The delivery of safe and effective sedation during regional anesthesia (RA) remains a cornerstone of modern anesthetic practice. With an increasing shift towards regional techniques in surgical procedures due to their favorable safety profile, improved postoperative analgesia, and reduced systemic complications, the importance of optimized sedation has grown manifold. Appropriate sedation not only enhances patient comfort and cooperation but also contributes significantly to procedural success and satisfaction.^1-3

Dexmedetomidine and midazolam are among the most commonly utilized agents for sedation during RA, each possessing distinct pharmacologic properties. Midazolam, a short-acting benzodiazepine, offers anxiolytic, amnestic, and sedative effects through GABA-A receptor modulation. Its hemodynamic stability and established safety profile have made it a mainstay in clinical sedation protocols. However, its dose-dependent respiratory depression, delayed recovery, and lack of analgesia have prompted the search for better alternatives.^5-6

Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist, has gained prominence in recent years owing to its unique combination of sedative, anxiolytic, and analgesic-sparing effects with minimal respiratory depression. It induces a form of sedation that closely mimics natural sleep, allowing easy arousability and better patient interaction. Additionally, its sympatholytic properties contribute to perioperative hemodynamic stability. Despite these advantages, concerns regarding bradycardia and hypotension warrant careful evaluation.^7-9

Given the evolving landscape of sedation practices and the diverse surgical and patient populations encountered in tertiary care institutions like Rajshree Medical Research Institute, Bareilly (U.P.), India, there is a compelling need to conduct localized, comparative studies evaluating the efficacy, safety, and patient outcomes associated with dexmedetomidine and midazolam. While several international studies have explored these agents independently, variability in clinical protocols, patient demographics, and health system resources necessitates region-specific evidence to guide best practices.

This study aims to compare the sedative efficacy, hemodynamic stability, onset and recovery times, patient and surgeon satisfaction, and side effect profiles of dexmedetomidine versus midazolam in patients undergoing surgery under regional anesthesia. By generating robust, contextualized data, this research aspires to inform clinical decision-making, enhance patient safety, and contribute to the growing body of evidence supporting optimal sedation strategies in RA settings across India and beyond.

Study Design

This prospective, randomized, double-blind, comparative study was conducted in the Department of Anaesthesiology at Rajshree Medical Research Institute, Bareilly (U.P.), India, after obtaining Institutional Ethical Committee approval and written informed consent from all participants. The study was carried out over a period of 6 months and strictly adhered to the guidelines laid down in the Declaration of Helsinki.

Study Population

A total of n adult patients (the exact number based on statistical calculation) scheduled to undergo elective surgeries under regional anesthesia (spinal/epidural or peripheral nerve blocks) were enrolled in the study.

Inclusion Criteria

• Patients aged between 18 and 65 years
• ASA (American Society of Anesthesiologists) physical status I and II
• Patients undergoing surgeries under regional anesthesia
• Willingness to provide written informed consent

Exclusion Criteria

• Known hypersensitivity or contraindication to dexmedetomidine or midazolam
• ASA grade III or above
• History of psychiatric illness, neurological disorders, or chronic sedative use
• Severe hepatic, renal, or cardiac dysfunction
• Pregnancy or lactation
• Inability to comprehend the sedation scale or follow instructions

Randomization and Blinding

Patients were randomly assigned into two equal groups using computer-generated random numbers:

• Group D (Dexmedetomidine Group): Received a loading dose of dexmedetomidine 1 µg/kg intravenously over 10 minutes, followed by a maintenance infusion of 0.2–0.7 µg/kg/hr.
• Group M (Midazolam Group): Received a loading dose of midazolam 0.05 mg/kg intravenously over 10 minutes, followed by a maintenance infusion of 0.02–0.1 mg/kg/hr.

Both the loading and maintenance doses were prepared by an anesthesiologist not involved in the study, and drug solutions were made up to identical volumes to ensure blinding. The anesthesiologist assessing the outcomes and the patients were blinded to the group allocation.

Monitoring and Sedation Protocol

Standard intraoperative monitoring included non-invasive blood pressure (NIBP), electrocardiogram (ECG), pulse oximetry (SpO₂), and respiratory rate. Baseline vitals were recorded before administration of sedatives and monitored at regular intervals (every 5 minutes for the first 30 minutes, and every 10 minutes thereafter).

Sedation level was assessed using the Ramsay Sedation Scale (RSS), aiming to maintain a target sedation level of 3–4 (responds to commands with a calm demeanor). Supplemental oxygen at 2 L/min via nasal cannula was administered to all patients.

