Wang QW, Wu L, Wang ZQ, Zhang J, Bai SC. Clinical application of remimazolam benzenesulfonate in elderly patients undergoing laparoscopic cholecystectomy under intravenous general anesthesia. World J Gastrointest Surg 2026; 18(7): 121776 [DOI: 10.4240/wjgs.v18.i7.121776]
Corresponding Author of This Article
Shuan-Cheng Bai, Full Professor, Affiliated Baotou Clinical College of Inner Mongolia Medical University, No. 61 Huancheng Road, Donghe District, Baotou 014040, Inner Mongolia Autonomous Region, China. 13947236426@163.com
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Wang QW, Wu L, Wang ZQ, Zhang J, Bai SC. Clinical application of remimazolam benzenesulfonate in elderly patients undergoing laparoscopic cholecystectomy under intravenous general anesthesia. World J Gastrointest Surg 2026; 18(7): 121776 [DOI: 10.4240/wjgs.v18.i7.121776]
Qi-Wei Wang, Shuan-Cheng Bai, Affiliated Baotou Clinical College of Inner Mongolia Medical University, Baotou 014040, Inner Mongolia Autonomous Region, China
Lan Wu, Affiliated Inner Mongolia Clinical College of Inner Mongolia Medical University, Hohehot 010017, Inner Mongolia Autonomous Region, China
Zhi-Qiang Wang, Jia Zhang, Department of Anesthesiology, Baotou Central Hospital, Baotou 014040, Inner Mongolia Autonomous Region, China
Author contributions: Wang QW and Wu L conceived the study; Wang ZQ and Zhang J conducted the methodology and investigation, prepared the original draft of the manuscript, and performed the statistical analysis; Bai SC contributed to the review and editing of the manuscript.
Supported by Public Hospital Research Joint Fund Science and Technology Project, No. 2023GLLH0236.
Institutional review board statement: The study was approved by the Ethics Committee of Baotou Central Hospital [Approval No. KYLL2024(Ethics)082].
Clinical trial registration statement: This study is registered at https://www.chictr.org.cn/index.html. The registration identification number is ChiCTR2600117283.
Informed consent statement: All participants provided written informed consent. The study was conducted in accordance with the Declaration of Helsinki.
Conflict-of-interest statement: The authors declare no competing interests.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement: All patient data can be requested by sending an email to the corresponding author.
Corresponding author: Shuan-Cheng Bai, Full Professor, Affiliated Baotou Clinical College of Inner Mongolia Medical University, No. 61 Huancheng Road, Donghe District, Baotou 014040, Inner Mongolia Autonomous Region, China. 13947236426@163.com
Received: April 1, 2026 Revised: April 13, 2026 Accepted: May 14, 2026 Published online: July 27, 2026 Processing time: 117 Days and 19.3 Hours
Abstract
BACKGROUND
Elderly patients undergoing laparoscopic cholecystectomy (LC) are more vulnerable to hemodynamic instability and anesthesia-related adverse events. Remimazolam benzenesulfonate may be a useful alternative to propofol, but comparative evidence remains limited.
AIM
To compare the efficacy and safety of remimazolam benzenesulfonate and propofol in elderly patients undergoing LC.
METHODS
A total of 120 elderly patients scheduled for LC were randomized based on random number table and opaque sealed envelopes into 2 groups (n = 60 each): A propofol control group (CG) and a remimazolam benzenesulfonate observation group (OG). Anesthesia induction was intravenous propofol (1.5 mg/kg) or remimazolam benzenesulfonate (0.2 mg/kg), and rocuronium bromide (0.6 mg/kg) and sufentanil (0.4 ug/kg) in both groups. Anesthesia maintenance included targeted intravenous infusion of the assigned sedatives with remifentanil; intermittent rocuronium was used to keep a train-of-four ratio of ≤ 0.2. The primary outcome was mean arterial pressure (MAP). Secondary outcomes: Oxygen saturation, heart rate (HR), Bispectral index (BIS), perioperative use of vasoactive drugs, Riker Sedation-Agitation Scale (RSAS), Visual Analogue Scale (VAS), Mini Mental State Examination (MMSE), and incidence of adverse reactions.
