Perioperative clinical outcomes of remimazolam in regional anesthesia: a systematic review of sedation and safety parameters

Abstract

Background

Regional anesthesia provides significant perioperative benefits, but patients often require sedation for comfort and immobility. Common sedatives such as propofol or dexmedetomidine can cause hemodynamic instability or prolonged recovery. Remimazolam, a newer ultra-short-acting benzodiazepine, has a rapid onset and offset with potentially improved safety. This systematic review aimed to assess the efficacy and safety of remimazolam for sedation during regional anesthesia.

Method

PubMed, Scopus, Web of Science, and Embase were systematically searched up to July 2025 for randomized controlled trials (RCTs) comparing remimazolam with other sedatives (propofol, dexmedetomidine) or placebo during regional anesthesia, including neuraxial techniques (spinal, epidural, combined spinal–epidural) and peripheral nerve blocks. Key outcomes included onset of sedation, depth/quality of sedation, and recovery characteristics, hemodynamic and respiratory events, postoperative nausea and vomiting (PONV), neurocognitive outcomes, and satisfaction. Data were extracted and qualitatively synthesized.

Results

Six RCTs involving 677 patients were included. Remimazolam consistently provided a rapid onset of sedation (about 4–5 min), faster than dexmedetomidine and comparable to propofol. Recovery was also shorter with remimazolam (approximately 7–11 min) compared with both comparators. It provided greater hemodynamic stability, with fewer episodes of bradycardia than dexmedetomidine and less hypotension than propofol. Respiratory safety was favorable, with no serious adverse events and lower risk in some indices compared with dexmedetomidine. The incidence of postoperative nausea and vomiting was low and similar across groups. Remimazolam was not associated with increased delirium or cognitive impairment and in some outcomes showed advantages over propofol. Patient and clinician satisfaction were consistently high.

Conclusion

Remimazolam appears to be an effective and safe sedative option for regional anesthesia, offering a rapid onset and recovery, stable hemodynamics, and minimal respiratory and neurocognitive side effects. Based on the currently limited evidence, it may represent a favorable alternative to traditional sedatives for maintaining patient comfort during regional anesthesia procedures; however, larger, high-quality trials are warranted.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12871-026-03669-3.

Introduction

Regional anesthesia has become an integral part of contemporary anesthesia and surgical procedures, providing several valuable benefits, including decreased exposure to systemic anesthetics, enhanced postoperative analgesia, and reduced incidence of perioperative complications [1–3]. Despite these benefits, adequate sedation is essential in caring for patients during regional anesthesia, specifically to ensure patient comfort, immobility, and anxiety management [4]. The ideal sedative agent should have a rapid onset and recovery, minimal respiratory and cardiovascular depression, and an approved safety profile [5].

Remimazolam, a newly developed ultra-short-acting benzodiazepine, has recently received considerable attention as a rising sedative agent in procedural sedation and general anesthesia [6]. Its rapid metabolism is due to tissue esterases into an inactive metabolite, resulting in predictable pharmacokinetics with a short context-sensitive half-life [7]. In contrast to some established sedatives such as midazolam or propofol, remimazolam has a stable hemodynamic profile with a reduced risk of respiratory depression, making it an appropriate option for vulnerable patients [8, 9].

Although remimazolam has been commonly studied in general anesthesia and procedural sedation, its role in regional anesthesia remains limited and under investigated [10]. In patients undergoing neuraxial or peripheral nerve blocks, the selection and titration of sedatives should be performed to minimize the risk of adverse effects, such as hypotension, respiratory depression, and prolonged recovery [11]. The pharmacological characteristics of remimazolam make it a potentially suitable agent in these settings; however, a complete assessment of its perioperative effects should be conducted in this regard [12].

This systematic review aims to synthesize the current clinical evidence concerning the use of remimazolam in regional anesthesia, with an emphasis on sedation quality and safety parameters, and recovery outcomes.

Method

Study design

This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [13], and the protocol has been registered on the PROSPERO database (Registration ID: CRD420251105364). This review aimed to summarize and analyze the perioperative clinical outcomes of remimazolam in patients undergoing regional anesthesia, with a particular focus on sedation quality and safety-related outcomes.

Data sources and searches

We conducted a comprehensive search without language or date restrictions on July 13, 2025, across four major electronic databases: PubMed, Scopus, Web of Science, and Embase, covering all records from inception to the search date. The search strategy incorporated relevant combinations of keywords related to remimazolam, or regional anesthesia, and sedation.

