgery. \u003cem\u003eAnesth. Analg\u003c/em\u003e. \u003cb\u003e117\u003c/b\u003e, 1329\u0026ndash;1337 (2013).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eHu, B. et al. Comparison of Remimazolam Tosilate and Etomidate on Hemodynamics in Cardiac Surgery: A Randomised Controlled Trial. \u003cem\u003eDrug Des. Devel Ther.\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e, 381\u0026ndash;388 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKilpatrick, G. J. \u0026amp; Remimazolam Non-Clinical and Clinical Profile of a New Sedative/Anesthetic Agent. \u003cem\u003eFront. Pharmacol.\u003c/em\u003e \u003cb\u003e12\u003c/b\u003e, 690875 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKim, K. M. Remimazolam: pharmacological characteristics and clinical applications in anesthesiology. \u003cem\u003eAnesth. Pain Med. (Seoul)\u003c/em\u003e. \u003cb\u003e17\u003c/b\u003e, 1\u0026ndash;11 (2022).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRipoll, J. G. et al. Remimazolam in Cardiac Anesthesia: Analysis of Recent Data. \u003cem\u003eJ. Cardiothorac. Vasc Anesth.\u003c/em\u003e \u003cb\u003e39\u003c/b\u003e, 273\u0026ndash;285 (2025).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eFuruta, M., Ito, H. \u0026amp; Yamazaki, M. Anaesthetic management using remimazolam in a patient with severe aortic stenosis: a case report. \u003cem\u003eBMC Anesthesiol\u003c/em\u003e. \u003cb\u003e21\u003c/b\u003e, 202 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLiu, T. et al. Effect of remimazolam induction on hemodynamics in patients undergoing valve replacement surgery: A randomized, double-blind, controlled trial. \u003cem\u003ePharmacol. Res. Perspect.\u003c/em\u003e \u003cb\u003e9\u003c/b\u003e, e00851 (2021).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNam, S. W. et al. Effects of remimazolam on hemodynamic changes during cardiac ablation for atrial fibrillation under general anesthesia: a propensity-score-matched retrospective cohort study. \u003cem\u003eCan. J. Anaesth.\u003c/em\u003e \u003cb\u003e70\u003c/b\u003e, 1495\u0026ndash;1503 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAoki, Y. et al. 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Anaesth.\u003c/em\u003e \u003cb\u003e131\u003c/b\u003e, 914\u0026ndash;920 (2023).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eNtiloudi, D., Zanos, S., Gatzoulis, M. A., Karvounis, H. \u0026amp; Giannakoulas, G. How to evaluate patients with congenital heart disease-related pulmonary arterial hypertension. \u003cem\u003eExpert Rev. Cardiovasc. Ther.\u003c/em\u003e \u003cb\u003e17\u003c/b\u003e, 11\u0026ndash;18 (2019).\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":"Remimazolam, child, hemodynamics, congenital heart defects, anesthesia","lastPublishedDoi":"10.21203/rs.3.rs-6858449/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6858449/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eMaintaining hemodynamic stability during anesthesia is crucial for patients with congenital heart disease. Remimazolam, a novel benzodiazepine, offers advantages, such as rapid onset, quick recovery, stable hemodynamics, and mild respiratory depression. We aimed to assess the effects of a single intravenous dose of remimazolam on hemodynamics in children with congenital heart disease. Between June and September 2024, 40 children undergoing elective cardiac catheterization and transcatheter closure at Shanghai Children's Hospital were included. Non-invasive (heart rate, blood pressure, oxygen saturation) and invasive hemodynamic parameters (cardiac output, cardiac index, vena cava pressure, right atrial pressure, right ventricular pressure, pulmonary artery pressure) were measured before and after intravenous administration of 0.3 mg/kg remimazolam. Hemodynamic changes were compared pre- and post-treatment. Five patients were excluded due to incomplete data, leaving 35 for analysis (sex, 11 male, 24 female; median age, 6.67 [interquartile range: 4–11.5 years]). No significant changes in non-invasive or invasive hemodynamic parameters were observed after remimazolam administration. Additionally, no adverse effects, such as bradycardia, hypotension, or hypertension, occurred. A single intravenous dose of 0.3 mg/kg remimazolam did not affect hemodynamic parameters in children with congenital heart disease, providing stable hemodynamics with minimal circulatory fluctuations.\u003c/p\u003e","manuscriptTitle":"Effects of remimazolam on hemodynamics in children with congenital heart disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-14 10:27:38","doi":"10.21203/rs.3.rs-6858449/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":"279b2d4e-f3a0-495f-8df3-fc54f56ef764","owner":[],"postedDate":"July 14th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51291829,"name":"Health sciences/Cardiology"},{"id":51291830,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-08-06T06:53:18+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-14 10:27:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6858449","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6858449","identity":"rs-6858449","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}