Preoperative anxiety is a common and clinically relevant concern among patients scheduled for surgery under general anesthesia.[1] It can be caused by anxiety about the surgery, general anesthesia, and pain after surgery, potential complications, and the expectation of an uncertain outcome.[2] The prevalence rate varies widely among different populations and different assessment methods, with studies indicating that 60-80% of surgical patients might have a level of preoperative anxiety.[3, 4] The pooled prevalence of 55.7% (95% CI: 48.6-62.9%) was reported for 27 studies with 5,575 patients in low- and middle-income countries, and an even higher prevalence was reported for the Asian population of 62.6%.[5]  Preoperative anxiety is not just an emotional reaction, but may also be associated with greater anesthetic and analgesic needs, postoperative pain, slow recovery and other unfavourable peri-operative outcomes.[6]

Pharmacological premedication is often applied to decrease anxiety, make patients co-operative and induce sedation prior to induction of anesthesia.[7] Midazolam, a short-acting benzodiazepine, has traditionally been one of the most commonly used premedicates due to its properties of anxiolysis, sedation and amnesia.[8] However, excessive sedation, respiratory depression, and sometimes psychomotor recovery delay have been reported with its use in some patients.[9] Furthermore, a randomized clinical trial has indicated that preoperative anxiolysis with midazolam is not invariably beneficial for postoperative quality of recovery, casting doubt on its utility for routine use simply for its anxiolytic effect.[10]

The highly selective α2-adrenergic receptor agonist dexmedetomidine has become an alternative premedication due to its ability to induce sedation and anxiolysis while maintaining spontaneous respiration.[11] It has also been suggested that its sympatholytic properties could reduce cardiovascular and stress reactions to laryngoscopy and intubation.[12] Randomized trials that have examined dexmedetomidine versus midazolam have shown that dexmedetomidine can effectively reduce preoperative anxiety and sedation, with results that have been inconsistent across various doses, routes of administration, and patient populations.[13, 14] Importantly, evidence beyond anxiety is also evolving: A meta-analysis of perioperative intravenous dexmedetomidine in adults undergoing elective surgery revealed an association with better postoperative quality of recovery and decreased postoperative nausea and vomiting.[15]

These data, however, do not preclude the comparability of dexmedetomidine and midazolam when the two are used specifically as premedications before surgery, especially when both preoperative anxiolysis and postoperative recovery are taken into account. Previous research has tended to focus on sedation, hemodynamic responses, or simply individual postoperative outcomes; less emphasis has been placed on the more general concept of early quality of recovery after general anesthesia. A recent randomized study in elective laparoscopy also demonstrates ongoing interest in directly comparing these two agents and their effects perioperatively.[16]  Thus, the choice of one premedication strategy over the other would benefit from an understanding of whether dexmedetomidine offers improved benefits over the traditional midazolam-based approach regarding pre-operative anxiety control and early post-operative recovery. Accordingly, the present study aimed to assess the impact of dexmedetomidine as compared to midazolam premedication on preoperative anxiety and early quality of recovery in patients who were undergoing general anesthesia. The purpose of this study was to evaluate and compare anxiety levels before surgery with the two premedication regimens and to determine their effect on early postoperative quality of recovery.