Representative terms included: “remimazolam”, “remimazolam tosilate”, “spinal anesthesia”, “epidural anesthesia”, “neuraxial anesthesia”, “regional anesthesia”, “sedation”, “procedural sedation”, and “conscious sedation”. The results were imported into EndNote (version 21) for organization and deduplication. The full search strategies for PubMed, Embase, Scopus, and Web of Science are detailed in supplementary file 1.

Eligibility criteria

Inclusion criteria

The inclusion criteria for this systematic review were defined using the PICO framework—Population, Intervention, Comparison, and Outcomes. Studies were included if they met the following criteria: (1) Adult patients (≥ 18 years) undergoing surgery under regional anesthesia, including spinal, epidural, combined spinal–epidural, or peripheral nerve block procedures. (2) Intraoperative administration of remimazolam for procedural sedation. (3) A control group receiving an alternative sedative agent (e.g., propofol, dexmedetomidine) or placebo/no sedation. (4) Reporting at least one sedation-related outcome (including onset time, depth or quality of sedation, and recovery characteristics) or at least one safety-related outcomes, including hemodynamic stability (e.g., hypotension, bradycardia), respiratory safety (e.g., desaturation), PONV, cognitive and neuropsychological effects (e.g., delirium), and satisfaction.

Eligible studies included randomized controlled trials (RCTs) and retrospective comparative studies.

Exclusion criteria

We excluded studies based on the following conditions: [1] non-original publications (e.g., reviews, case reports, letters, conference abstracts) [2], no access to full text despite contacting authors [3], pediatric populations (< 18 years) [4], pregnant women [5], studies conducted under general anesthesia, and [6] studies lacking adequate methodological detail or not reporting sedation- or safety-related outcome.

No restrictions were applied regarding publication date or language. One non-English study (in Chinese) was accurately translated and reviewed.

Study selection

All retrieved records were independently screened by the first author (Ch. R.) and the corresponding author (Kh. K.) based on titles and abstracts. The full texts of potentially eligible studies were then reviewed by all five authors to determine final inclusion according to the predefined eligibility criteria. Any disagreements during the selection process were resolved through discussion until consensus was achieved.

Data extraction

The extracted data from each study included the following items: general study characteristics (such as first author’s name, year of publication, country, and study design), intervention and control groups, type of regional anesthesia used, patient demographics, assessed outcomes, and instruments or scales used for outcome measurement. Outcomes were grouped into predefined domains, including sedation effectiveness, hemodynamic and respiratory safety, postoperative nausea and vomiting (PONV), Cognitive and neuropsychological effects, satisfaction, and other outcomes. In cases of disagreement between reviewers, the final decision was made in consultation with the corresponding author (Kh. K). The forms used for data extraction are presented in Supplementary File 2.

Risk of bias

The Cochrane Risk of Bias 2 (RoB 2) tool was used to assess the methodological quality of the six RCTs included in this review [14]. This tool evaluates five domains: [1] bias arising from the randomization process [2], bias due to deviations from intended interventions [3], bias due to missing outcome data [4], bias in measurement of outcomes, and [5] bias in selection of the reported results. Each domain is rated as having “low risk” (green), “some concerns” (yellow), or “high risk” (red) of bias, and an overall judgment is made accordingly.

Data synthesis

Given the clinical and methodological heterogeneity across the included studies—particularly in terms of intervention protocols, sedation scoring systems, dosage regimens, and outcome definitions—a meta-analysis was deemed inappropriate. Instead, the results were synthesized narratively, focusing on key sedation and safety-related outcomes across comparable subgroups.

Outcomes were organized into predefined domains, and a structured data-charting form was used to support consistency in synthesis. Within each domain, findings were compared qualitatively by examining the direction and consistency of effects across studies, while accounting for differences in populations, types of regional anesthesia, and monitoring tools. All interpretations were made cautiously and were limited to the strength of the available evidence.

Artificial intelligence assistance

We used a large language model (ChatGPT 4.5, OpenAI) to assist with English language editing, grammar correction, paraphrasing, and improving readability. All outputs were carefully reviewed, verified, and edited by the authors to ensure accuracy and adherence to academic standards.

Results

Literature search

Figure 1 shows the process of selecting studies. The initial systematic search identified 124 records. After eliminating 53 duplicate records, 71 studies remained for title and abstract screening. Out of these, 51 studies were excluded due to not meeting eligibility criteria. From the remaining 20 articles, the full texts of them were assessed for eligibility, and finally, six studies met the inclusion criteria and were included in the systematic review.

Fig. 1.