RESULTS
After applying the predefined inclusion and exclusion criteria, 59 patients in both groups completed the trial. Relative to the CG, the OG had a longer induction time and delayed attainment of BIS < 60 (P < 0.05). However, the OG was found to have more stable MAP and HR throughout the perioperative period, lower consumption of vasoactive agents, and fewer adverse events (P < 0.05). Post-extubation RSAS scores were also lower in the OG (P < 0.05). Postoperatively, the OG had greater MMSE scores at 6 hours and lower VAS pain scores at 1 hour and 6 hours (P < 0.05). No significant variances between groups were revealed at other time points.
CONCLUSION
Relative to propofol, remimazolam benzenesulfonate has more stable hemodynamics and a lower incidence of adverse reactions during total intravenous anesthesia in elderly patients undergoing LC. While remimazolam showed benefits in early postoperative recovery, cognitive function, and pain control, these benefits were lost over time.
Core Tip: This study demonstrates that remimazolam benzenesulfonate offers more stable hemodynamics and a lower incidence of adverse reactions compared to propofol during total intravenous anesthesia in elderly patients undergoing laparoscopic cholecystectomy. Additionally, remimazolam provides benefits in early postoperative recovery, cognitive function, and pain control, though these advantages diminish over time. These findings suggest that remimazolam may be a promising alternative for anesthesia management in this patient population.
Citation: Wang QW, Wu L, Wang ZQ, Zhang J, Bai SC. Clinical application of remimazolam benzenesulfonate in elderly patients undergoing laparoscopic cholecystectomy under intravenous general anesthesia. World J Gastrointest Surg 2026; 18(7): 121776
Globally, the aging population has become a more prominent issue, presenting a significant social and healthcare challenge for many countries[1]. At the same time, the number of people with age-related conditions, including noncommunicable diseases such as metabolic and digestive disorders, is increasing, which puts a significant strain on healthcare systems[2]. Epidemiological studies show that gallbladder diseases, such as gallstones and cholecystitis, are becoming more common in elderly patients, and therefore, the number of elderly patients undergoing anesthesia is increasing[3]. However, because of the age-related decreases in organ function and decreased physiological reserve, elderly patients tend to have a poor tolerance to anesthesia and are more prone to hemodynamic instability during general anesthesia[4]. In addition, the presence of one or more comorbidities has added to anesthesia-related risks in this population. Therefore, careful selection of surgical approaches, anesthesia techniques, and anesthetic agents are necessary to ensure patient safety during anesthesia and surgery.
Laparoscopic cholecystectomy (LC) being a minimally invasive surgical technique, it has quickly become the most favored surgery for symptomatic gallbladder diseases, because of its obvious benefits: Small incisions, decreased postoperative pain, minimal tissue trauma, faster recovery and shorter hospital stays. As a result, LC is now widely used in clinical practice[5,6]. However, LC has high demands on anesthetic management. Anesthesia must not only offer effective analgesia and amnesia for the duration of the procedure, but also enable rapid induction, rapid emergence and high safety profile. Therefore, the choice of a rational, safe and effective anesthetic regimen in elderly patients has become a crucial area of research in modern clinical anesthesiology.
Propofol, as a common intravenous anesthetic agent, has the benefits of fast onset, short duration of action, and high-quality emergence, and has become a common choice for the induction and maintenance of general anesthesia[7]. However, propofol has marked circulatory and respiratory depressant effects and may also cause injection pain, which together limit its use in elderly patients[8,9]. In contrast, remimazolam is a novel benzodiazepine sedative with rapid metabolism, a favorable safety profile, and a low risk of accumulation, making it a potentially useful alternative for elderly patients, in whom hemodynamic stability and recovery quality are particularly important[10-12]. Although its safety and efficacy have been reported in clinical surgery, direct comparative evidence between remimazolam benzenesulfonate and propofol in elderly patients undergoing LC remains limited, especially regarding induction characteristics, intraoperative hemodynamic stability, recovery quality, postoperative cognitive function, and perioperative adverse events[13-15]. Therefore, this randomized controlled trial was designed to compare the anesthetic efficacy and safety of remimazolam benzenesulfonate and propofol in elderly patients undergoing LC under total intravenous anesthesia, with the aim of providing clinical evidence for anesthetic selection in this population.
