Introduction

Anaesthesia procedures are essential for dental treatments. However, patients with high anxiety, dental phobia, needle phobia, resistance to local anaesthetics and cognitive disabilities may not be suitable candidates for local, conventional1 or computerised anaesthesia.2 In these cases, sedation techniques are necessary.

Midazolam, a commonly used benzodiazepine, is frequently employed for procedural sedation in dental practice. Although it effectively manages anxiety and discomfort during dental procedures, it has several drawbacks and risks.3 One key limitation is its tendency to accumulate in the body, especially in patients with renal or hepatic failure, or when given in repeated doses. This can lead to prolonged sedation and extended drug effects, potentially affecting post-procedure activities requiring attention and coordination.4

Midazolam may induce respiratory depression, especially at high doses or when combined with other central nervous system depressants.5 This risk is heightened in patients with pre-existing respiratory conditions or in the older population, who may already have compromised pulmonary function and take other medications that potentiate these effects, such as opioids or psychotropic drugs, thereby increasing the risk of complications.6 Additionally, midazolam interacts with the cytochrome P450 enzyme system, potentially affecting the metabolism of other drugs and leading to altered efficacy or safety profiles.7

In March 2023, the European Medicines Agency (EMA) approved remimazolam besylate (Byfavo 20 mg) for procedural sedation.8 Remimazolam offers pharmacokinetic and pharmacodynamic advantages over midazolam, including a shorter half-life and faster onset, enabling more precise sedation control and quicker cognitive recovery.9 It accumulates less in the body, reducing risks of prolonged sedation and respiratory impairment.10,11 Remimazolam's predictable and adjustable sedative effect also allows for tailored sedation levels, minimising the chances of over- or under-sedation.12,13

Remimazolam has shown a favourable safety profile in clinical trials, with minimal severe side effects. However, studies in dentistry remain limited, primarily conducted in China,4,9,14,15 Korea,16 Japan17 and the United States.18 Further research is needed to explore its benefits for anxious or odontophobic patients, individuals with cognitive disabilities, those with a strong gag reflex, patients needing stress reduction, and for lengthy or invasive dental procedures.

This prospective cohort study aimed to assess the success rate of intravenous conscious sedation in dental treatments using remimazolam besylate. It evaluated pre-operative anxiety, sedation depth, psychomotor and physiological recovery, and variation in vital parameters. The study also assessed anaesthesiologist intervention rates, amnesia prevalence, adverse effects and subjective anxiolytic outcomes. To the best of our knowledge, this represents the first European clinical study on remimazolam besylate for intravenous conscious sedation in dentistry.

Materials and methods

Design

This single-centre, non-profit, prospective cohort pharmacological observational study was approved by the local ethics committee (Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Territorial Ethics Committee Lombardy 3) (Trial ID 4996) and adhered to the principles of the Helsinki Declaration (June 1964, amended by the 75th World Medical Association General Assembly held in Helsinki, Finland, from October 16-19, 2024). The study was conducted in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology guidelines19 for cohort studies to ensure comprehensive and transparent reporting (online Supplementary Information Table 1). All clinicians administering intravenous conscious sedation were trained and experienced in remimazolam sedation according to the 2023 Intercollegiate Advisory Committee for Sedation in Dentistry (IACSD).20

Participants and setting

A total of 101 patients presenting at the Conscious Dental Sedation Service of the Maxillofacial Surgery and Dental Unit (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan) were recruited. The prospective cohort included 101 patients who received remimazolam for procedural sedation between February 2024 and October 2024. The prospective design enabled a broader patient assessment under real-life conditions, yielding more generalisable clinical practice data. Inclusion criteria included adults aged ≥18 years, patients needing sedation for minimal co-operation (anxious or odontophobic individuals with Modified Dental Anxiety Scale [MDAS] ≥14 and/or Visual Analogue Scale for Anxiety [VAS-A] ≥5, cognitive disabilities, or gag reflex grade ≥3), frail patients or those with comorbidities (e.g., older person, or with heart disease), and those undergoing invasive or prolonged surgery. Written informed consent was obtained from all participants. Exclusion criteria included contraindications to benzodiazepine sedation for prospective patients and pregnant and breastfeeding individuals. Patient selection and sedation administration followed 2020 IACSD standards for conscious sedation.21 Continuous patient monitoring included pulse oximetry, non-invasive blood pressure measurement and capnography.