PRISMA 2020 flow diagram of study selection for the current systematic review

Six RCTs, published between 2023 and 2025, were included in this review. Four studies came from China, and two from South Korea.

Study and patient characteristics

The studies evaluated the use of remimazolam as a sedative agent during regional anesthesia, in comparison with propofol [15, 16], dexmedetomidine [4, 17, 18], and saline [19]. A total of six studies included 677 participants, with individual sample sizes ranging from 70 to 238. All participants were adults (aged 18 − 100 years), and both genders were represented. The American Society of Anesthesiologists (ASA) classification was reported in all studies except one [4]. Three studies enrolled participants with ASA class I–III [17–19], one study included those with ASA class I–II [9], and one study included those with ASA class II–III [15]. Different types of regional anesthesia were administered across studies and included spinal [4, 16, 18, 19], epidural [19], combined spinal-epidural [15, 17, 19], peripheral nerve blocks [16, 18], and local infiltration [16]. Surgical procedures mainly included orthopedic, urological, and general surgeries. A detailed summary of each study’s characteristics is presented in Table 1.

Table 1.

Summary of included studies evaluating remimazolam in regional anesthesia

Author, Year, Country	Design	Sample Characteristics	Type of surgery:	Intervention & Control (Dosage/Regimen)	Sedation Outcome Measures	Outcomes Reported	Results summary
Dan Qiao et al. (2025) China	RCT	N = 238 (RMMZ: 160, saline: 78) Age ≥ 65 years Gender: 51% male, 49% female in CON; 46% male and 54% female in INT ASA: I, II, III	Cystoscopy, TURP, hemorrhoidectomy, surgical amputation, TKA, PKR	INT: RMMZ Initial dose: 5.0 mg over 1 min. Maintenance dose: 0.2 mg·kg− 1·h− 1 CON: 0.9% sodium chloride Initial dose: 5 mL of 0.9% saline over 1 min. Maintenance dose: 0.2 mL·kg− 1·h− 1	MOAA/S BIS	cognitive function, POD, sleep, anxiety, postoperative satisfaction, HR, MAP, PONV drowsiness, headache, dizziness, gloss coma, chill, satisfaction	RMMZ achieved a 98.9% sedation success rate in elderly patients under neuraxial anesthesia, while ensuring hemodynamic stability, lowering delirium risk, improving sleep quality, and enhancing patient experience.
Ting-Ting Li et al. (2024) China	RCT	N: 105 (HRMZ: 35, LRMZ: 34, PRO: 36) Age: 18–65 years Gender: HRMZ: 51.4% male, 48.6% female; 52.9% male, LRMZ: 47.1% female; PRO: 55.6% male, 44.4% female ASA: I, II	Elective surgery (Extremities, Pelvic floor and perineum, Thoracic and abdominal walls)	HRMZ; Initial dose: 0.1 mg/kg BW + 0.5 mg/kg/h. Maintenance dose: 0-3 mg/kg/h LRMZ; Initial dose: 0.05 mg/kg BW + 0.5 mg/kg/h. Maintenance dose:0-3 mg/kg/h PRO group Initial dose: 1.0 mg/kg BW+3 mg/kg/h. Maintenance dose: 0-4.5 mg/kg/h	MOAA/S	Anterograde amnesia, injection pain, spontaneous movement during surgery, hypertension, hypotension, desaturation, bradycardia, tachycardia, PONV, POD, satisfaction score	RMMZ suggests rapid, stable, and adequately deep sedation with some anterograde amnesia and no increase in adverse events, supporting its broader clinical use in regional anesthesia.
Sangho Lee et al. (2023) Korea	RCT	N: 78 (39/group) Age: 18–100 years Gender: 53.9% male, 46.1% female (both Groups) ASA: I, II, III		INT: RMMZ Initial dose: 2.5 mg over 1 min. Maintenance dose: 0.1-1 mg/kg/h CON: DEX Initial dose: 1 µg/kg for 10 min.Maintenance dose:0.2–0.7 µg/kg/h	MOAA/S	Ori, Respiratory depression(desaturation), HR, BP, RR, hypotension, hypertension, PONV, POD, AKI	Compared with DEX, RMMZ results in higher ORi 15 min after sedation and a higher intraoperative HR. These properties make it suitable for patients with low baseline SpO₂ or those at risk of bradycardia.
Seung-Wan Hong et al. (2024) Korea	RCT	N: 70 (35/group) Age: 38 ± 12 in DEX Group; 39 ± 15 in RMMZ Group Gender: 20 male, 15 female in DEX Group; 22male, 13female in RMMZ Group	Orthopedic surgery	INT: RMMZ group Initial dose: 6 mL/kg/h (6 mg/kg/h) for 10 min. Maintenance dose: 1 mL/kg/h (1 mg/kg/h) CON: DEX group Initial dose: 6 mL/kg/h (6 µg/kg/h) for 10 min. Maintenance dose: 1 mL/kg/h (1 µg/kg/h)	MOAA/S	HR, MAP, RR, Postoperative pain, PONV	RMMZ demonstrated significantly faster onset and recovery from sedation compared with DEX, with no notable differences in hemodynamic parameters or respiratory depression.
Yufei Chen et al. (2024) China	RCT	N: (80 40/group) Age:40–80 years Gender: 45% male, 55% female in DEX Group; 35%male, 65% female in RMMZ Group ASA: I, II, III	Elective orthopedic surgeries	INT: RMMZ group Initial dose: 0.03 mg/kg/min. Maintenance dose: 0.2–0.5 mg/kg/h CON: DEX group Initial dose: 0.3 µg/kg. Maintenance dose: 0.2–1.0 µg/kg/h	Ramsay score, BIS	SpO2, HR, MAP, RR, Lethargy, satisfaction	RMMZ reached the target sedation level more rapidly than DEX and was characterized by a favorable safety profile, rapid onset and recovery, fewer adverse effects, and higher patient satisfaction while maintaining adequate sedation depth.
DUAN Gongchen et al. (2024) China	RCT	N: 106 (53/group) Age: 65–90 years Gender: 25 male, 28 female in PRO Group; 24 male, 29 female in RMMZ Group ASA: II, III	THA, PFNA	INT: RMMZ Group Initial dose: 0.05 mg/kg over 1 min. Maintenance dose:0.1–0.3 mg·kg− 1·h− 1. CON: PRO Group Initial dose: 0.3–0.5 mg/kg over 1 min. Maintenance dose: 0.5-3 mg·kg− 1·h− 1	BIS and MOAA/S	MAP, HR, RR, SpO2, emergence time, amnesia, POD, DNR, PONV, agitation, use of vasoactive drugs, Blood loss, Urine output	RMMZ provides effective sedation and hemodynamic stability, with minimal impact on early neurocognitive function, and demonstrates superior overall safety compared with PRO.