MATERIALS AND METHODS
Sample size calculation
The key outcome of this research was mean arterial pressure (MAP) under surgical anesthesia in elderly patients. The number of patients was determined by a preliminary pilot study, which showed a MAP of 85.6 ± 7.2 mmHg in the remimazolam benzenesulfonate group and 72.3 ± 9.5 mmHg in the propofol group. Sample size estimation was performed using PASS 16.0 software with a two-sided level of significance (α) of 0.05 and a power (1 - β) of 0.90. The calculation showed that 48 subjects per group were needed, a total of 96 subjects. Accounting for an expected 20% drop out rate, the final enrollment goal was 120 participants, with 60 patients per group.
Patient population
This study enrolled 120 elderly patients who were planned to undergo LC at the Baotou Central Hospital, Inner Mongolia Autonomous Region, China, in the period between September 2024 and November 2025. The patients were randomly assigned to the control group (CG; propofol group, n = 60) or the observation group (OG; remimazolam group, n = 60) with the help of a random number table. The protocol of the research was accepted by the Ethics Committee of Baotou Central Hospital [Approval No. KYLL2024(Ethics)082], and all the participants signed the written informed consent before enrolling in the study.
Patient recruitment
Inclusion criteria: (1) Ages 60 years and older[16]; (2) Surgical indication and fitness to undergo general anesthesia; (3) American Society of Anesthesiologists physical status I-III; (4) Body mass index (BMI): 18.5-30 kg/m2; and (5) Willing to participate in the study, signed informed consent.
Exclusion criteria: (1) Severe cardiac, cerebral, pulmonary, hepatic, renal, or metabolic disease; (2) History of abnormal recovery following previous surgical anesthesia; (3) Acute respiratory tract infection within the last 2 weeks which has not subsided; (4) Persons with neuromuscular disorders, psychiatric illnesses, or severe coagulation disorders; or (5) Persons with known allergy to study medications.
Withdrawal criteria: (1) Surgical cancellation; (2) Change in surgical procedure during the operation; (3) Unplanned postoperative intensive care unit transfer; or (4) Absence of clinical or follow-up data.
Randomization and blinding
Patients were randomly allocated to the propofol or remimazolam group using a random number table. The random sequence was produced by an independent research assistant and kept in opaque sealed envelopes. On the day of surgery, the anesthesiologist opened the envelope before the patient entered the operating room to assure allocation concealment. Patients were allocated to their respective groups according to the predetermined sequence, and they were unaware of their group allocation prior to surgery. Due to the different nature of the anesthetic drugs, the anesthesiologist could not be blinded. Postoperatively, all patient outcome data were collected by an independent data collector who was not involved in anesthesia administration.
Anesthesia methods
All patients were fasting and had fluid restriction pre-operatively. Upon arrival to the operating room, intravenous access was initiated, and mask oxygen therapy was started. Vital signs, such as electrocardiogram, heart rate (HR), MAP, oxygen saturation (SpO2), and Bispectral index (BIS) were continuously monitored. Nerve stimulation electrodes were placed on the ulnar nerve and hooked up to a neuromuscular blockade monitor to measure the baseline train-of-four (TOF) ratio as a reference. During induction, patients in the CG were given intravenous propofol emulsion (Jiangsu Yingke Bio-Pharmaceutical Co., Ltd., H20223914, 20 mL: 0.2 g) at a dose of 1.5 mg/kg. Patients in the OG were treated with intravenous remimazolam benzenesulfonate (Yichang Renfu Pharmaceutical Co., Ltd., H20200006, 25 mg/vial) at a dose of 0.2 mg/kg. Both groups were injected with sufentanil citrate (Yichang Renfu Pharmaceutical Co., Ltd., H20054171, 0.4 μg/kg) and rocuronium bromide (Emeishan Tonghui Pharmaceutical Co., Ltd., H20183305, 0.6 mg/kg) at the same time. BIS and TOF ratios were constantly monitored and tracheal intubation was done if BIS was below 60 and TOF ratio ≤ 0.1. During maintenance, the CG was given infusion of propofol at 2-4 mg/(kg/hour), while the OG was given infusion of remimazolam at the corresponding therapeutic dose. Both groups were injected with remifentanil hydrochloride (Yichang Renfu Pharmaceutical