Comparison of remimazolam and midazolam for sedation during colonoscopy in Japanese patients: A propensity score matching analysis.

Objectives: To compare the efficacy and safety of sedation with midazolam and remimazolam for colorectal endoscopy. Methods: This single-center, two-arm, post-hoc analysis of the REM-IICTJP01 study investigated the efficacy and safety of remimazolam for gastrointestinal endoscopic sedation. We enrolled 40 and 208 patients who underwent colonoscopy under remimazolam and midazolam sedation, respectively, during the same period. The primary outcome was the time from the end of the colonoscopy until discharge. The secondary outcomes included the time from the end of the colonoscopy until awakening, dosage, and adverse events. Propensity score matching was employed to eliminate the effect of confounding factors. Results: Thirty-seven patients in each group were matched. After propensity matching, the time to awakening after colonoscopy was 28.0 (13.0-37.0) min in the midazolam group and 0 (0-0) min in the remimazolam group; moreover, the time till discharge was 40.0 (35.0-46.5) min in the midazolam group and 0 (0-5.0) min in the remimazolam group, both of which were significantly shorter in the remimazolam group (p < 0.01). The number of additional doses was 0 (0-0) and 2 (1-3) in the midazolam and remimazolam groups, respectively. The total dose was 2.0 (2.0-3.5) and 6.0 (5.0-7.0) mg in the midazolam and remimazolam groups, respectively. Conclusions: Remimazolam yielded significantly faster times to awakening and discharge safely compared to midazolam.

Comparison of hypotension between propofol and remimazolam-propofol combinations sedation for day-surgery hysteroscopy: a prospective, randomized, controlled trial.

BACKGROUND: A combination of remimazolam and propofol could produce more stable sedation. A good medication regimen should consider not only efficacy but also safety, especially hypotension. The aim of the current study was to compare the incidence and amount of hypotension by propofol versus remimazolam-propofol combinations in day-surgery hysteroscopy. METHODS: Patients were randomly assigned to receive either propofol (Group P, n = 125) or remimazolam-propofol combinations (Group RP, n = 125) at a 1:1 ratio. Intravenous injection of sufentanil 0.1ug/kg were administered before sedative medication. In group P, a bolus of 2.5 mg/kg propofol was administered. In group RP, intravenous anesthesia was commenced with 0.125 mg/kg remimazolam and 1 mg/kg propofol. After loss of consciousness, propofol was maintained at 6 mg/kg/h. The primary outcomes were the incidence and amount of hypotension during surgery. Hypotension was defined as a MAP less than 65mmHg for at least 1 min. The amount of hypotension was assessed by time-weighted average intraoperative MAP under a threshold of 65 mmHg. The secondary outcomes were various anesthesia related parameters and some adverse events. RESULTS: In group P, 25 patients (20.0%) experienced hypotension during hysteroscopy compared with 9 patients (7.2%) in group RP, for a difference of 12.8% (RR 2.778, 95%CI [1.352-5.709]). The combination of remimazolam and propofol resulted in significantly lower TWA (Time Weighted Average) threshold 0.14 (0.10-0.56) mmHg in group RP compared to 0.31 (0.15-0.67) mmHg in group P. The total dose of propofol was nearly double in group P compared to group RP. A significantly higher frequency of injection pain and low oxygen saturation was observed in the group P than that of the group RP. Hiccup was observed only in group RP. The incidences of body movement, bradycardia and vomiting were no significant difference between groups. CONCLUSION: The incidence and amount of hypotension by remimazolam-propofol combinations was significantly less than that by propofol sedation in day-surgery hysteroscopy. The optimization of medication regimen would attenuate the harm of hypotension and contribute to patients' rapid recovery in day surgery. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2400079888 (date: 15/01/2024).

Comparison of remimazolam and midazolam for preventing intraoperative nausea and vomiting during cesarean section under spinal anesthesia: a randomized controlled trial.