INT Intervention group, CON Control Group, RMMZ Remimazolam, DEX Dexmedetomidine, PRO Propofol, RCT Randomized Controlled Trial, MOAA/S Modified Observer’s Assessment of Alertness/Sedation Scale, TURP Trans Urethral Resection of the Prostate, TKA Total Knee Arthroplasty, PKR Partial Knee Replacement, PFNA Proximal Femoral Nail Antirotation, THA Total hip arthroplasty, CSEA Combined Spinal-Epidural Anesthesia, Ori Oxygen Reserve Index, LOS length of stay, PACU Postoperative Nausea and Vomiting, AKI acute kidney injury, POD Postoperative Delirium, DNR Delayed Neurocognitive Recovery, RR respiratory rate, HR Heart rate, BP Blood pressure, MAP Mean Arterial Pressure, BIS Bispectral Index, BW kg Body Weight, HRMZ High-dosage Remimazolam group, LRMZ Low‐dosage Remimazolam group

Risk of bias

The methodological quality of the six included RCTs was evaluated using the RoB 2 tool. Two reviewers (Kh. K. and Ch. R.) independently assessed the risk of bias for each included study. Discrepancies were resolved through discussion with a third reviewer (B. N.).

Two studies [4, 17] were judged to have a low risk of bias across all five domains. Three studies [15, 16, 18] raised some concerns, mostly related to randomization or selective outcome reporting. One study [19] was rated as having a high risk of bias, primarily due to deviations from intended interventions and missing outcome data. The evaluation of risk of bias judgments is summarized in Table 2.

Table 2.

Risk of bias assessment for randomized controlled trials using the Cochrane risk of bias 2 tool

Study	D1	D2	D3	D4	D5	Overall Risk
TT. Li et al. (2024)	LR	SC	LR	SC	SC	SC
S. Lee et al. (2023)	SC	LR	LR	LR	SC	SC
SW. Hong et al. (2024)	LR	LR	LR	LR	LR	LR
Y. Chen et al. (2024)	LR	LR	LR	LR	LR	LR
D. Gongchen et al. (2024)	SC	LR	LR	LR	LR	SC
D. Qiao et al. (2025)	LR	HR	HR	LR	SC	HR

D1: Randomization – Bias arising from the randomization process

D2: Deviations – Bias due to deviations from intended interventions

D3: Missing Data – Bias due to missing outcome data

D4: Measurement – Bias in measurement of outcomes

D5: Selection – Bias in the selection of the reported result

Outcomes

Sedation

The Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scale was used in five studies [4, 15, 16, 18, 19], making it the most commonly used tool. Bispectral index (BIS) monitoring was employed in three studies [15, 17, 19], and Ramsay Sedation Scale was used as a complementary metric in one study [17].