Co., Ltd., H20030197, 0.1-0.3 μg/kg/minute) to keep the anesthesia depth within a BIS value of 40-60. TOF ratios were continuously monitored and additional rocuronium (0.1-0.2 mg/kg) was given intermittently to keep TOF ≤ 0.2 as required by surgery. At the end of surgery, a muscle relaxant antagonist was used: Neostigmine methylsulfate injection (Hefei Yifan Biopharmaceutical Co., Ltd., H20249339, 2 mg) combined with atropine sulfate injection (Hubei Xinghua Pharmaceutical Co., Ltd., H20237122, 1 mg) in the ratio of 2:1, slow intravenous injection. Extubation criteria were TOF ratio of ≥ 0.9, responsiveness to verbal commands, spontaneous respiratory rate of 12-20 breaths/minute, tidal volume of ≥ 5 mL/kg, restoration of cough and swallowing reflexes, and SpO2 of ≥ 95% on room air. Patients were transferred to the recovery room after extubation. Patient-controlled intravenous analgesia (PCIA) was started if the Visual Analogue Scale (VAS) score > 4. The regimen was 0.15 μg/kg sufentanil and 2.5 mg droperidol (Shandong Hualu Pharmaceutical Co., Ltd., H37022102) diluted to 100 mL in 0.9% sodium chloride. The background infusion rate was 2 mL/hour with a bolus dose of 2 mL and a 15 minutes lockout period. During recovery, TOF ratios were rechecked every 15 minutes until patients were fully awake and TOF ≥ 0.9.
Observation indicators
Outcome measures: Primary outcome MAP during surgical anesthesia in elderly patients.
Secondary outcomes: (1) Induction and emergence parameters: Time to loss of eyelash reflex on induction. Sedation emergence time: Defined as the time between the start of the self-terminating anesthetic infusion and the time when the patient is able to open her or his eyes on command. To prevent interference from neuromuscular blockade, emergence was only confirmed and timed if the TOF ratio was ≥ 0.9. Endotracheal tube removal time: Defined as the time from discontinuation of anesthetic and sedative infusion until the patient has TOF ≥ 0.9, is conscious, meets clinical criteria for extubation, and has the tracheal tube removed; (2) Vital signs and anesthesia depth: HR, BIS and SpO2 were measured at the following time points: Pre-anesthesia (T0), intubation (T1), pneumoperitoneum establishment (T2), 30 minutes after surgery (T3) and extubation (T4). Intraoperative administration of vasoactive drugs was also recorded; (3) Adverse events: Assessed events included induction injection pain, bradycardia, hypotension, prolonged recovery from anesthesia (recovery time > 30 minutes), post-extubation respiratory depression, hypoxemia, postoperative nausea, vomiting, dizziness, headache, agitation, somnolence and delirium. Adverse events related to residual neuromuscular blockade (e.g., respiratory depression or limitations of mobility due to the effects of muscle relaxants) were specifically excluded; (4) Sedation-agitation assessment: Assessed at 1 minute (T5), 15 minutes (T6), and 30 minutes (T7) after extubation using the Riker Sedation-Agitation Scale (RSAS). TOF ratio ≥ 0.9 was confirmed before the assessment to prevent interference from residual muscle relaxation. RSAS scoring (1-7 points): (a) Minimal or no response to stimuli, cannot follow commands or communicate; (b) Responds to physical stimuli, incapable of communication or following commands; (c) Drowsy, aroused by gentle shaking or verbal stimulation, able to follow simple commands; (d) Quiet, easily aroused, able to follow commands; (e) Attempts to turn or sit up, calms with verbal reassurance; (f) Requires protective restraints and constant verbal reassurance to limit agitation; and (g) Pulls at endotracheal tube, tries to remove catheters, climbs bed rails, or attacks staff; requires physical restraint RSAS ≥ 5 was considered suggestive of agitation[17]; (5) Cognitive function assessment: Mini Mental State Examination (MMSE) was done 24 hours before the surgery and at 6 hours and 24 hours after the surgery. Postoperative evaluations were only performed after TOF ratio ≥ 0.9 and full reversal of sedation (RSAS = 4). Total MMSE score: 30 points; the higher the score the better the cognitive function[18]; and (6) Pain assessment: Evaluated by the VAS at 1 hour, 6 hours and 24 hours post-operatively. Prior to assessment, TOF ratio of ≥ 0.9 and minimal residual sedation (RSAS = 3-4) were confirmed. VAS scoring (0-10): 0 = no pain; 1-3 = mild pain; 4-6 = moderate pain; 7-10 = severe pain. Higher scores represent greater intensity of pain[19].