Administration of remimazolam besylate for dental procedural sedation

A trained nurse prepared remimazolam besylate (Byfavo 20 mg) by reconstituting it with sodium chloride, yielding a 2.5 mg/mL solution. Based on EMA guidelines,22 an initial intravenous dose of 7 mg was given over one minute for patients <65 years, weighing ≥50 kg, and classified as American Society of Anaesthesiologists (ASA) <III (first group). For patients aged ≥65 years and/or with body weight <50 kg and ASA ≥III, a dose of 2.5-5 mg was administered over one minute (second group). Additional maintenance doses of 2.5 mg over 15 seconds were administered for the first group of patients, while for the second group, maintenance doses of 1.25-2.5 mg over 15 seconds were given as needed, with at least two minutes between doses. Maximum cumulative doses were 33 mg for the first group of patients and 17.5 mg for the second group. If the sedation target was not met after five doses within 15 minutes, sedation failure was declared, and an alternative treatment was considered. Experienced professionals administered remimazolam and monitoring was done by additional staff trained in airway and resuscitation management. Continuous cardiac and respiratory function monitoring, including capnography, was conducted, with emergency equipment, including flumazenil, readily available.

The administration of remimazolam in this study adhered strictly to the 2023 IACSD statement on remimazolam, which defines the legal and practical framework for its use in dental sedation in the UK.20 The sedation technique was classified as an operator-sedation technique, following the same clinical standards and training required for midazolam. In compliance with IACSD guidance, trained sedationists performed the administration of remimazolam pharmacology, dosing and clinical indications.

Outcome variables

The primary outcome was the procedural success rate without rescue sedatives. Secondary outcomes included: pre-operative anxiety (assessed by MDAS, VAS-A)23,24(see online Supplementary Information Table 2); tranquility before, during, and after sedation (Visual Analogue Scale for Tranquility, [VAS-T]25 - target ≥8 intra- and post-operatively); sedation depth (Ramsay sedation scale;26 see online Supplementary Information Table 3); psychomotor recovery (Newman test);27 physiological recovery (Post Anaesthetic Discharge Scoring System [PADSS] score;28 see online Supplementary Information Table 4); vital parameters (systolic blood pressure [SBP], diastolic blood pressure [DBP], mean arterial pressure [MAP], heart rate [HR], respiratory rate [RR], oxygen saturation [SpO2], end-tidal carbon dioxide [EtCO2]); anaesthesiologist intervention rate; prevalence of amnesia; adverse effects; subjective anxiolytic effect; and pain intensity during the procedure. Discharge criteria were aligned with 2020 IACSD standards.21 Patients were only discharged once they had achieved stable vital signs, full psychomotor recovery and had a responsible adult caregiver. Written and verbal post-sedation care instructions were provided, including guidance on avoiding alcohol, operating machinery, or making important decisions for the next 24 hours. In cases where full recovery was delayed beyond two hours, flumazenil administration was considered, as recommended by IACSD.21