Background: Preventing intraoperative nausea and vomiting (IONV) is crucial for maternal safety during cesarean section under spinal anesthesia. While midazolam is known to prevent IONV, we hypothesized that remimazolam would be superior due to its minimal hemodynamic effects. We compared the effects of the two drugs on IONV. Methods: Parturients scheduled for cesarean section were randomly assigned to receive either midazolam or remimazolam. They received midazolam 2 mg or remimazolam 5 mg, with additional doses administered upon request. The primary outcome measure was the incidence of newly developed IONV during sedation. Other outcomes included overall IONV, rescue antiemetic use, shivering, hemodynamic variables, sedation scale scores, and satisfaction scores. Results: Data from 80 participants were analyzed. Deeper sedation was induced in the remimazolam group (PGroup × Time < 0.001) despite comparable hemodynamic trends between the groups. The incidence of overall IONV was comparable between the two groups (27.5% in the midazolam group vs. 17.5% in the remimazolam group, absolute risk reduction [ARR]: 0.100, 95% confidence interval [CI] [-0.082, 0.282], P = 0.284); however, newly developed IONV during sedation was significantly reduced in the remimazolam group (20.0% vs. 5.0%, ARR: 0.150, 95% CI [0.009, 0.291], P = 0.043). The need for rescue antiemetics was also lower in the remimazolam group (15.0% vs. 2.5%, ARR: 0.125, 95% CI [0.004, 0.246], P = 0.048). Conclusion: Remimazolam significantly reduced the incidence and severity of newly developed IONV compared with midazolam, with minimal impact on hemodynamics, making it a useful sedative option for cesarean section.

Comparison of Remimazolam and Propofol in Recovery of Elderly Outpatients Undergoing Gastrointestinal Endoscopy: A Randomized, Non-Inferiority Trial.

Purpose: We designed this trial to compare the recovery time of remimazolam and propofol in elderly patients undergoing painless gastrointestinal endoscopy. Patients and Methods: In this randomized, non-Inferiority trial, 360 patients aged 65 years or older, scheduled for elective outpatient gastrointestinal endoscopy, were randomly assigned to the remimazolam combined with fentanyl (RF) group or the propofol combined with fentanyl (PF) group. The primary outcome was the post-anesthesia care unit (PACU) stay time, defined as the time from the end of the examination to scoring 9 points using the Modified Post-Anesthetic Discharge Scoring System (MPADSS) criteria. Secondary outcomes included sedation-related adverse events, recall, injection pain, as well as postoperative Quality of Recovery-15 (QoR-15) scores and Pittsburgh Sleep Quality Index (PSQI) scores at 1 day, 1 week, and 1 month postoperatively. Results: A total of 351 patients completed the study, with 174 receiving remimazolam and 177 receiving propofol. The PACU stay time in RF group was non-inferior to that in PF group [14 (11, 18) vs 13 (10, 17), mean difference 1 (95% confidence interval 0, 2), P=0.084 for noninferiority]. However, remimazolam was associated with lower rate of hypoxemia [4.7% (8/180) vs 12.4% (22/180), P=0.011], reduced use of vasoactive drugs [1 (0, 1) vs 1 (1, 2), P<0.001], less injection pain [2 (1.2%) vs 35 (21.3%), P<0.001], and lower recall [20 (11.8%) vs 36 (20.3%), P=0.034]. There were no differences in the QoR-15 scores and PSQI scores at postoperative 1 day, 1 week, and 1 month between groups. Conclusion: This non-inferiority study revealed that in elderly outpatients undergoing gastrointestinal endoscopy, remimazolam achieved recovery times comparable to propofol, with fewer associated complications.

Remimazolam Anesthesia for a Pediatric Patient With Glutaric Aciduria Type I: A Case Report.

Glutaric aciduria type I (GA-1) is a rare metabolic disorder caused by an autosomal, recessive, inherited deficiency of glutaryl-CoA dehydrogenase. Reports on the anesthetic management of patients with GA-1 are limited. It has been suggested that inhalation anesthesia is safer than propofol due to the mitochondrial dysfunction inherent in GA-1. However, inhalation anesthesia poses a risk, albeit rare, of malignant hyperthermia, which can result in severe neurological damage in GA-1 patients. Therefore, we considered that management using remimazolam might be effective and, provided a successful general anesthesia using it for a pediatric patient with GA-1. We report a case of a four-year-old girl with GA-1 who underwent a laparoscopic gastrostomy under general anesthesia. Remimazolam was used for both induction and maintenance of anesthesia. Our perioperative management also included measures to prevent a hypercatabolic condition such as adequate hydration and blood glucose control. The patient had an uneventful perioperative course and was discharged on postoperative day 7. Thus, remimazolam is proposed as a new option for anesthetic management in patients with GA-1. Additionally, tailored perioperative management that addresses the unique characteristics of GA-1 is crucial for favorable outcomes.