Statistical analysis
Data was analyzed by utilizing the statistical software of version 27.0 of the SPSS. The Kolmogorov-Smirnov test was utilized to test the continuous variables’ normality. Continuous data that have a normal distribution are expressed as mean ± SD. For within-group comparisons over multiple time points, repeated measures analysis of variance (ANOVA) was used, and if the assumption of sphericity was satisfied, the standard F-test was used, whereas the Greenhouse-Geisser correction was utilized when the assumption of sphericity was not satisfied. Between-group comparisons were carried out by one-way ANOVA, followed by pairwise comparisons by LSD t-tests. Continuous data with no normal distribution are reported as median (interquartile range), and Kruskal-Wallis H test was utilized for between-group comparisons. Categorical data are presented as n (%) and between-group comparisons were carried out utilizing the Fisher’s exact test or χ2 test, as suitable. A P value < 0.05 was regarded as statistically significant.
RESULTS
During the trial, one patient in the CG was excluded due to difficult extubation requiring intensive care unit admission and one patient in the remimazolam group was excluded due to intraoperative addition of partial hepatectomy. In the end, 118 patients completed the study, with 59 patients in each group. The screening process of the patient is shown in Figure 1.
Comparison of general patient characteristics between the two groups
Comparisons of general characteristics, such as age, gender and BMI, between the two patient groups showed no significant differences (P > 0.05), which indicated that the two groups were similar. The results can be seen in Table 1.
Table 1 Comparison of general characteristics between two patient groups (n = 59), mean ± SD/n (%).
Comparison of anesthetic induction and recovery outcomes between two patient groups
The time to loss of the eyelash reflex and time for BIS to decrease to 60 were significantly longer in the OG than in the CG (P < 0.001). Nevertheless, no significant differences were revealed between the two groups with respect to time to awakening or time to extubation (P > 0.05). The findings are represented in Table 2.
Table 2 Comparison of anesthetic induction and recovery outcomes between two patient groups (n = 59), mean ± SD.
Comparison of hemodynamic parameters between the two groups of patients
Comparison of hemodynamic parameters revealed no significant differences between the groups with respect to HR (F = 2.140, P = 0.149) or SpO2 (F = 0.261, P = 0.611). However, significant group effects were found for (MAP, F = 81.925, P < 0.001) and (BIS, F = 69.713, P < 0.001). All four parameters showed significant time effects (P < 0.001). Moreover, significant group × time interactions existed for HR, MAP, and BIS (P < 0.001) which suggested differences in the temporal changes of these measures between groups, but no significant interaction was found for SpO2 (F = 0.890, P = 0.471) which suggested a similar temporal trend in both groups. Pairwise comparisons showed that the OG had higher HR, MAP and BIS values than the CG at T1-T3 (P < 0.05) but no intergroup differences were found at T0 and T4 (P > 0.05). Within-group analyses revealed that HR and MAP decreased at T1-T3 compared with T0 (P < 0.05), and returned to near baseline at T4. BIS values decreased significantly from T0 to T1-T4 in both groups (P < 0.05), whereas SpO2 increased at T1-T4 compared with T0 (P < 0.05), with no differences between groups. These results are shown in Figure 2.
Figure 2 Comparison of hemodynamic parameters between the 2 groups of patients.
A: Heart rate in beats per minute; B: Mean arterial pressure in mmHg; C: Oxygen saturation in %; D: Bispectral index. aP < 0.05 within the group relative to pre-anesthesia; bP < 0.05 within the group relative to immediately after extubation. T0: Pre-anesthesia; T1: Immediately after intubation; T2: At the time of pneumoperitoneum; T3: 30 minutes after the start of surgery; T4: Immediately after extubation. HR: Heart rate; bpm: Beats per minute; MAP: Mean arterial pressure; SOP2: Oxygen saturation; BIS: Bispectral index.
Comparison of adverse reactions between the 2 groups of patients
The incidence of injection-related induction pain, bradycardia, hypotension and overall adverse events was substantially lower in the OG than in the CG (P < 0.05). No significant differences were revealed between two groups for other adverse events (P > 0.05). The findings are given in Table 3.