Interventions

At the initial visit (T-1), patient selection included recording demographics, medical history, ASA classification, MDAS, VAS-A (except for cognitively disabled patients), and vital signs (SBP, DBP, MAP, HR, SpO2). Patients were instructed to adhere to the 2-4-6-8 fasting rule before the procedure.29 Follow-up calls or visits were arranged for post-operative assessment. On the day of the procedure (T0), patients confirmed their medical history and fasting compliance. Monitoring equipment was set up, and the Newman test (pre-operative score) (Fig. 1) was completed, except for cognitively disabled patients. In cooperating patients, a plexus or mandibular block was administered before sedation to confirm its efficacy and optimise the dosage of remimazolam, given its short half-life. For non-cooperative patients, the block was performed after achieving target sedation scores (VAS-T 8/10, Ramsay 2/6 or 3/6). Vital signs were measured after each remimazolam administration. After the procedure (T1), patients were monitored until a Ramsay score of 2 was reached. If full recovery was delayed beyond two hours, flumazenil was considered. Recorded data included sedation success rate, procedure time, total remimazolam dose, post-operative VAS-T, recovery time, and vital signs at discharge. Comfort and satisfaction levels were assessed verbally (VAS 1-10). Discharge required a PADSS score of 9-10 and acceptable Newman test results. On the following day (T2), patients or caregivers were interviewed to assess amnesic effects, clinical effects, subjective anxiolysis and pain (see online Supplementary Information Table 5). The specific operating protocol is shown in Table 1.

Fig. 1
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Newman test

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Table 1 Operating protocol designed for the study
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Sample size

To calculate the sample size based on the primary endpoint of ‘assessing the success rate of procedural sedation using remimazolam besylate', the following formula was used:

figure 2

Where ‘Z' is the test statistic for a chosen confidence level, ‘P' is the expected proportion, and ‘d' is the margin of error or precision.

Considering that 95%14 of subjects in the population completed the dental procedure without the use of rescue sedatives, 91 patients were needed to estimate the expected proportion, with a margin of error of 4.5% and a confidence level of 95%. Assuming an expected response rate of 90%, the study required a sample size of 101 patients.

Statistical methods

Descriptive statistics were used for all outcomes. Continuous variables were presented as means and standard deviations or as medians and interquartile ranges, depending on their distribution. Binary or categorical variables were described with counts and percentages. The primary outcome success rate was calculated by dividing the number of patients who completed the procedure without rescue sedatives by the total number of enrolled patients and multiplying by 100. For secondary outcomes involving categorical or binary data, proportions were calculated similarly.

For comparisons of continuous variables across different phases, the Kruskal-Wallis test was used. In the case of significant differences, Dunn's post-hoc test was applied for pairwise comparisons. To analyse the time from the first dose of remimazolam to patient discharge, the Kaplan-Meier estimator was applied and the survival curve was displayed. Statistical significance was set at p <0.05 for all tests and all analyses were conducted using R statistical software (v4.1.2; R Foundation for Statistical Computing, Vienna, Austria).

The study followed 2020 IACSD recommendations21 for rigorous record-keeping, including documentation of sedation dosages, patient responses and any adverse events. Continuous audit of outcomes was conducted to ensure compliance with sedation practice standards in the United Kingdom.

Results

Demographic and clinical characteristics

The study included 101 patients, with a sex distribution of 42% men and 58% women, and a mean age of 43.15 ± 19.26 years (range: 18-86; median: 37). Most participants were born in Europe (82% from Italy), with smaller groups from Bulgaria, Ukraine, Germany, Hungary, Egypt, El Salvador and Bangladesh. Average weight and height were 70.27 ± 17.10 kg and 167.44 ± 9.78 cm, resulting in a mean body mass index (BMI) of 27.22 ± 4.66, indicating a generally overweight population per World Health Organization criteria. Tobacco use was reported by 9% of participants, with ASA classifications showing 4% as ASA 1, 56% as ASA 2, and 40% as ASA 3. MDAS had a mean score of 16.87 ± 4.80, while the VAS-A indicated high general anxiety levels with a mean of 7.07 ± 2.25 (Table 2).

Table 2 Demographic, clinical and anxiety characteristics of the study population
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Patient categorisation and scheduled dental procedures

Categorisation indicated that 19% of patients were anxious, 46% odontophobic and 25% had cognitive disabilities. A low perioperative risk was observed in 34% of patients, but 40% underwent invasive or prolonged procedures, with extractions being the most common. More specific breakdowns of procedures and complexities are available in Table 3.