A prospective cohort study was carried out at Mayo Hospital, King Edward Medical University in Lahore for a duration of 6 months from December 2025 to June 2026. The sample size was determined with the software OpenEpi for the comparison of two independent proportions with a 95% confidence level and an 80% power. Previous studies comparing dexmedetomidine and midazolam for sedation and anxiety preoperatively have shown clinically relevant differences; thus, a minimum of 50 patients per group was considered sufficient.[17] A previous adult study included 100 patients, with 50 receiving midazolam and 50 receiving dexmedetomidine, and directly compared their preoperative anxiety and sedation responses.[17] So, the calculated sample size was 100 patients in each group: 50 patients in the dexmedetomidine group and 50 patients in the midazolam group. To compensate for approximately 10% potential loss to follow-up or incomplete postoperative assessment, the final sample size was increased to 110 patients, with 55 patients in each group. A consecutive sampling technique was used. Patients aged 18-60 years, ASA physical status I or II, planned for elective surgery under general anesthesia, and who were premedicated with dexmedetomidine or midazolam were included. Patients who were able to complete the anxiety and quality-of-recovery questionnaires and gave written informed consent were included. Patients with a history of allergy or contraindication to dexmedetomidine or midazolam, severe cardiovascular, respiratory, hepatic, renal, psychiatric, or cognitive disorder, chronic sedative or anxiolytic use, emergency surgery, and poor communication or inability to complete post-operative assessment were excluded. Patients who needed supplemental sedative premedication and those with major intraoperative complications (which might have independently affected recovery) were also excluded. Demographic and clinical data such as age, gender, BMI, ASA grade, type of surgery, and clinical history were collected after obtaining informed written consent. Baseline pre-operative anxiety before pre-medication was tested with a Visual Analog Scale for Anxiety (VAS-A), which ranged from 0 (no anxiety) to 10 (maximum anxiety).[18] Baseline measurements of heart rate, blood pressure, respiratory rate, and oxygen saturation were also taken. Patients subsequently received the premedication prescribed by the attending anesthesiologist. The dexmedetomidine group was administered intravenous dexmedetomidine, and the midazolam group was administered intravenous midazolam. Premedication and just prior to induction of anesthesia, anxiety and sedation were reassessed. Ramsay Sedation Scale was used to assess sedation, and the hemodynamic parameters were recorded at predefined intervals.[19] The doses and timing of administration were documented for each participant. Postoperatively, all the patients were given general anesthesia following institutional anesthetic protocol. Intraoperative variables including duration of anesthesia, duration of surgery, anesthetic requirements, hemodynamic events, and any adverse effects related to premedication were recorded. Patients were observed in the post-anesthesia care unit after surgery. Early postoperative recovery was assessed using the 15-item Quality of Recovery questionnaire (QoR-15) approximately 24 hours after surgery.[20] Postoperative pain, nausea and vomiting, requirement for rescue analgesia, time to eye opening, time to extubation and duration of recovery-room stay were also documented. Data were analyzed using SPSS version 26.0. The Shapiro–Wilk test was used to determine whether continuous variables were normally distributed, and they were reported as a mean ± standard deviation or a median with interquartile range as appropriate. Categorical variables were reported as frequencies and percentages. The dexmedetomidine and midazolam cohorts were compared using the independent-samples t-test for normally distributed continuous variables and the Mann–Whitney U test for non-normally distributed variables. Categorical variables were compared using the chi-square test and Fisher's exact test. The difference between the baseline anxiety score and the post-premedication anxiety score was analyzed between the two groups, and change in anxiety score from baseline was also assessed. As the major postoperative outcome, comparison was made between the scores of the QoR-15 at 24 hours. The following variables were stratified: age, sex, ASA status, and type of surgery. A two-sided p-value <0.05 was considered statistically significant, and 95% confidence intervals were reported.

The study included 110 patients, 55 patients per cohort. Mean age was 39.6 ± 10.8 years in the dexmedetomidine group and 40.8 ± 11.2 years in the midazolam group. There was no statistically significant difference between the two groups for age, sex, BMI, ASA physical status, type of surgery, surgery duration, or anesthesia duration (Table 1).

There were no differences in either baseline VAS-A or VAS-B scores between the dexmedetomidine and midazolam groups (p=0.472 and p=0.725, respectively). Following premedication, anxiety scores decreased to 2.8 ± 1.2 and 3.5 ± 1.3, respectively (p=0.004), with a significantly greater mean reduction in the dexmedetomidine group (p=0.002). Heart rate and blood pressure were also lower in the dexmedetomidine group (Table 2), while respiratory rate and oxygen saturation were similar.

Mean doses of dexmedetomidine and midazolam were 62.4 ± 8.7 µg and 2.1 ± 0.5 mg, respectively, and were similar for the interval between premedication and induction. Bradycardia was more common after dexmedetomidine, and respiratory depression was seen only in the midazolam group, but there was no significant difference in the incidence of adverse effects between groups (Table 3).