The onset time of sedation and achievement of target sedation levels were assessed in four studies [4, 16, 17, 19]. In the study by Hong et al., study the time to reach MOAA/S ≤ 3 was significantly shorter with remimazolam than dexmedetomidine (4 ± 1 min vs. 11 ± 3 min; p < 0.001). Chen et al. also reported a shorter sedation time in the remimazolam group (3.69 ± 0.75 min) compared with dexmedetomidine (9.59 ± 1.03 min; p < 0.0001) [17]. In the study by Li et al., the proportion of patients achieving MOAA/S 1–4 within 3 min was significantly higher in the high-dose remimazolam (HRMZ) group compared with the low-dose (LRMZ) group (85.7% vs. 58.8%; p < 0.001), indicating a dose-dependent onset profile [16]. The propofol group exhibited a similar proportion (82.9%), suggesting a similar onset time between HRMZ and propofol. Qiao et al. also reported a rapid onset, with a mean time of 1.61 min to achieve MOAA/S ≤ 2. These findings consistently demonstrate a faster onset of sedation with remimazolam than dexmedetomidine, and a comparable onset profile to propofol under certain conditions [19].

Sedation quality and depth were reported in two studies [16, 19]. Li et al. showed that patients receiving remimazolam (both HRMZ and LRMZ) spent a greater proportion of time in deeper sedation (MOAA/S 0–2), whereas those in the propofol group spent more time in lighter sedation states (MOAA/S 4–5) [16]. Qiao et al. also reported a high overall sedation success rate (98.93%) with remimazolam [19]. These data suggest that remimazolam may provide both effective and stable sedation within the preferred range.

Sedation recovery time was examined in five studies [4, 15–17, 19]. Qiao et al. reported a mean recovery time (from drug discontinuation to MOAA/S = 5) of 8.03 min [19]. A similar recovery time was reported by Li et al. across all groups (HRMZ, LRMZ, and propofol), with no significant differences (mean: 7.9 ± 5.7 min; p = 0.971) [16]. Hong et al. observed a significantly faster emergence in the remimazolam group compared with dexmedetomidine (11 ± 3 min vs. 16 ± 5 min; p < 0.001) [4]. Similarly, Chen et al. reported that time to wakefulness was significantly shorter in the remimazolam group (7.53 ± 2.28 min) compared with dexmedetomidine (12.74 ± 4.29 min; p < 0.0001) [17]. Furthermore, Gongchen et al. found a significantly faster recovery time in the remimazolam group compared with propofol (p < 0.05) [15]. In general, these findings suggest that remimazolam provides a rapid and predictable recovery profile.

Hemodynamic stability

Hemodynamic parameters during sedation were evaluated in all six studies, primarily heart rate (HR) and blood pressure [4, 15, 16, 18, 19]. Three studies reported that HR remained significantly higher in the remimazolam groups than in the dexmedetomidine group [4, 17, 18]. Chen et al. found significantly lower rates of bradycardia in the remimazolam group (7.5%) compared with dexmedetomidine (52.5%; p = 0.003) [17]. Qiao et al. reported mild reductions in mean arterial pressure (MAP) and HR with remimazolam; however, these values remained within safe limits [19]. Li et al. found incidences of hypotension and bradycardia across all groups (HRMZ, LRMZ, and propofol), with no significant differences between them [16]. Gongchen et al. reported a lower incidence of hypotension and bradycardia in the remimazolam group compared with the propofol group (p < 0.05), although no significant differences were noted in MAP [15]. Overall, remimazolam showed favorable hemodynamic stability in all studies, with a low incidence of hypotension and minimal bradycardic events.