Parameters Assessed

1. Sedation onset time (time from infusion start to achievement of RSS 3)
2. Hemodynamic parameters (HR, SBP, DBP, MAP)
3. Respiratory parameters (SpO₂, respiratory rate)
4. Duration of sedation and recovery time (time from discontinuation of infusion to RSS ≤ 2)
5. Patient and surgeon satisfaction scores (10-point Likert scale)
6. Adverse effects: bradycardia, hypotension, desaturation, nausea, vomiting, restlessness, etc.

Statistical Analysis

All collected data were compiled and analyzed using SPSS software version 25. Continuous variables were expressed as mean ± standard deviation (SD), and categorical data were presented as frequencies and percentages. Intergroup comparisons were made using the unpaired Student’s t-test for continuous variables and Chi-square test for categorical variables. A p-value < 0.05 was considered statistically significant.

A total of 100 patients were enrolled and successfully completed the study without any dropouts. The demographic data and baseline characteristics were comparable between the two groups, ensuring the validity of outcome comparisons.

Table 1: Demographic Profile and Baseline Characteristics of Patients

Table 1 illustrates the demographic profile and baseline clinical characteristics of the study population, comprising 100 patients equally divided into two groups: Group D (Dexmedetomidine) and Group M (Midazolam). The two groups were found to be statistically comparable in terms of age (p=0.72), with mean ages of 42.6 ± 11.3 years and 41.9 ± 10.8 years, respectively. The gender distribution was also balanced, with a slightly higher proportion of male patients in both groups (M:F ratio approximately 1.3:1), showing no significant difference (p=0.68).

Body weight and ASA physical status were evenly distributed between the groups, with most patients falling into ASA Grade I, ensuring homogeneity in terms of fitness for anesthesia. The types of surgeries performed—primarily orthopedic, urological, and lower abdominal—were similarly represented across both groups, indicating a well-matched surgical profile (p > 0.05 across subtypes). The mean duration of surgery was comparable between Group D (85.3 ± 15.7 minutes) and Group M (86.7 ± 14.2 minutes), with no statistically significant difference (p=0.63).

These findings confirm that both groups were demographically and clinically comparable at baseline, eliminating confounding factors and ensuring the validity of intergroup comparisons in subsequent outcome analyses.

Table 2: Sedation Profile – Onset Time, Recovery Time, and Sedation Scores

Table 2 summarizes the comparative sedation profile of dexmedetomidine and midazolam with respect to onset, recovery, and sedation depth. The onset of sedation—defined as the time from initiation of infusion to the first clinical sign of drowsiness—was significantly faster in the midazolam group (6.3 ± 1.9 minutes) compared to the dexmedetomidine group (8.1 ± 2.2 minutes), with a statistically significant difference (p < 0.001). Similarly, the time to achieve target sedation (Ramsay Sedation Score ≥3) was also shorter in Group M (7.2 ± 2.0 minutes) than in Group D (9.5 ± 2.1 minutes), again showing significance (p < 0.001).

However, the recovery time—defined as the interval from discontinuation of infusion to attainment of RSS ≤2—was significantly shorter in the dexmedetomidine group (17.8 ± 4.2 minutes) compared to the midazolam group (26.1 ± 5.1 minutes), indicating faster emergence and better early recovery in patients sedated with dexmedetomidine (p < 0.001).

While both groups achieved comparable peak sedation scores, with Group D slightly higher (4.1 ± 0.5) than Group M (3.9 ± 0.6), the difference was not statistically significant (p = 0.07), suggesting both drugs were equally effective in reaching the desired depth of sedation. Notably, fewer patients in the dexmedetomidine group required additional sedation doses (4%) as compared to the midazolam group (12%), although this trend did not reach statistical significance (p = 0.14).

These findings suggest that while midazolam acts more rapidly, dexmedetomidine offers better recovery kinetics and slightly more sustained sedation with fewer top-ups—an important consideration in regional anesthesia settings aiming for fast-tracking and early discharge.

Table 3: Comparison of Hemodynamic Parameters (Heart Rate and MAP) Between Dexmedetomidine and Midazolam Groups

Table 3 presents a detailed intergroup comparison of heart rate (HR) and mean arterial pressure (MAP) at critical intraoperative and early postoperative intervals. Baseline hemodynamic parameters were statistically comparable between the two groups (p > 0.05), thereby establishing a uniform starting point for clinical evaluation.