Dexmedetomidine patients required significantly less anesthesia (p<0.001). Intraoperative hypotension, bradycardia, time to eye opening, time to extubation, and PACU stay were not significantly different (Table 4).

The mean scores for the QoR-15 were significantly greater in the dexmedetomidine group than the midazolam group at 24 hours after surgery (p=0.003). There was also a significant between-group difference in physical comfort, psychological support, and emotional state, while there was no statistically significant difference in physical independence and the pain component of the QoR-15 (Table 5).

Postoperative pain scores were lower in patients receiving dexmedetomidine, and there were fewer instances of rescue pain medication needed 24 hours after surgery when compared with midazolam. Additionally, the total amount of rescue analgesic required was significantly reduced in the dexmedetomidine group, and there was no significant difference in the incidence of postoperative nausea and vomiting between the groups (Table 6).

Stratified analysis demonstrated that the reduction in preoperative anxiety was greater with dexmedetomidine in the majority of age, sex, ASA, and surgical subgroups. Statistically significant differences were observed in several strata, although the difference did not reach statistical significance in patients with ASA II status, those undergoing gynaecological surgery, and those undergoing ENT/other procedures (Table 7).

There was a significant (p<0.001) inverse correlation between the anxiety score change and the QoR-15 score at 24 h in the total population; the higher the change in anxiety score, the higher the score on the QoR-15 at 24 h. Similar associations were observed within both treatment cohorts (Table 8).

Table 1. Demographic and baseline clinical characteristics of study participants

Table 2. Preoperative anxiety, sedation, and hemodynamic parameters before and after premedication

Table 3. Premedication characteristics and adverse effects

Table 4. Intraoperative anesthetic and recovery characteristics

Table 5. Postoperative recovery outcomes at 24 hours

Table 6. Postoperative pain, nausea, vomiting and rescue analgesic requirement

Table 7. Stratified analysis of change in preoperative anxiety score

Table 8. Association of preoperative anxiety reduction with early quality of recovery