Table 3 Patient categorisation and distribution of scheduled dental procedures
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Prevalence of medical conditions in the study population

The study group presented a range of medical conditions, with hypertension being the most common (31%), followed by Class 1 obesity (12%). Neurological and psychiatric conditions included epilepsy (19%) and cognitive disabilities (23%). Additionally, asthma was the most frequent respiratory disease (7%), while other conditions included allergies (6%) and gastrointestinal disorders. A detailed summary is in online Supplementary Information Table 6.

Medication in the study population

Commonly prescribed medications were anticonvulsants (22%), proton pump inhibitors (20%) and benzodiazepines (15%), with other notable drugs including antihypertensives and antidepressants. Medications with lower prevalence included anticoagulants and bronchodilators (see online Supplementary Information Table 7).

Vital signs during different phases of the procedure

Distinctive patterns were observed in vital signs across phases, with notable changes in SBP and DBP, MAP, HR, RR, SpO2, and EtCO2. Kruskal-Wallis tests were conducted to assess significant differences across phases, yielding significant findings for DBP (p <0.0001), MAP (p = 0.0209), HR (p <0.0001) and SpO2 (p <0.0001), while SBP (p = 0.0693), RR (p = 0.0537) and EtCO2 (p = 0.381) were not statistically significant. Detailed results for each phase, including observed trends and values, are summarised in Table 4. Dunn's post-hoc test revealed specific differences, such as a decrease in DBP from the ‘recruitment phase' to ‘maintenance phases I to IV' and the ‘end of procedure', with p-values between 0.0198 and 0.0033. MAP significantly dropped between the ‘pre-operative phase' and ‘maintenance II' (p = 0.0229), while HR showed marked declines, particularly from ‘recruitment' to ‘maintenance III' (p = 0.0235) and ‘pre-operative' to ‘maintenance III' (p = 0.0116). SpO2 also showed specific phase differences, particularly between ‘recruitment' and certain ‘maintenance' phases (Table 5).

Table 4 Vital signs across different phases of the procedure
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Table 5 Vital signs: Dunn's multiple comparisons test
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Remimazolam dosage and sedation monitoring across procedural phases

Doses of remimazolam varied, typically 2.5 mg or 7 mg in induction phases and 2.5 mg for maintenance. Sedation levels were monitored through VAS-T, showing an increase during induction with stable values in maintenance. The Ramsay sedation scores remained predominantly at 2, indicating moderate sedation, while PADSS scores suggested readiness for discharge by the procedure's end, with details in Table 6. Kruskal-Wallis tests showed significant VAS-T differences across phases (p <0.0001), and Dunn's post-hoc analysis identified significant differences between the pre-operative, induction and end phases (Table 7).

Table 6 Remimazolam dosage, VAS-T, Ramsay and PADSS scores by phase
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Table 7 VAS-T Dunn's multiple comparisons test
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Procedure outcomes and sedation metrics

All procedures were completed successfully without rescue sedatives. The average total remimazolam dose was 15.52 ± 6.21 mg. The procedure duration averaged 26.17 ± 16.90 minutes, with a mean discharge time of 86.04 ± 22.38 minutes. Patient satisfaction was high, with VAS Comfort and VAS Satisfaction scores of 9.69 ± 1.12 and 9.73 ± 1.09, respectively (Table 8).

Table 8 Timing, total remimazolam administration and outcomes
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Psychomotor recovery was evaluated using the Newman test, showing significant improvement (pre-operative score: 6.62 ± 6.16 versus post-operative score: 3.52 ± 4.07; p <0.0001 via Kruskal-Wallis test). Dunn's post-hoc test further supported significant differences between pre- and post-sedation Newman scores (Table 9).