Triple Anesthesia: Combining Sevoflurane, Propofol, and Remimazolam for General Anesthesia in a Case Series.

There is an ongoing quest for an ideal uniform anesthesia regimen that adequately covers all nociceptive stimuli preventing hypertension and tachycardia while minimizing hypotension and the need for antihypotensive drugs. Recently, the ultra-short-acting benzodiazepine remimazolam was approved for the induction and maintenance of general anesthesia. Combining remimazolam with sevoflurane and propofol may combine the antiemetic properties of propofol, the depressing (immobilizing) effect on spinal motor neurons of sevoflurane, and the hemodynamic stability afforded by remimazolam, making it an attractive addition to the armamentarium of anesthetic agents. We describe five patients in whom general anesthesia was maintained with this triple combination, along with multimodal analgesia. All patients maintained hemodynamic stability at sufficient hypnotic depth, with no observable movement during surgery or episodes of cardiac arrhythmias.

Remimazolam in intensive care unit: Potential applications and considerations.

This manuscript explores the potential use of Remimazolam in the intensive care unit (ICU) and critical care units, considering its pharmacological characteristics, clinical applications, advantages, and comparative effectiveness over current sedatives and anesthetics. We reviewed existing PubMed and Google Scholar literature to find relevant studies on Remimazolam in ICU. We created search criteria using a combination of free text words, including Remimazolam, critical care, intensive care, sedation, anesthesia, pharmacokinetics, and pharmacodynamics. Relevant articles published in the English language were analyzed and incorporated. Remimazolam is an ultra-short-acting benzodiazepine derivative promising for sedation and anesthesia. It is a safer option for hemodynamically unstable, elderly, or liver or kidney issues. It also has comparable deep sedation properties to propofol in the ICU. Furthermore, it reduces post-procedural delirium and patient comfort and reduces the need for additional sedatives in pediatric patients. In conclusion, Remimazolam is an excellent alternative to current sedatives and anesthetics in the ICU. Its cost is comparable to that of current medications. Further research on its long-term safety in the ICU and its broader application and incorporation into routine use is necessary.

Remimazolam in Cardiac Anesthesia: Analysis of Recent Data.

Interest in remimazolam has surged in recent years, thanks to its advantageous pharmacologic profile. This ultra-short-acting benzodiazepine is noted for its rapid onset and termination of action, organ-independent elimination, availability of a reversal agent, and excellent hemodynamic stability. Although the use of remimazolam has been explored in various anesthesia settings and procedures, data on its application in cardiovascular anesthesia and catheterization laboratory procedures remain limited. This review evaluates the latest literature to assess remimazolam's role in cardiovascular anesthesia across different settings and procedures. The analysis shows that remimazolam offers anesthesia without significant hemodynamic instability and a reduced need for vasopressors, with an incidence of perioperative adverse events comparable to that of other agents. These findings are relevant for both the induction and maintenance of general anesthesia in catheterization laboratory procedures and general anesthesia in elective cardiac surgery. Although further research is needed to fully understand remimazolam's role in cardiovascular anesthesia, its favorable hemodynamic and safety profile suggests that it is a promising option for cardiac anesthesiologists in both the catheterization laboratory and the operating room.

Incidences of Rocuronium Use during Anesthetic Induction in Adult Patients Undergoing Orthopedic Surgery Using Supraglottic Airway Devices: A Retrospective Analysis.

Background/Objectives: Neuromuscular blocking agents (NMBAs) are not usually necessary during the induction of general anesthesia in patients using supraglottic airway (SGA) devices. In this study, we assessed the incidences of rocuronium use in adult patients undergoing general anesthesia using SGA devices. Methods: From September 2022 to August 2023, the medical records of adult patients (≥19 years) who underwent orthopedic surgery using SGA devices were retrospectively investigated. The incidences of rocuronium use during anesthetic induction were analyzed according to the anesthetic induction drug. The association of rocuronium use during anesthesia was analyzed in terms of demographic (age, sex, height, and weight), surgical (surgical time), and anesthetic factors (premedication, anesthetic agent, anesthetic time). Results: In total, 321 patients were enrolled. The incidence rate of rocuronium use during anesthetic induction was 28.3%. In the subgroup analysis, patients receiving total intravenous anesthesia (TIVA) with propofol (PPF) and remifentanil showed a markedly lower incidence (14.4%) than the other anesthetic groups. Premedication or short anesthetic duration was associated with lower incidences of rocuronium use. Demographic and other anesthetic factors did not seem to affect the incidences of rocuronium use during anesthesia. Conclusions: The incidence of rocuronium use during anesthetic induction with SGA devices was significantly lower with the PPF-TIVA compared to that using remimazolam-TIVA or inhalational anesthesia. Premedication with midazolam and shorter operation times were associated with a significantly lower incidence of rocuronium use.