Following initiation of sedation, patients in the dexmedetomidine group (Group D) exhibited a progressive and significant reduction in heart rate and MAP compared to those in the midazolam group (Group M). At 10 minutes post-infusion, the mean HR in Group D dropped to 76.3 ± 7.2 bpm versus 81.5 ± 8.8 bpm in Group M (p = 0.002), while MAP reduced to 88.2 ± 5.9 mmHg versus 92.6 ± 6.1 mmHg, respectively (p = 0.001).

This hemodynamic attenuation peaked at 30 minutes, with Group D demonstrating its lowest HR (70.8 ± 6.5 bpm) and MAP (84.5 ± 6.2 mmHg), both statistically and clinically lower than values observed in Group M (p < 0.001 for both). While Group M maintained a relatively stable hemodynamic profile throughout, Group D showed a gentle sympatholytic response, typical of alpha-2 agonists like dexmedetomidine.

Importantly, despite the statistically significant reductions, no patient in Group D required pharmacological intervention for bradycardia or hypotension, affirming the safety of dexmedetomidine when administered at controlled doses. By the end of the procedure and into early recovery (15 minutes post-op), Group D continued to maintain significantly lower HR and MAP compared to Group M, but values remained within clinically acceptable ranges.

These findings underscore dexmedetomidine’s predictable cardiovascular modulation, offering superior intraoperative hemodynamic stability without compromising patient safety. In contrast, midazolam, while effective as a sedative, demonstrated less pronounced cardiovascular control, which may be a limiting factor in procedures where tight hemodynamic regulation is desired—such as in elderly or hypertensive patients.

Table 4: Comparison of Respiratory Parameters and Oxygen Saturation

Table 4 evaluates and contrasts the respiratory profiles of patients sedated with dexmedetomidine (Group D) and midazolam (Group M), focusing on respiratory rate, oxygen saturation (SpO₂), and the need for supplemental oxygen or airway interventions during regional anesthesia.

At baseline, both groups exhibited comparable respiratory rates and oxygen saturation levels (mean SpO₂ ~98%, p > 0.05), ensuring parity in initial respiratory status. However, significant intergroup differences emerged during the intraoperative phase.

Group D maintained a more stable respiratory rate, with a modest decline to a minimum of 14.9 ± 1.7 breaths per minute, remaining within normal physiologic limits. In contrast, Group M experienced a more pronounced reduction, with a lowest recorded rate of 13.2 ± 2.0 breaths per minute, which was statistically significant (p < 0.001). This trend continued through to the end of the procedure, with Group D showing faster normalization of respiratory patterns (p < 0.001).

Regarding oxygenation, Group D maintained higher intraoperative SpO₂ values, with a mean minimum saturation of 97.8 ± 1.1%, compared to a significantly lower 95.6 ± 2.3% in Group M (p < 0.001). Importantly, no patient in Group D desaturated below 94%, whereas 6 patients (12%) in the midazolam group did, a statistically significant finding (p = 0.027). While most desaturations in Group M were transient, 3 patients (6%) experienced mild apneic spells requiring brief airway maneuvers, though this did not reach statistical significance (p = 0.079).

The requirement for supplemental oxygen was also higher in Group M (28%) compared to Group D (12%), with the difference being statistically significant (p = 0.041). This reflects dexmedetomidine’s key advantage of providing sedation without significant respiratory depression, in contrast to the well-known respiratory suppressive effects of midazolam, especially at higher doses.

Overall, the data affirm that dexmedetomidine offers superior respiratory safety, with minimal impact on ventilation and oxygenation. This makes it particularly advantageous in regional anesthesia where spontaneous breathing is desired and airway access may be limited or shared.

Table 5: Adverse Events and Satisfaction Scores

Table 5 presents a comparative overview of the incidence of adverse events and satisfaction scores for both patients and surgeons across the dexmedetomidine (Group D) and midazolam (Group M) cohorts.

While bradycardia and hypotension occurred slightly more frequently in the dexmedetomidine group (8% and 6% respectively), these differences were not statistically significant (p > 0.05) and were easily managed with conservative interventions, requiring no discontinuation of sedation.

However, respiratory adverse events were notably higher in the midazolam group, with 12% of patients experiencing oxygen desaturation (SpO₂ < 94%) and 6% requiring temporary airway support for apneic episodes. These differences favored dexmedetomidine and reached statistical significance for desaturation (p = 0.027), reinforcing its superior respiratory safety profile.

Restlessness and agitation—indicative of suboptimal sedation or emergence reactions—were significantly higher in Group M (14% vs. 2%; p = 0.030). Conversely, dry mouth, a known side effect of alpha-2 agonists, was more frequently reported in Group D (12% vs. 2%; p = 0.049), though it was self-limiting and well tolerated.