Table 3 Comparison of adverse reaction incidence between two patient groups, n (%).
Comparison of vasoactive drug use between two patient groups
The number of patients needing dopamine, norepinephrine, and anisodamine hydrobromide was substantially less in the OG when compared with the CG (P < 0.05). No significant differences were revealed between the groups with respect to use of nitroglycerin (P > 0.05). The results are provided in Table 4.
Table 4 Comparison of medication use between two patient groups, n (%).
Comparison of RSAS and MMSE scores between the two groups of patients
A significant group effect was found for the RSAS scores (F = 97.274, P < 0.001), but neither a significant time effect nor group × time interaction was found. This suggests that the initial difference between the 2 groups was maintained during the observation period and the RSAS score in the OG was consistently better than those in the CG at T5, T6 and T7 (P < 0.05). For MMSE scores, no significant group effect or group and time interaction was found; however, a significant time effect was found (F = 13.852, P < 0.001). The OG had higher MMSE scores than the CG only at 6 hours postoperatively (P < 0.05), and no significant differences were noted at other time points. Within-group analyses found significant changes in MMSE scores over time in both groups, suggesting that time is a crucial factor in the postoperative cognitive function. The findings are represented in Figure 3.
Figure 3 Comparison of Riker Sedation-Agitation Scale and Mini Mental State Examination Scores between the 2 groups of patients.
A: Riker Sedation-Agitation Scale Score; B: Mini Mental State Examination Score. aP < 0.05 within the group relative to 24 hours before surgery; bP < 0.05 within the group relative to 6 hours after surgery. RSAS: Riker Sedation-Agitation Scale Score; MMSE: Mini Mental State Examination Score.
Comparison of VAS scores between the 2 groups of patients
In both subgroups (patients receiving PCIA and those not receiving PCIA), significant group effects, time effects and group × time interaction effects were found in VAS scores (P < 0.001). Pairwise comparisons revealed that VAS scores in the OG were substantially lower than those in the CG at 1 hour and 6 hours after surgery (P < 0.05), although there was no statistically significant difference between the two groups at 24 hours after surgery (P > 0.05). Within-group analyses showed significant differences between time points only in the OG (P < 0.05), but no significant differences were revealed between time points in the CG (P > 0.05). The results are shown in Table 5.
Table 5 Comparison of Visual Analogue Scale scores between 2 patient groups, mean ± SD.
With increasing age, elderly patients have a lower tolerance to anesthesia because of factors such as deterioration of organ function, changes in pharmacokinetics, and increased burden of comorbidities[20], making them more prone to perioperative complications. Although LC is regarded as a minimally invasive procedure, the process of establishing a pneumoperitoneum can have an adverse effect on cardiopulmonary function[21]. In addition, routine preoperative fasting and fluid restriction may lead to relative or absolute hypovolemia. Intraoperative stimuli such as gallbladder traction may further trigger marked variations in vital signs, including HR and blood pressure, during the peri-anesthetic period[22], thus increasing both surgical and anesthetic risks. Therefore, during anesthesia for LC, the anesthetic technique, drug selection and dosing should be individualized based upon the patient’s baseline condition to effectively attenuate perioperative stress responses, maintain hemodynamic stability and minimize postoperative complications.
Our results suggest that remimazolam was associated with a slightly slower onset during anesthesia induction than propofol, whereas no significant differences were observed in recovery time or extubation time. These results are consistent with several meta-analyses[23-25]. A comprehensive review of previous studies suggests that the relatively slower onset of remimazolam may be related to its lower equilibrium rate constant in the effect-site compartment, which delays the attainment of effective anesthetic concentrations in the brain[26]. As to emergence from anesthesia, there is still some controversy and inconsistency in the literature. For example, several phase III clinical trials in Japan and China have shown longer times to emergence and extubation in the remimazolam group than in the propofol group[27]. In contrast, other studies and systematic reviews indicate that these differences might not be clinically significant[28]. These discrepancies can be explained by differences in pharmacokinetic profiles and study designs. When given at low doses and for brief periods of time, the metabolic differences between remimazolam and propofol are minimal. However, during long anesthesia, the high lipid solubility of propofol can cause accumulation in peripheral tissues and thus cause a long recovery time. In contrast, remimazolam is quickly metabolized by tissue esterases, has little dependence on hepatic and renal function and has a low potential for accumulation[11,12].