Remimazolam ameliorates postoperative cognitive dysfunction after deep hypothermic circulatory arrest through HMGB1-TLR4-NF-κB pathway.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a complication of deep hypothermic circulatory arrest (DHCA). Various amounts of neurologic dysfunctions have been shown after DHCA, which has often been attributed to systemic inflammatory response syndrome and cerebral ischemia/reperfusion injury. Remimazolam is one of the commonly used anesthetic drugs with protective actions against inflammatory diseases, such as sepsis and cerebral ischemia/reperfusion injury. Here, we determined the protective effect and potential mechanism of action of remimazolam against neuronal damage after DHCA. METHODS: A rat model of DHCA was established, and a gradient dosage of remimazolam was administered during cardiopulmonary bypass (CPB). The cognitive function of rats was evaluated by Morris water maze. Hematoxylin and eosin and TUNEL staining were performed to assess hippocampus tissue injury and neuronal apoptosis. Inflammatory cytokines concentration were analyzed by enzyme-linked immunosorbent assay. The protein expression was analyzed using automated electrophoresis western analysis and immunohistochemical analysis. RESULTS: The appropriate dosage of remimazolam reduced histologic injury, neuronal apoptosis, microglia activation, and secondary inflammatory cascades, as well as the downregulation of the expression of the HMGB1-TLR4-NF-κB pathway after DHCA, improved the memory and learning abilities in DHCA rats. Further, administration of a TLR4 antagonist TAK-242 had a similar effect to remimazolam, while the TLR4 agonist LPS attenuated the effect of remimazolam. CONCLUSIONS: Remimazolam could ameliorate POCD after DHCA through the HMGB1-TLR4-NF-κB signaling pathway.

A Retrospective Comparative Study of the Frequency of Hypotension in Pediatric Cardiac Catheterization under General Anesthesia: Remimazolam versus Sevoflurane.

OBJECTIVE: To compare the incidence of hypotension between remimazolam and sevoflurane under general anesthesia for cardiac catheterization in patients with congenital heart disease. DESIGN: Retrospective observational study. SETTING: A single university hospital with 300 pediatric cardiac catheterizations by general anesthesia performed annually. PARTICIPANTS: Patients younger than 15 years who underwent cardiac catheterization under general anesthesia between March 1, 2021, and December 31, 2022. Exclusion criteria were general anesthesia maintained with other than remimazolam or sevoflurane, receipt of remifentanil, American Society of Anesthesiologists score 4 or 5, emergency procedures, and no direct arterial pressure measurement. INTERVENTIONS: General anesthesia was maintained with remimazolam or sevoflurane. MEASUREMENTS AND MAIN RESULTS: A total of 309 patients were analyzed, including 28 in the remimazolam group and 281 in the sevoflurane group. Propensity score matching adjusted for confounding factors resulted in 28 patients in each arm, with no apparent differences in background factors. Hypotension was defined as a time-averaged area > 1, in which systolic arterial pressure fell below 80% of the baseline from the start of anesthesia to the end of procedure. The significance level was set at P < .05. The incidence of hypotension was 39.3% in the remimazolam arm and 46.4% in the sevoflurane arm, with no significant difference (P = .79), although the ratio of the median systolic arterial pressure to the baseline value was significantly higher in the remimazolam arm (91.4 ± 15.2% vs 83.2 ± 11.4% in the sevoflurane arm; P = .03). CONCLUSIONS: Remimazolam was not associated with a lower incidence of hypotension compared to sevoflurane during pediatric cardiac catheterization for congenital heart disease while maintaining significantly higher blood pressure overall.

Toward Model-Informed Precision Dosing for Remimazolam: A Population Pharmacokinetic-Pharmacodynamic Analysis.

