European Journal of Cardiovascular Medicine

Preoperative anxiety is a significant challenge in modern surgical practice, affecting an estimated 60-80% of surgical patients [1]. This psychological state is characterized by unpleasant tension, apprehension, and autonomic nervous system activation in anticipation of surgery [2]. The implications of preoperative anxiety extend far beyond mere patient discomfort, potentially influencing surgical outcomes, recovery trajectories, and overall healthcare experiences.

The physiological response to preoperative anxiety manifests through various mechanisms, including elevated cortisol levels, increased heart rate, and heightened blood pressure [3]. These stress-induced changes can complicate anesthetic management, increase postoperative pain, and potentially compromise immune function during the critical recovery period [4]. Furthermore, studies have demonstrated correlations between high preoperative anxiety levels and increased postoperative complications, extended hospital stays, and higher analgesic requirements [2,3].

In response to these challenges, the medical community has long recognized the importance of preoperative anxiolysis. Anxiolytic medications, particularly benzodiazepines, have become a cornerstone in preoperative management protocols [5]. These medications work by enhancing the effect of gamma-aminobutyric acid (GABA), the primary inhibitory neurotransmitter in the central nervous system, thereby reducing anxiety and promoting relaxation [6]. Common agents include midazolam, diazepam, and lorazepam, each with distinct pharmacokinetic profiles and clinical applications.

The selection of appropriate anxiolytic medications requires careful consideration of multiple factors, including the patient's age, comorbidities, the type of surgery, and the anesthetic plan [7]. While these medications can effectively reduce anxiety, their use must be balanced against potential side effects such as respiratory depression, paradoxical reactions, and prolonged recovery times. Additionally, the timing of administration is crucial, as it can affect both the medication's efficacy and the overall perioperative workflow [8].

Recent research has focused on evaluating the broader impact of preoperative anxiolysis on surgical outcomes and patient satisfaction. Studies have investigated various endpoints, including postoperative pain scores, recovery times, complications rates, and patient-reported experience measures [9]. Understanding these relationships is crucial for developing evidence-based protocols that optimize both clinical outcomes and patient experiences.

The increasing emphasis on patient-centered care has also highlighted the importance of measuring and addressing preoperative anxiety. Patient satisfaction, now recognized as a key quality indicator in healthcare delivery, is significantly influenced by the effectiveness of preoperative anxiety management [10]. This has led to growing interest in standardizing anxiety assessment tools and developing comprehensive approaches to preoperative anxiolysis that extend beyond pharmacological interventions.

This study aims to critically evaluate the current evidence regarding the effectiveness of preoperative anxiolytic medications, focusing on their impact on surgical outcomes and patient satisfaction. By examining both the direct anxiolytic effects and the broader implications for perioperative care, we seek to provide healthcare professionals with comprehensive insights to inform clinical decision-making and protocol development.

Aims and Objectives

The primary aim of this study was to evaluate the effectiveness of preoperative anxiolytic medications on surgical outcomes and patient satisfaction in adult patients undergoing elective surgery. The specific objectives included: assessment of the impact of standardized preoperative anxiolytic medication protocols on immediate postoperative outcomes; evaluation of patient satisfaction scores following preoperative anxiolysis; determination of the correlation between preoperative anxiety levels and postoperative pain scores; and identification of potential adverse effects associated with preoperative anxiolytic administration.

Study Design and Setting

This prospective, randomized, double-blind, placebo-controlled trial was conducted between September 2020 and September 2021 at Karpagam Faculty of Medical Sciences and Research, Othakalmandapam, Coimbatore.

Study Population

The study enrolled 120 adult patients scheduled for elective surgery under general anesthesia. The sample size was calculated using G*Power software (version 3.1.9.4), assuming an effect size of 0.3, α error of 0.05, and power of 0.80. Accounting for a potential dropout rate of 15%, the final sample size was determined to be 120 patients.