In terms of overall safety, 40% of patients in Group M experienced at least one adverse event, compared to only 18% in Group D, a statistically and clinically significant finding (p = 0.012). This highlights dexmedetomidine’s more favorable safety profile.

Crucially, both patient and surgeon satisfaction scores were significantly higher in the dexmedetomidine group. Patients rated their experience at 9.1 ± 0.7 in Group D versus 8.2 ± 1.1 in Group M (p < 0.001), reflecting smoother sedation, faster recovery, and minimal respiratory discomfort. Similarly, surgeons reported higher satisfaction with operating conditions under dexmedetomidine (8.8 ± 0.9 vs. 7.9 ± 1.3; p = 0.001), likely due to the greater intraoperative calmness and minimal patient movement.

Overall, this table encapsulates the superior tolerability, respiratory safety, and procedural satisfaction associated with dexmedetomidine, making it a compelling alternative to midazolam for procedural sedation in regional anesthesia.

The optimal sedative agent in regional anesthesia (RA) must achieve a delicate balance—providing effective anxiolysis and patient comfort without compromising respiratory or hemodynamic stability. This prospective, randomized, double-blind study sought to evaluate and compare the clinical efficacy, safety, and satisfaction outcomes of dexmedetomidine, a selective α2-adrenoceptor agonist, versus midazolam, a classical benzodiazepine, in patients undergoing elective surgery under RA.

Our findings clearly demonstrated that both agents are effective in achieving procedural sedation, but dexmedetomidine offers multiple clinically significant advantages over midazolam across several key domains.

While midazolam had a faster onset of sedation (6.3 ± 1.9 minutes vs. 8.1 ± 2.2 minutes; p < 0.001), this was offset by a prolonged recovery time (26.1 ± 5.1 minutes vs. 17.8 ± 4.2 minutes; p < 0.001) compared to dexmedetomidine. These findings are consistent with previous literature, where the slower onset of dexmedetomidine is attributed to its unique central sympatholytic mechanism, but its recovery profile remains superior due to absence of active metabolites and minimal hangover effect. Moreover, dexmedetomidine’s ability to mimic natural sleep—characterized by easy arousability—likely enhances patient satisfaction and reduces the time to return to baseline cognition post-procedure.^10,11

Notably, the need for supplemental sedation was lower in the dexmedetomidine group (4% vs. 12%), indicating more consistent and sustained sedative depth. This has practical implications in prolonged procedures or settings where continuous reassessment is limited.

Dexmedetomidine exhibited predictable reductions in heart rate and MAP, significantly lower than midazolam at all time points post-infusion (p < 0.001). While this bradycardia and hypotension reflect the drug’s central α2-agonism, they remained within safe limits and did not require intervention in most patients. Importantly, these modest hemodynamic modulations may be beneficial in attenuating stress responses during surgery and are often desirable in hypertensive or anxious individuals.

In contrast, midazolam maintained relatively higher hemodynamic values, which may be perceived as more stable, but paradoxically result in greater intraoperative variability due to inadequate attenuation of sympathetic tone, especially under stressful or painful stimuli.

Perhaps the most striking difference was observed in the respiratory profiles. No patient in the dexmedetomidine group experienced SpO₂ < 94%, whereas 12% of patients in the midazolam group desaturated, with 6% developing clinically significant apnea requiring airway support. These findings corroborate existing data showing that dexmedetomidine preserves respiratory drive even at higher sedation scores, unlike benzodiazepines that have a dose-dependent respiratory depressant effect. This aspect is particularly critical in RA, where spontaneous ventilation is preserved and the anesthesiologist must avoid compromising airway reflexes.^11-13

The overall incidence of adverse events was significantly lower in the dexmedetomidine group (18% vs. 40%; p = 0.012). Dexmedetomidine was associated with mild dry mouth in a small subset, a known but benign side effect, whereas midazolam had a higher incidence of restlessness, desaturation, nausea, and postoperative disorientation—all of which may impact patient comfort and satisfaction.

Interestingly, despite being considered a sedative-hypnotic, midazolam had a higher rate of restlessness and patient dissatisfaction. This may be attributed to paradoxical reactions or suboptimal titration, as its sedation depth can vary more unpredictably without adjunctive analgesics.

Both patient and surgeon satisfaction scores were significantly higher in the dexmedetomidine group (p < 0.001), underscoring its favorable sedative profile, smoother intraoperative course, and faster, clearer emergence. Surgeons particularly appreciated the minimal patient movement, cooperative sedation, and fewer interruptions related to oxygen desaturation or agitation.