The present prospective cohort study showed that both dexmedetomidine and midazolam could relieve anxiety before anesthesia, but the effect of dexmedetomidine on VAS-A was more significant. Baseline anxiety was comparable between the groups, while post-premedication anxiety decreased from 6.4 ± 1.4 to 2.8 ± 1.2 with dexmedetomidine compared with a reduction from 6.2 ± 1.5 to 3.5 ± 1.3 with midazolam. The results indicate that dexmedetomidine had a significantly more pronounced early anxiolytic effect on the adult surgical patient population studied. Midazolam was observed to decrease anxiety in adults undergoing laparoscopic surgery in a randomized trial conducted in 2021, which showed that additional supportive elements to the administration of midazolam (hand-holding, conversation) led to further anxiety reduction, suggesting that non-pharmacological factors play a role in the reduction of perioperative anxiety.[21] The results are also in line with those of pediatric patients, although direct comparisons should be interpreted with some caution due to age differences and measurement of anxiety. A randomized study of oral midazolam vs. intranasal dexmedetomidine in children in 2021 revealed that in this group of children, the combination of the two drugs resulted in a more rapid attainment of adequate sedation than either agent alone when used for sedation. In 2021, a randomized study compared the use of oral midazolam with intranasal dexmedetomidine for sedation in children and reported that the combination of the two agents was associated with faster onset of adequate sedation compared to either agent alone. This supports the sedative and anxiolytic activity of dexmedetomidine but also indicates that its clinical effects depend on route, dose, and timing of administration.[22] The greater anxiety reduction observed with dexmedetomidine in our study may partly be related to its combined sedative, sympatholytic, and analgesic properties. A 2023 randomized trial by Guo et al., performed in patients undergoing video-assisted thoracoscopic lobectomy, confirmed this interpretation with better early QoR-15 scores and postoperative analgesia produced by dexmedetomidine combined with an erector spinae plane block. The investigators reported a clinically significant improvement in QoR-15 at 24 hours with the higher dexmedetomidine dose, although the difference was no longer evident at 48 and 72 hours.[23] The present study also revealed that patients receiving dexmedetomidine had a significantly higher QoR-15 score at 24 hours (127.6 ± 12.8 versus 119.8 ± 14.1). A large systematic review and Bayesian meta-analysis of 44 randomized trials of 5,904 surgical patients in 2024 confirmed this finding. Moderate-certainty evidence was found for dexmedetomidine being associated with an average improvement of around 9 points in recovery scores on the QoR-15. The amount of difference found in our study is thus in line with the clinically acceptable differences found in the general literature.[24] In our study, the benefit of early recovery was linked to fewer postoperative pain complaints and less requirement for rescue analgesics in the dexmedetomidine group. Recent studies on dexmedetomidine-containing analgesic strategies have yielded similar results. A randomized trial of dexmedetomidine as an adjunct to erector spinae plane block reported lower postoperative pain scores, reduced rescue analgesic consumption, and improved QoR-15 at 24 hours, particularly with the higher dexmedetomidine dose.[24] The results of a 2025 randomized trial in patients undergoing thoracoscopic surgery were similar: dexmedetomidine showed significantly higher QRS-15 scores, with a score of 127.1 ± 7.3 in the dexmedetomidine group versus 118.4 ± 9.3 in the control group on day 1. The improvements were most specifically linked to pain and physical comfort. The magnitude and direction of this difference are comparable to our findings, despite differences in surgical population and dexmedetomidine administration.[22] There is also evidence that this is helpful for early recovery in elderly patients who are having a total knee replacement. A recent randomized clinical trial revealed a six-point difference between the two groups, with the higher-dose dexmedetomidine group having a median QoR-15 score of 126 on postoperative day 1, versus 120 for the saline group. Although our study included younger adults and compared dexmedetomidine directly with midazolam, the similarly higher early QoR-15 scores suggest that the recovery benefit may extend across different surgical populations.[25] More recent evidence specifically addressing anxiety and QoR-15 is particularly relevant to our findings. In a randomized 2026 patient study conducted before modified radical mastectomy, intranasal dexmedetomidine effectively lowered both the level of perioperative anxiety and the QoR-15 scores at 24 and 48 hours. The 24-hour QoR-15 score was 120.11±6.90 with dexmedetomidine versus 111.27±7.14 in the control group. These results are highly similar to the observation in our study that dexmedetomidine may have a dual effect of decreasing perioperative anxiety and enhancing early patient-reported recovery.[26] However, not all recent evidence demonstrates superiority of dexmedetomidine over midazolam. In an adult randomized double-blind study in 2026 comparing dexmedetomidine to midazolam for elective laparoscopic cholecystectomy, no significant differences were observed in most clinical parameters, including ACTH level before induction of anesthesia, postoperative pain, anesthetic requirement, and hemodynamic parameters. Dexmedetomidine was numerically more likely to cause hypotension and bradycardia. These results suggest the differences between dexmedetomidine and midazolam may be related to the surgical population, dosage, route, and outcome measure, and offer a contrasting result to the increased anxiety reduction found in our population.[27] LIMITATIONS The study had several limitations. First, its prospective cohort design did not involve random allocation, and therefore selection bias and residual confounding related to the anesthesiologist's choice of premedication could not be completely excluded. Second, the study was conducted at a single tertiary-care hospital, which may limit the generalizability of the findings to other settings. Third, the sample size was relatively small, and the follow-up was limited to the early postoperative period, with QoR-15 assessed at 24 hours only. Variations in surgical procedures and anesthetic management may also have influenced postoperative recovery. Finally, anxiety was assessed using VAS-A, which is subjective and may be influenced by individual perception.

Dexmedetomidine premedication was associated with a greater reduction in preoperative anxiety and higher 24-hour QoR-15 scores compared with midazolam in patients undergoing general anesthesia. It was also associated with lower postoperative pain and rescue analgesic requirements. However, greater reductions in heart rate and blood pressure and more frequent bradycardia highlight the need for appropriate monitoring. These findings suggest potential benefits of dexmedetomidine for anxiety control and early recovery, while larger randomized studies are required to establish comparative effectiveness.