Remimazolam, widely used for procedural sedation and general anesthesia, is a new ultra short-acting benzodiazepine for intravenous sedation and anesthesia. We aim to characterize the pharmacokinetics/pharmacodynamics (PK/PD) of remimazolam and its metabolite CNS 7054 in healthy Chinese volunteers using population analysis and suggest an optimal dosing regimen for sedation therapy. Data were collected from a single-center, placebo-controlled, randomized, and dose-escalation clinical pharmacology study. Forty-six healthy volunteers received a single infusion dose of remimazolam, while nine healthy subjects received a continuous infusion of remimazolam. A population PK/PD model was established and RxODE and Shiny in R were used to design the remimazolam dosing regimens. A three-compartment model best described the PK of remimazolam and a two-compartment model with one transit compartment was adopted for CNS 7054. The relationship between exposure and the bispectral index was best described using an effect compartment model with an inhibitory sigmoid model. Additionally, a web-based dashboard was developed to provide individualized dosing regimens, complemented by a graphical illustration of the PK/PD profiles of the proposed dosing regimen. The established population PK/PD model characterized the dose-exposure-response relationship of remimazolam well, which could be applied to optimize individual dosing regimens.

Remimazolam attenuates lipopolysaccharide-induced neuroinflammation and cognitive dysfunction.

OBJECTIVE: Remimazolam, a novel benzodiazepine, is widely used as an anesthetic in endoscopic procedures; however, its effects on cognitive function remain unclear, limiting its broader application in general anaesthesia. Neuroinflammation is a well-established key factor in the etiology and progression of cognitive dysfunction, including conditions such as Alzheimer's disease, Parkinson's disease, postoperative delirium, and postoperative cognitive dysfunction. Preclinical studies have demonstrated that remimazolam exerts anti-inflammatory and neuroprotective effects, and clinical reports indicate a reduced incidence of postoperative delirium in patients treated with remimazolam. Nevertheless, whether remimazolam improves cognitive function through its anti-inflammatory properties remains uncertain. This study aimed to investigate the neuroprotective effects of remimazolam and its underlying mechanism in a lipopolysaccharide (LPS)-induced model of neuroinflammation, neuronal injury, and cognitive dysfunction METHODS: C57BL/6 J male mice were administered LPS intraperitoneally to establish a model of neuroinflammation-induced cognitive impairment. A subset of mice received remimazolam via intraperitoneal injection 30 minutes prior to LPS administration. Cognitive performance was evaluated using behavioural tests, including the Morris Water Maze (MWM), Novel Object Recognition (NOR) test, and Open Field Test (OFT). Hippocampal tissues were analyzed by haematoxylin-eosin (HE) staining to assess structural changes. Inflammatory markers, including Interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α, were quantified using enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR. Immunofluorescence was used to detect translocator protein (TSPO) and markers of microglia activation (IBA-1, CD16/32, and CD206). RESULTS: (1) Remimazolam reversed LPS-induced cognitive deficits, as evidenced by shorter spatial exploration latency and increased platform crossings in the MWM, and an elevated recognition index in the NOR test. (2) Remimazolam improved hippocampal morphology, reducing LPS-induced neuronal damage. (3) Remimazolam significantly decreased levels of hippocampal inflammatory cytokines, inhibited microglial activation, promoted M2-type microglia polarization, and increased TSPO expression. CONCLUSION: Remimazolam demonstrated neuroprotective and anti-neuroinflammatory effects in a mouse model of LPS-induced cognitive impairment. These effects are likely mediated through the regulation of TSPO, which inhibits microglial activation and promotes the polarization of microglia from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype.

Comparing subjective quality of recovery between remimazolam- and propofol-based total intravenous anesthesia for surgical procedures: a meta-analysis.