Inclusion and Exclusion Criteria

The study included patients aged 18-65 years, with American Society of Anesthesiologists (ASA) physical status I-III, who were scheduled for elective surgery with an expected duration of 1-3 hours. Patients were excluded if they had a history of psychiatric disorders, chronic anxiolytic or antidepressant medication use, substance abuse, pregnancy, emergency surgery, or known allergies to the study medications. Additionally, patients unable to comprehend the anxiety assessment tools or those unwilling to provide informed consent were excluded from the study.

Randomization and Blinding

Patients were randomized using computer-generated random numbers into two groups: the intervention group (n=60) and the control group (n=60). The randomization sequence was concealed using sequentially numbered, opaque, sealed envelopes. Both the patients and the healthcare providers directly involved in patient care were blinded to the group allocation. The study medications were prepared by the hospital pharmacy in identical-appearing syringes.

Intervention Protocol

The intervention group received Intravenous Midazolam 0.02-0.03 mg/kg 3-5 minutes before scheduled surgery. The control group received matching placebo solution. All patients underwent standard preoperative preparation according to institutional protocols. Baseline anxiety levels were assessed using the State-Trait Anxiety Inventory (STAI) and Visual Analog Scale for Anxiety (VAS-A) during the pre-anesthetic evaluation and immediately before the administration of the study medication.

Outcome Measures

The primary outcome measures included postoperative pain scores assessed using the Visual Analog Scale (VAS) at 2, 6, 12, and 24 hours post-surgery; patient satisfaction scores measured using a modified Patient Satisfaction Questionnaire (PSQ-18); and the incidence of postoperative complications within 48 hours. Secondary outcomes included time to discharge from the post-anesthetic care unit (PACU), total analgesic consumption in the first 24 hours, and the incidence of adverse effects related to anxiolytic medication.

Data Collection and Monitoring

Trained research assistants collected demographic data, surgical details, and outcome measures using standardized case report forms. Vital parameters were monitored continuously during the perioperative period. An independent Data Safety Monitoring Board (DSMB) reviewed safety data every three months throughout the study duration. Protocol deviations and adverse events were documented and reported according to institutional guidelines.

Statistical Analysis

Statistical analysis was performed using SPSS version 26.0 (IBM Corp., Armonk, NY). Continuous variables were expressed as mean ± standard deviation or median (interquartile range) based on the distribution of data. Categorical variables were expressed as frequencies and percentages. Between-group comparisons were performed using Student's t-test or Mann-Whitney U test for continuous variables and Chi-square or Fisher's exact test for categorical variables. A mixed-model repeated measures ANOVA was used to analyze changes in anxiety and pain scores over time. Multiple regression analysis was performed to identify predictors of patient satisfaction. Statistical significance was set at p<0.05, and all tests were two-tailed.

A total of 120 patients were enrolled and randomized equally into intervention (n=60) and control (n=60) groups. The baseline demographic and clinical characteristics were comparable between the groups. The mean age of participants was 44.8 ± 13.2 years in the intervention group and 45.3 ± 12.9 years in the control group (p=0.832). Female participants comprised 56.7% and 58.3% of the intervention and control groups, respectively (p=0.852). Body mass index and ASA physical status distribution were similar between groups (p=0.594 and p=0.928, respectively). The distribution of surgical procedures was balanced, with general surgery being the most common (40.0% vs 41.7%), followed by orthopedic (31.7% vs 30.0%) and gynecological procedures (28.3% vs 28.3%, p=0.946). Baseline anxiety levels measured by STAI (48.3 ± 8.7 vs 47.8 ± 8.9, p=0.754) and VAS-A scores (6.7 ± 1.8 vs 6.5 ± 1.7, p=0.524) were comparable between groups.

Analysis of primary outcomes revealed significantly lower postoperative pain scores in the intervention group across all time points. At 2 hours post-surgery, the mean VAS pain score was 3.8 ± 1.6 in the intervention group compared to 5.4 ± 1.8 in the control group (mean difference -1.6, 95% CI: -2.2 to -1.0, p<0.001). This significant difference persisted at 6 hours (3.2 ± 1.4 vs 4.6 ± 1.6), 12 hours (2.8 ± 1.3 vs 3.9 ± 1.5), and 24 hours (2.1 ± 1.2 vs 3.0 ± 1.3) post-surgery (all p<0.001). Pre-surgery STAI scores demonstrated marked improvement in the intervention group (34.8 ± 7.1) compared to the control group (44.9 ± 7.8), with a mean difference of -10.1 (95% CI: -12.7 to -7.5, p<0.001).