Respiratory safety

All six studies evaluated respiratory function during sedation, including parameters such as respiratory rate (RR), oxygen saturation (SpO₂), and oxygen reserve index (ORi) [4, 15, 16, 18, 19]. Qiao et al. reported a mild decrease in SpO₂ after remimazolam administration, although it remained above 95% without clinical concern [19]. Li et al. reported desaturation events (SpO₂ < 90%) in 5.7% (HRMZ), 2.9% (LRMZ), and 8.6% (propofol), with no significant differences between groups [16]. Lee et al. found comparable rates of respiratory depression between remimazolam (12.8%) and dexmedetomidine (15.4%) groups (p = 1.000), while a greater than 50% reduction in intraoperative ORi was significantly less frequent in the remimazolam group (17.9% vs. 43.6%; p = 0.027) [18]. Chen et al. reported that desaturation was more frequent with remimazolam (5%) than with dexmedetomidine (2.5%); however, all events were transient and clinically manageable [17]. Hong et al. and Chen et al. demonstrated stability in RR in both groups in their studies [4]. Similarly, Gongchen et al. found no significant difference in the incidence of hypoxemia between remimazolam and propofol groups [15]. Overall, remimazolam was associated with a favorable respiratory safety profile, with minimal effect on respiratory rate and oxygenation, and no serious respiratory adverse events were reported across the included studies.

PONV

PONV was assessed in five studies [4, 15, 16, 18, 19]. The findings showed a low incidence, with no significant difference between remimazolam and comparators, including saline, propofol, and dexmedetomidine (p > 0.05).

Cognitive and neuropsychological effects

Delirium was evaluated in four studies [15, 16, 18, 19]. Three studies reported no significant difference in the incidence of postoperative delirium between remimazolam and comparators (p > 0.05) [16, 18, 19]. Conversely, Gongchen et al. reported a lower incidence of delirium, delayed neurocognitive recovery, and verbal memory decline with remimazolam compared with propofol (p < 0.05), while overall cognitive test scores, including Mini-Mental State Examination [MMSE], digit-symbol, and clock-drawing, did not differ significantly between groups (p > 0.05) [15]. Similarly, Qiao et al. found no cognitive impairment based on MMSE and Montreal Cognitive Assessment (MoCA), with no significant differences between groups in perioperative anxiety or sleep quality (p > 0.05) [19].

The outcomes related to memory were mentioned in two studies [15, 16]. Li et al. reported high rates of anterograde amnesia among all groups, with no significant differences between groups (p = 0.650) [16], whereas Gongchen et al. found a higher incidence of intraoperative amnesia in the remimazolam group compared with the propofol group (p < 0.05) [15]. Overall, remimazolam suggests a suitable neurocognitive safety profile.

Satisfaction

Patient satisfaction with sedation was assessed in three studies [16, 17, 19]. Two studies found significantly higher patient satisfaction with remimazolam than with other agents (saline and dexmedetomidine) (p < 0.001) [17, 19]. Researcher satisfaction was significantly higher in the remimazolam group than in the saline group (P < 0.001) [19]. Moreover, Li et al. evaluated anesthesiologist satisfaction and noted higher satisfaction scores among anesthesiologists for remimazolam compared with propofol (p = 0.023), but patient satisfaction was similarly high across groups with no significant difference (p = 0.306) [16]. Anesthesiologist satisfaction was correlated with deeper sedation levels, while patient satisfaction was associated with decreased time spent in lighter sedation.

Other outcomes

No significant differences related to various secondary parameters were reported between groups across five studies including, drowsiness, headache, dizziness, reduced level of consciousness (reported in the original study as ‘gloss coma’) [19]; injection pain and spontaneous movement [16]; PACU stay and acute kidney injury [18]; postoperative pain [4]; and surgical variables such as operative time, blood loss, agitation, urine output, and sufentanil consumption (all p > 0.05) [15]. Notably, Qiao et al. found a significantly lower incidence of chills in the remimazolam group (p < 0.001) [19], and Chen et al. reported a significantly lower incidence of lethargy in the remimazolam group compared with dexmedetomidine (2.5% vs. 17.5%; p = 0.003), and fewer patients experienced multiple adverse events [17].

Discussion

This systematic review synthesized evidence from six RCTs (677 patients) to assess remimazolam as a sedative during regional anesthesia. Across the included studies, remimazolam was generally associated with rapid onset and recovery, acceptable hemodynamic profiles, and a low incidence of respiratory complications. These findings suggest potential advantages, although they should be interpreted with caution given the limited number of studies and variability in study populations and sedation protocols.