Table 9 Newman scores Dunn's multiple comparisons test
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Discharge timeline and recovery pattern following remimazolam sedation in dental procedures

The discharge timeline illustrates recovery efficiency after sedation with remimazolam in dental procedures. All 101 patients remained sedated initially, with the first discharge occurring at 30 minutes. Discharges gradually increased, peaking between 60 and 90 minutes, when the number of sedated patients dropped significantly from 80 to 27. After 90 minutes, discharges slowed, with the last patient discharged at 140 minutes, completing recovery in 150 minutes. The modified Kaplan-Meier curve (Fig. 2) highlights this peak discharge period, providing a detailed view of patient recovery times.

Fig. 2
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Kaplan Meier curve showing discharge timeline of 101 patients following intravenous sedation with remimazolam in dental procedures

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Patient experience and adverse effects of remimazolam sedation

A low percentage of patients (35%) recalled the final part of the procedure, while most (65%) reported complete anterograde amnesia and being asleep the entire time. Most patients preferred a sleep-inducing experience during the procedure (74%), while 26% preferred to feel calm. Patient comfort was high, with 69% reporting ‘high' anxiolytic effects and minimal adverse effects, including occasional headaches and mild syncope, demonstrating remimazolam's favourable safety profile. The subjective assessment of sedation was highly favourable, with 69% rating the anxiolytic effect as ‘high' and 15% as ‘very high'. These findings are summarised in Table 10.

Table 10 Telephone interview results performed the day after the procedure
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Discussion

This observational study comprehensively examined patient demographics, clinical characteristics, procedural outcomes and physiological responses in a population undergoing dental procedures with remimazolam sedation. The findings highlight remimazolam's efficacy, safety and patient experience, underscoring its potential advantages in procedural sedation, especially within dental practice. Notably, to the best of our knowledge, this research represents the first investigation of remimazolam besylate for dental sedation in Europe. This lack of European data underscores the novelty and clinical significance of our findings, providing a foundational evidence base for the integration of remimazolam in dental sedation practices.

Our study cohort consisted of 101 patients, predominantly of European origin, with a mean age of 43.15 years and a mean BMI of 27.22, classifying them as overweight. This demographic reflects a typical clinical population requiring sedation, often presenting with comorbidities that complicate sedation. In our cohort, 56% were classified as ASA 2 and 40% as ASA 3, indicating a moderate-risk group. This distribution is consistent with findings by Cowell et al.30 and supported by Sun et al.,15 who also noted similar ASA distributions in sedated patient populations. Furthermore, we agree with Kim et al.16 that remimazolam's short action profile, lack of accumulation and minimal cardiovascular impact make it a highly suitable option for these higher-risk patients.16 Finally, our study primarily involved a white population, with 89% of participants being of European ethnicity, whereas most of the available literature evaluates the use of remimazolam in patients of Asian ethnicity.31 This distinction provides valuable insights into the efficacy and safety of remimazolam in a different ethnic group, broadening the understanding of its clinical application across diverse populations.

The primary outcome of this study was the procedural success rate with remimazolam besylate (Byfavo 20 mg), defined as successful procedure completion without the need for rescue sedatives. We achieved a 100% procedural success rate, with all patients reaching adequate sedation levels and no need for alternative sedative interventions. This aligns with findings from Guo et al.14 and Sun et al.,15 which documented high success rates with remimazolam in dental and oral surgery procedures. In contrast, studies on midazolam, such as those by Cowell et al.,30 report lower success rates due to higher rates of adverse events or suboptimal sedation in patients with significant comorbidities, highlighting remimazolam's reliability in complex cases. Additionally, Swart et al.,18 in a pilot study on office-based dental sedation, also reported a high procedural success rate with remimazolam, though with some minor adverse events, which are manageable in a clinical setting. This further supports remimazolam's suitability for dental sedation, where its efficacy in various settings is validated.