BACKGROUND: Remimazolam is a novel ultra-short-acting benzodiazepine that has been recently introduced as an alternative to propofol for general anesthesia. While both agents have been compared in terms of safety and efficacy, their relative effects on postoperative quality of recovery (QoR) remain unclear. Therefore, this meta-analysis aimed to compare the effects of remimazolam and propofol on subjective QoR in surgical patients who underwent general anesthesia. METHODS: Medline, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched from inception to May 28, 2024 to identify randomized controlled trials comparing remimazolam and propofol in terms of postoperative QoR. The Cochrane risk-of-bias tool (RoB 2) was used to assess study quality. QoR score on postoperative day (POD) 1 (primary outcome), QoR scores on PODs 2-3, QoR dimensions, time to loss of consciousness, other recovery characteristics, and rescue analgesia requirement were evaluated using random-effects meta-analyses. RESULTS: This meta-analysis included 13 studies published between 2022 and 2024 involving 1,418 patients. QoR was evaluated using either the QoR-15 (10 studies) or QoR-40 (3 studies) questionnaire. The pooled results indicated no significant difference in the QoR scores on POD 1 (standardized mean difference: 0.02, 95% confidence interval [CI]: - 0.20, 0.23, P = 0.88, I2 = 73%) and PODs 2-3 between remimazolam and propofol. Furthermore, no significant differences were observed in QoR dimensions, length of postanesthesia care unit (PACU) stay, and time to extubation as well as in the risks of agitation and postoperative nausea and vomiting. Patients administered remimazolam exhibited slower anesthetic induction (mean difference (MD): 32.27 s) but faster recovery of consciousness (MD: - 1.60 min) than those administered propofol. Moreover, remimazolam was associated with a lower risk of rescue analgesia requirement in the PACU (risk ratio: 0.62, 95% CI: 0.43, 0.89, P = 0.009, I2 = 0%) but not in the ward. CONCLUSION: Remimazolam is a potential alternative to propofol for general anesthesia as it offers similar QoR to the latter and has advantages in terms of consciousness recovery and immediate postoperative analgesia requirement.

Neonatal anesthesia with remimazolam Reduces the expression of synaptic proteins and increases depressive behavior in adult mice.

The demand for pediatric anesthesia has risen in decades, raising concerns about the neurotoxic potential of anesthetics like remimazolam, which may impact neurodevelopment and later cognitive function. This study utilized a neonatal mouse model to assess remimazolam's neurodevelopmental effects. Results indicate that remimazolam-exposed mice displayed cognitive impairment and depressive behaviors in adulthood. Acute reductions in synaptic protein expression post-anesthesia were observed, along with long-term decreases in hippocampal choline acetyltransferase levels, reduced dendritic spine density in the CA1 region, and microglial proliferation. Collectively, these findings suggest that remimazolam can induce neurotoxicity and neuroinflammation, leading to synaptic dysfunction and associated cognitive and behavioral deficits.

Remimazolam Use in Cardiac Anesthesia: A Narrative Review.

Remimazolam, a novel ultra-short-acting intravenous benzodiazepine, has garnered recent attention for its use as a general anesthetic. This narrative review aims to summarize and analyze the available literature on the effects of remimazolam use in cardiac surgical patients, including its effects on hemodynamics, safety in patients with baseline myocardial dysfunction, and impact on postoperative management including time to emergence and extubation. Finally, there is discussion regarding potential drawbacks of adopting remimazolam as a routine anesthetic for cardiac surgery.

[Remimazolam-Update on basic pharmacologic principles and clinical potential]. / Remimazolam ­ Update zu Grundlagen und klinischem Potenzial.

In recent years the still relatively new short-acting benzodiazepine remimazolam has been approved and clinically implemented in several countries and regions. Remimazolam is also now approved in the EU and the market launch in Germany is expected in the not too distant future. This is therefore a good point in time to summarize the current evidence for various areas of application, including general anesthesia, sedation and intensive care medicine as well as different dosing schemes.

The effects of remimazolam in combination with estazolam on postoperative hemodynamics and pain intensity in patients undergoing laparoscopic gastrointestinal surgery.

OBJECTIVE: This study aimed to investigate the effects of combining remimazolam with estazolam on hemodynamics and pain levels after laparoscopic gastrointestinal surgery. METHODS: A total of 184 patients who underwent laparoscopic gastrointestinal surgery were enrolled in this double-blind randomized controlled trial. The patients were divided into four groups: Study Group 1(Remimazolam), Study Group 2(Estazolam), Study Group 3(Remimazolam + Estazolam), and Control Group. Anesthesia induction included intravenous injection of remimazolam and estazolam in the study groups, while the control group received normal saline. Hemodynamic parameters, stress responses, anxiety levels, and pain intensity were assessed at various time points. RESULTS: The results showed that the combination of remimazolam and estazolam significantly improved hemodynamic parameters compared to the control group. Study Group 3 exhibited the lowest anxiety levels and stress responses among all groups. Furthermore, Study Group 3 had the lowest pain intensity scores at different postoperative time points. CONCLUSION: The combination of remimazolam and estazolam effectively stabilized hemodynamics, reduced anxiety levels, and alleviated pain intensity after laparoscopic gastrointestinal surgery. These findings suggest that this combination therapy has the potential to improve surgical outcomes and patient comfort.