Regarding postoperative recovery and quality, studies by Duan et al[29] and Park et al[30] showed that remimazolam was related to better postoperative RSAS and MMSE scores than propofol, which is consistent with the results of the present study. This may be attributed to the sedative mechanism of remimazolam through the γ-aminobutyric acid type A receptor, resulting in the ability to precisely titrate and to have excellent controllability. As a result, patients can be kept more consistently in an optimal depth of sedation, decreasing RSAS scores. In addition, remimazolam is quickly hydrolyzed by tissue esterases in vivo and this reaction is independent of hepatic and renal function. Its metabolites do not have sedative activity and thus allow for rapid clearance[31]. These pharmacological properties may be responsible for improved postoperative recovery and overall quality of recovery in elderly patients. Furthermore, Doi et al[32] reported that at similar levels of sedation, remimazolam resulted in higher BIS values than propofol, which is consistent with our findings. Similarly, a randomized controlled trial showed that BIS values changed little with increasing doses of remimazolam, with trough values usually between 50 and 60[33]. One possible reason for this phenomenon is that the relationship between remimazolam and BIS may be affected by the electromyographic activity, such that there is a less pronounced dose-response relationship compared with propofol.
Hemodynamic stability is an important issue in the anesthetic management of elderly patients. The results of this study showed that remimazolam was linked to smaller changes in MAP and HR at the time points T1-T4, as well as a significantly reduced need for vasoactive drugs. In addition, the incidence of bradycardia and hypotension during the induction period was lower than the incidence observed with propofol. These findings are in line with other studies that suggest remimazolam offers better cardiovascular stability[34]. Unlike propofol, which is well known to cause peripheral vasodilation and myocardial depression, remimazolam appears to have less direct cardiovascular depressant effect. Consequently, it may provide a better safety profile of anesthesia in elderly patients. Injection pain is a typical side effect of propofol. In this study, the injection pain’s incidence in the OG (remimazolam group) was substantially lower than that in the CG (propofol group), as in previous reports[31]. This difference may be attributed to the water-soluble formulation of remimazolam, which does not require a lipid emulsion, as well as it is possible to reduce peripheral nociceptive signal transmission by inhibiting the bradykinin pathway[35]. Reducing injection pain not only allows for better patient comfort but may also help reduce the stress response during anesthesia induction.
Regarding postoperative pain, this study found that whether the PCIA was used or not, the VAS scores of the OG were lower than those of the CG at 1 hour and 6 hours after surgery, but there was no statistically significant difference between the two groups at 24 hours. These results may indicate that remimazolam has a better short-term synergistic analgesic effect than propofol in the early postoperative period. However, both propofol and remimazolam are sedatives and lack intrinsic analgesic properties. The phenomenon we observed may be attributable to the finding that remimazolam has been shown to potentiate the effect of remifentanil[36]. Additionally, VAS assessment is by nature subjective. In elderly patients, slower drug metabolism and incomplete recovery of cognitive function in the early postoperative period, as well as stress responses such as anxiety, may play a role in variability of VAS scores.
This study has a number of limitations. First, it is a single-center study that was carried out in one region with a relatively small sample size, which may limit the findings’ generalizability to other regions or healthcare settings. Second, because anesthetic administration requires familiarity with the drugs used, it is difficult for anesthesiologists to implement blinding during anesthesia, and this may introduce a degree of bias. In addition, the observation period was relatively short and follow-up was mainly done in the early postoperative stage; therefore, long-term outcomes and possible complications were not systematically assessed. In clinical practice, anesthetic decisions should be based on individual patient conditions. Future multicenter studies with longer follow-up periods and larger sample sizes are needed to further validate and refine the conclusions of this study.
CONCLUSION
Compared with propofol, remimazolam benzenesulfonate offers more hemodynamic stability and a lower incidence of adverse reactions during total intravenous anesthesia for LC in elderly patients. However, in terms of the quality of postoperative recovery, the cognitive function, and the pain control, remimazolam only shows its advantages in the early postoperative period, which gradually disappears with time. In summary, in elderly patients who undergo LC and have limited hemodynamic tolerance and need to improve circulatory stability, remimazolam benzenesulfonate might be a more appropriate choice for intravenous anesthesia.
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