Our study confirmed the high efficacy and safety of remimazolam in moderate- to high-risk dental patients (ASA II and III), demonstrating its predictable recovery profile with a mean recovery time of 49 minutes. These findings align with Stöhr et al.,32 who reported remimazolam's stable pharmacokinetic profile even in patients with hepatic or renal impairment. Although severe hepatic impairment increased exposure by 38.1%, recovery time was only modestly prolonged (16.7 minutes versus 8 minutes in healthy individuals). Our results similarly showed no significant delay in recovery or adverse pharmacokinetic effects, further supporting remimazolam's reliability across diverse patient profiles.

Pre-operative anxiety was measured using the MDAS and the VAS-A. The cohort had a mean MDAS score of 16.87 and a mean VAS-A score of 7.07, reflecting high general anxiety. With 46% of patients classified as odontophobic and 11% with needle phobia, effective anxiolytic control was essential. Studies on midazolam, such as those by Lawler et al.,33 highlight challenges in managing high dental anxiety, often requiring higher doses, which can increase adverse effects. Remimazolam, with comparable anxiolytic efficacy to midazolam but a superior safety profile, according to Li et al.,9 presents a safer alternative for highly anxious or respiratory-sensitive patients. Swart et al.18 observed high patient satisfaction and a reduction in pre-operative anxiety with remimazolam, corroborating its effectiveness in managing dental anxiety - a critical factor in successful sedation outcomes.

Tranquility levels were assessed pre-, intra- and post-sedation using the VAS-T, targeting pre-sedation scores of <8 and intra- and post-sedation scores of ≥8. Remimazolam consistently maintained high tranquility levels throughout the procedure, which is crucial for patient cooperation in dental settings. These findings align with results by Guo et al.14 and Sun et al.15 Compared to traditional agents like midazolam, remimazolam offers stable anxiolytic effects without prolonged sedation.17,34

Sedation depth was evaluated using the Ramsay Sedation Scale, with optimal scores of 2/6 or 3/6. Most patients achieved a score of 2, indicating moderate sedation suitable for dental procedures. These findings are consistent with the literature on remimazolam's efficacy in achieving sedation levels appropriate for conscious sedation in dentistry,35 as outlined by IACSD guidelines.21 Unlike midazolam, which sometimes necessitates additional medications for enhanced anxiolysis, remimazolam has demonstrated predictable pharmacokinetics while maintaining conscious sedation parameters.

Psychomotor recovery was assessed using the Newman test,27 comparing the number of points omitted before and after sedation. The mean recovery time was 49 minutes, underscoring remimazolam's suitability for outpatient settings. Chen et al.36 observed similar findings, noting faster recovery with remimazolam compared to midazolam, enhancing efficiency in busy clinical environments. Oue et al.17 also documented rapid recovery times with remimazolam, reinforcing its value for outpatient dental procedures where quick discharge is essential.

Physiological recovery was measured with the PADSS, with scores of 9 or 10 indicating readiness for discharge. Most patients were discharged within 60-90 minutes, reinforcing remimazolam's effectiveness for rapid recovery, as supported by studies from Chen et al.36 and Ito et al.37

Key vital parameters, including SBP, DBP, MAP, HR, RR, SpO2, and EtCO2, remained clinically stable throughout procedures, despite statistically significant variations, with changes consistently <20% from pre-operative values, as outlined in the PADSS criteria. SBP and DBP stabilised after initial fluctuations, consistent with studies reporting cardiovascular stability with remimazolam.14 MAP and HR increased during induction but quickly stabilised, contrasting with midazolam, which often has prolonged cardiovascular effects. RR, SpO2 and EtCO2 remained stable, supporting remimazolam's advantage in minimising respiratory depression.38 Swart et al.18 also observed stability in cardiovascular parameters with remimazolam, further supporting its safe use in outpatient dental sedation.

Anaesthesiologist intervention was not needed, demonstrating remimazolam's reliability in maintaining stable sedation without the need for additional support, especially compared to midazolam.30 This is advantageous in outpatient dental practices, where stable sedation with minimal oversight is desirable.