Our analysis suggests that remimazolam may attain target sedation levels significantly faster than dexmedetomidine and with an onset profile similar to propofol. These findings are consistent with prior pharmacodynamic studies that report rapid gamma-aminobutyric acid type A (GABA-A) receptor–mediated effects and metabolism via tissue esterases [20, 21]. This rapid onset of action may be advantageous in regional anesthesia, where procedural efficiency is important. In addition, in older adults at increased risk of delayed emergence, remimazolam yielded shorter recovery times than dexmedetomidine and propofol, as demonstrated in randomized trials [15, 17]. Notably, sedation depth was generally maintained within the desired range, reducing intraoperative arousal without prolonging recovery. These findings suggest the potential of remimazolam as a practical sedative, providing a balance between rapid onset, high-quality sedation, and a controllable recovery profile.

Hemodynamic stability was generally more favorable with remimazolam, with lower incidences of bradycardia compared with dexmedetomidine and fewer hypotensive episodes compared with propofol in most studies. These observations are consistent with mechanistic evidence suggesting that remimazolam may produce less sympathetic inhibition relative to α2-adrenergic agonists and propofol [22–24]. Such cardiovascular advantages may hold clinical significance for patients with limited cardiac reserve or those at risk of autonomic instability during neuraxial blockade.

Respiratory safety was generally preserved across the included trials, with no statistically significant differences in the incidence of hypoxic events between remimazolam and comparator agents, and no reported cases of severe respiratory compromise were reported. Compared with propofol and dexmedetomidine, remimazolam was reported to maintained stable respiratory rates and oxygenation, consistent with evidence from systematic reviews indicating that respiratory depression with remimazolam in procedural sedation is unusual, typically transient, and occurs less frequently than with traditional sedatives [25, 26]. This respiratory profile may be beneficial for high-risk populations, such as the elderly or individuals with preexisting respiratory conditions.

PONV occurred at low rates across all studies, with no significant differences between remimazolam and comparator agents such as propofol or dexmedetomidine. Existing studies report low and comparable rates of PONV across groups, suggesting that remimazolam does not increase the risk of this complication; however, the current evidence is not sufficient to establish whether it reduces PONV. These findings are consistent with evidence from other systematic reviews and meta-analyses. For example, a comprehensive meta-analysis reported that remimazolam was associated with a reduced risk of PONV compared with volatile anesthetic agents [27], while another study found no significant difference in its incidence compared with propofol [28]. Moreover, other studies have indicated that remimazolam is similar to dexmedetomidine in terms of the incidence of PONV [12]. Collectively, current evidence indicates the suitability of remimazolam as an alternative to propofol and dexmedetomidine, combining benefits such as enhanced hemodynamic stability and reduced injection site pain [26], without increasing PONV risk. This represents an important clinical consideration for patients at high risk of cardiovascular instability and PONV.

Neurocognitive outcomes were generally favorable, with no increase in postoperative delirium or cognitive decline compared with control agents. One study [15] reported a possible reduction in delayed neurocognitive recovery and verbal memory impairment compared to propofol, consistent with preclinical findings indicating that benzodiazepine-based sedation may confer reduced neurotoxicity relative to non-γ-aminobutyric acid (GABA)-ergic agents [29]. The occurrence of anterograde amnesia with remimazolam was similar to or slightly greater than that reported with propofol, which may enhance intraoperative comfort without clear evidence of adverse effects on postoperative cognition.

Satisfaction measures, although inconsistently reported, tended to favor remimazolam, particularly when compared with saline or dexmedetomidine. Higher anesthesiologist satisfaction appeared to relate to more stable sedation depth, whereas patient satisfaction was more commonly associated with rapid recovery and minimal intraoperative awareness. These subjective outcomes, although secondary, remain important indicators of the overall quality of anesthesia care [30].

The results of this systematic review suggest that remimazolam may have potential clinical utility as a sedative during regional anesthesia. Its consistently rapid onset and recovery, combined with a lower reported incidence of bradycardia compared with dexmedetomidine and fewer hypotensive episodes than propofol in the available studies, indicate that remimazolam could be a suitable option in settings where hemodynamic stability and prompt sedation are priorities. Nonetheless, dexmedetomidine remains valuable owing to its sedative and mild analgesic properties [31], although propofol remains a well-established sedative [32]. The selection of these agents should be individualized to consider patient-specific factors, the surgical context, and potential risks. Future research should address the identified limitations, including the need for larger, multicenter RCTs to validate these findings. Besides that, direct comparative studies in specific populations, such as the elderly or patients with cardiovascular or respiratory conditions, would improve evidence-based clinical decision-making.