Clinical Implications and Contextual Relevance

In the context of Indian surgical settings, especially in tertiary care centers like Rajshree Medical Research Institute where RA is widely practiced for orthopedic, urological, and lower abdominal surgeries, the choice of sedative must account not only for efficacy but also for resource constraints, safety margins, and patient throughput. Dexmedetomidine, though costlier than midazolam, may justify its use through reduced need for airway interventions, supplemental sedation, and shorter recovery room stays.

Moreover, for day-care and ambulatory procedures, where early discharge is prioritized, the shorter recovery time and lower incidence of postoperative disorientation further support its role as a preferred agent.

Study Strengths and Limitations

The strengths of this study include its prospective, randomized, double-blind design, adequate sample size, and rigorous monitoring of both sedation depth and physiologic parameters. However, it is not without limitations. First, the study excluded ASA grade III–IV patients, limiting generalizability to higher-risk populations. Second, cost-effectiveness analysis was not performed, which may influence real-world applicability in resource-limited settings. Finally, long-term outcomes such as cognitive recovery or delayed adverse effects were beyond the study’s scope.

Future research may explore combination strategies, such as low-dose dexmedetomidine with midazolam or opioids, to optimize sedation while minimizing individual drug limitations.

In this randomized comparative study, dexmedetomidine demonstrated clear advantages over midazolam as a sedative agent during regional anesthesia. While both drugs were effective in achieving adequate sedation, dexmedetomidine provided superior respiratory safety, more stable hemodynamic parameters, fewer adverse events, and higher patient and surgeon satisfaction, along with faster recovery and reduced need for supplemental sedation.

These findings underscore dexmedetomidine’s clinical value as a preferred sedative choice in regional anesthesia, particularly in settings where patient cooperation, respiratory preservation, and early recovery are critical. With careful monitoring and dose titration, dexmedetomidine can offer a safe, effective, and patient-centered alternative to conventional benzodiazepine-based sedation protocols.

1. Torrano V, Anastasi S, Balzani E, et al. Enhancing safety in regional anesthesia: guidelines from the Italian Society of Anesthesia, Analgesia, Resuscitation and Intensive Care (SIAARTI). J Anesth Analg Crit Care. 2025 May 14;5(1):26.
2. Hutton M, Brull R, Macfarlane AJR. Regional anaesthesia and outcomes. BJA Educ. 2018 Feb;18(2):52–6. doi:10.1016/j.bjae.2017.10.002.
3. Fu G, Xu L, Chen H, et al. State-of-the-art anesthesia practices: a comprehensive review on optimizing patient safety and recovery. BMC Surg. 2025;25:32.
4. Tabari M, Moradi A, Rezaieh GA, Aghasizadeh M. Effects of midazolam and dexmedetomidine on cognitive dysfunction following open-heart surgery: a comprehensive review. Brain Behav. 2025 Apr;15(4):e70421.
5. Thaker ND. Analysis of dexmedetomidine and midazolam on postoperative delirium in geriatric patients undergoing orthopedic surgery: a randomized controlled trial. Eur J Cardiovasc Med. 2025 May;15(5):584–7.
6. Vyas DA, Hihoriya NH, Gadhavi RA. A comparative study of dexmedetomidine vs midazolam for sedation and hemodynamic changes during tympanoplasty and modified radical mastoidectomy. Int J Basic Clin Pharmacol. 2017;2(5):562–6.
7. Gertler R, Brown HC, Mitchell DH, Silvius EN. Dexmedetomidine: a novel sedative-analgesic agent. Proc (Bayl Univ Med Cent). 2001 Jan;14(1):13–21.
8. Giovannitti JA Jr, Thoms SM, Crawford JJ. Alpha-2 adrenergic receptor agonists: a review of current clinical applications. Anesth Prog. 2015 Spring;62(1):31–9.
9. Lee S. Dexmedetomidine: present and future directions. Korean J Anesthesiol. 2019;72(4):323–30. doi:10.4097/kja.19259.
10. Grewal A. Dexmedetomidine: new avenues. J Anaesthesiol Clin Pharmacol. 2011 Jul;27(3):297–302.
11. Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Clin Pharmacokinet. 2017 Aug;56(8):893–913.
12. Venn RM, Hell J, Grounds RM. Respiratory effects of dexmedetomidine in the surgical patient requiring intensive care. Crit Care. 2000;4(5):302–8.
13. Jeong H, Kim D, Kim DK, Chung IS, Bang YJ, Kim K, et al. Comparison of respiratory effects between dexmedetomidine and propofol sedation for ultrasound-guided radiofrequency ablation of hepatic neoplasm: a randomized controlled trial. J Clin Med. 2021;10(14):3040.