Anterograde amnesia was observed in 65% of patients, who were unable to recall the time when the dental procedure ended, highlighting the ability of remimazolam to effectively induce amnesia while minimising post-sedation recollection. This balance is particularly beneficial for reducing procedural anxiety, as reflected by the 74% of patients who preferred to sleep during the procedure. These findings are consistent with the observations of Dahiya et al.,39 further highlighting remimazolam's suitability for outpatient dental sedation.

Adverse effects were minimal, with only minor headache and vomiting cases reported, consistent with findings from Kim et al.,16 who observed fewer post-operative nausea and vomiting events with remimazolam compared to propofol. Our results reinforce remimazolam's favourable safety profile, particularly in outpatient settings where quick recovery and minimal post-sedation symptoms are essential.

Subjective anxiolytic effects were rated highly by most patients, supporting remimazolam's effectiveness in managing pre-operative anxiety and ensuring a comfortable experience. These outcomes align with findings by Guo et al.,14 highlighting remimazolam's stable anxiolytic profile, which benefits procedural comfort and cooperation in dental settings.

Most patients rated intra-operative pain as low to moderate, suggesting that remimazolam provides adequate analgesic support for dental procedures. This aligns with Sun et al.,15 who reported that remimazolam maintains patient comfort without needing additional analgesics, supporting its use in procedures involving moderate discomfort.

The study highlights key limitations and future directions in the use of remimazolam for procedural sedation, particularly in dental practice. One significant limitation noted is the subjective nature of the Ramsay Sedation Scale, which could lead to variability in the assessment of sedation depth. Future studies could benefit from using objective measures like the Bispectral Index to improve sedation assessment accuracy. This study did not account for weight-related dosing variations, which could impact remimazolam distribution and clearance. While we found no significant correlation between weight and Ramsay scores, larger studies could explore this relationship further. Future research should also consider randomised controlled trials for a more robust comparison with other sedatives. In addition, we will plan to conduct a study to refine the current EMA-recommended dosing protocol. Specifically, in the context of conscious sedation in dentistry - where anxiolysis and careful titration to achieve the minimum effective concentration of the drug are priorities - we intend to demonstrate that the induction dose of remimazolam should start with lower doses (e.g., 2.5-5.0 mg) rather than the 7 mg currently recommended for patients younger than 65 years, weighing ≥50 kg and classified as ASA <III. This approach aligns more closely with the US Food and Drug Administration (FDA)-recommended dosing guidelines and may reduce unnecessary drug exposure and adverse effects. However, we do not agree with the FDA's limitation of remimazolam use to procedures lasting a maximum of 30 minutes, as our study completed interventions lasting up to 104 minutes with excellent safety and efficacy outcomes. Additionally, further studies will investigate the application of remimazolam in paediatric populations, as well as in individuals with disabilities. For the latter group, the approval and testing of intranasal administration of remimazolam will be pursued to provide a more effective and less invasive approach for non-cooperative patients. Finally, a dedicated infusion pump tailored for remimazolam delivery will be developed to enhance the precision and adaptability of its use in longer and more complex procedures.

Conclusion

This prospective observational study provides important insights into the use of remimazolam for procedural sedation in dental practice, particularly within a European cohort, where its application is still relatively novel. The findings demonstrate remimazolam's strong efficacy, safety and positive impact on patient experience, highlighted by a 100% procedural success rate and minimal adverse events. The sedative's ability to maintain cardiovascular stability and minimise respiratory depression makes it a suitable choice for patients with complex health profiles, particularly those classified as ASA II and III. Remimazolam consistently achieved sedation and tranquility levels that supported procedural success, while enabling rapid recovery and discharge. These advantages, including enhanced patient comfort, cooperation and quick recovery, underscore remimazolam as a preferable option in outpatient dental settings compared to traditional agents like midazolam.