This systematic review was conducted rigorously in accordance with established guidelines and based on a comprehensive search strategy. Nonetheless, several limitations remain, reflecting both the nature of the included studies and the review methodology. First, a key limitation is the small number of eligible studies, reflecting the relatively recent introduction of remimazolam as an anesthetic agent and the resulting scarcity of clinical research in the context of regional anesthesia. Consequently, our findings have limited generalizability, and the limited evidence base precluded a robust quantitative synthesis (meta-analysis). Although our search strategy allowed for comparative observational studies, none met the eligibility criteria due to insufficient comparators or outcome reporting. Therefore, only RCTs were ultimately included, reflecting the limited availability of suitable observational evidence on remimazolam in regional anesthesia. Second, heterogeneity in outcome definitions limited comparability. For example, the definitions for “respiratory depression” differed across studies, with some using SpO₂ thresholds < 90%, others relying on RR, and one study employing the oxygen reserve index (ORi) as the primary criterion [18]. Additionally, most trials used the MOAA/S scale [4, 16, 18], while some also utilized BIS monitoring [15, 19], and one study reported the Ramsay Sedation Scale alongside BIS [17]. The inconsistency in assessment tools made direct comparisons of sedation challenging depth. Third, the patient populations across the studies were not homogeneous. Two of the studies [17, 19] specifically focused on elderly patients (with mean ages > 65 years), whereas others included general age groups. Fourth, all included studies were conducted in Korea and China. This geographical concentration may limit the generalizability of the findings to more diverse populations with different healthcare protocols, genetic backgrounds, and treatment practices. Fifth, while two studies involving pregnant women met the inclusion criteria, these studies were excluded due to the distinct physiological alterations during pregnancy, which can change the pharmacodynamics and pharmacokinetics of remimazolam, thereby limiting comparability with the general population [33, 34].

These methodological limitations highlight the necessity of future research, which should include multicenter RCTs employing standardized outcome definitions to enhance comparability across studies. Additionally, further evidence is required to clarify optimal dosing strategies for remimazolam in various surgical contexts, its safety and efficacy in high-risk and elderly populations, and its interaction with other perioperative medications. Notably, populations not represented in this review, such as pregnant women, warrant dedicated investigation due to their unique physiological characteristics.

Conclusion

In conclusion, this systematic review summarizes the current evidence on remimazolam as a sedative agent in regional anesthesia. The available trials suggest that remimazolam may provide effective intraoperative sedation with a generally favorable safety profile, characterized by rapid onset and recovery, and adequate maintenance of sedation. Hemodynamic stability was frequently reported as a potential advantage, particularly in patients with cardiovascular comorbidities. Furthermore, several studies indicated encouraging respiratory and neurocognitive outcomes, as well as a relatively low incidence of PONV. However, these findings should be interpreted with caution, given the limited number of studies, varying sample sizes, and heterogeneity across trials. While remimazolam shows promise as an alternative to traditional sedatives such as propofol and dexmedetomidine, further large-scale, high-quality, multicenter trials are warranted to confirm its efficacy and safety across diverse surgical populations.

Abbreviations

PRISMA

Preferred Reporting Items for Systematic Reviews and Meta-Analyses

PROSPERO

International Prospective Register of Systematic Reviews

PICO

Population, Intervention, Comparison, and Outcomes

RCTs

Randomized Controlled Trials

PONV

Postoperative Nausea and Vomiting

RoB

Risk of Bias

P

P-value

ASA

American Society of Anesthesiologists

MOAA/S

The Modified Observer’s Assessment of Alertness/Sedation scale

BIS

Bispectral index

HRMZ

High-dose Remimazolam

LRMZ

Low-dose Remimazolam

HR

Heart Rate

BP

Blood Pressure

MAP

Mean Arterial Pressure

RR

Respiratory Rate

SpO₂

Oxygen Saturation

Ori

Oxygen Reserve Index

MMSE

Mini-Mental State Examination

MoCA

Montreal Cognitive Assessment

PACU

Post-Anesthesia Care Unit

GABA-A

Gamma-Aminobutyric Acid type A

Authors’ contributions

K.K. and Ch.R. designed the study. K.K., Ch.R., and N.B. performed title/abstract screening. K.K. and Ch.R. extracted data, and assessed the risk of bias; discrepancies were resolved with N.B. K.K. drafted the manuscript. Ch.R. and N.B. contributed to critical revision of the text. P.M. performed literature search and prepared figures. K.K., Ch.R., N.B., and P.M. contributed to data synthesis and analysis. M.M. contributed to literature search support, reference organization, and academic language editing. All authors read and approved the final manuscript.

Funding

This study received no financial support.

Data availability

All data generated during this research are included in this published article and in the supplementary information file.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.