Secondary outcome measures showed significant advantages in the intervention group. The mean duration of PACU stay was shorter in the intervention group (42.6 ± 11.4 minutes vs 49.8 ± 13.2 minutes, p<0.001). Total analgesic consumption was significantly lower in the intervention group (median 11.5 mg, IQR 7.0-16.0) compared to the control group (median 17.5 mg, IQR 11.0-22.0, p<0.001). The length of hospital stay was reduced in the intervention group (2.6 ± 0.8 days vs 3.0 ± 1.0 days, p=0.014). Patient satisfaction scores were notably higher in the intervention group (8.2 ± 1.1 vs 7.1 ± 1.3, p<0.001). The requirement for rescue medication was significantly lower in the intervention group (20.0%) compared to the control group (38.3%, p=0.026).

The safety profile analysis revealed comparable rates of adverse events between groups. Post-operative nausea and vomiting occurred in 15.0% of intervention group patients compared to 16.7% in the control group (p=0.804). The intervention group showed a slightly higher incidence of excessive sedation (5.0% vs 1.7%, p=0.309), though this difference did not reach statistical significance. The overall complication rate was similar between groups (26.7% vs 21.7%, p=0.516).

Multiple regression analysis identified several significant predictors of patient satisfaction. IV midazolam use demonstrated the strongest positive association (β=0.465, 95% CI: 0.298 to 0.632, p<0.001), followed by age (β=0.118, 95% CI: 0.036 to 0.200, p=0.005). Baseline anxiety showed a significant negative correlation (β=-0.242, 95% CI: -0.370 to -0.114, p<0.001), while ASA status was inversely associated with satisfaction (β=-0.138, 95% CI: -0.256 to -0.020, p=0.022). The regression model explained 36.2% of the variance in patient satisfaction (adjusted R²=0.344, F=22.14, p<0.001).

Table 1: Baseline Demographic and Clinical Characteristics

Table 2: Primary Outcome Measures - Pain and Anxiety Scores

Table 3: Secondary Outcomes and Recovery Parameters

Table 4: Adverse Events and Complications

Table 5: Multiple Regression Analysis for Patient Satisfaction

This study demonstrates the significant impact of preoperative IV midazolam on surgical outcomes and patient satisfaction in elective surgical procedures. Our findings merit careful comparison with existing literature while considering both supporting and contrasting evidence.

Pain Control and Anxiety Reduction

The significant reduction in postoperative pain scores observed in our intervention group (mean difference -1.6, 95% CI: -2.2 to -1.0, p<0.001 at 2 hours) aligns with findings from the seminal work by Kain et al. [11], who studied 270 women undergoing hysterectomy and reported a 28% reduction in early postoperative pain scores (p<0.001) with preoperative midazolam. The improvement in anxiety scores (STAI reduction of 10.1 points, p<0.001) closely parallels results from Schmitt and Hamedani [12], who documented a mean STAI reduction of 9.8 points (95% CI: 8.2-11.4, p<0.001) in their prospective study of 185 surgical patients.

PACU Recovery and Resource Utilization

Our observation of reduced PACU duration (42.6 ± 11.4 vs 49.8 ± 13.2 minutes, p<0.001) supports findings by Vinik et al. [13], who reported a mean reduction of 8.4 minutes (95% CI: 6.2-10.6, p<0.001) in PACU stay among 234 patients receiving preoperative anxiolysis. However, our results contrast with those of Mijderwijk et al. [14], whose multicenter study of 322 patients found no significant difference in PACU duration (mean difference 2.8 minutes, p=0.234), possibly due to variations in discharge protocols and institutional practices.

Analgesic Requirements and Pain Management

The reduced analgesic consumption in our intervention group (median difference 6.0mg, p<0.001) reinforces the findings of Maurice-Szamburski et al. [15], who documented a 33% reduction in postoperative opioid requirements (95% CI: 25-41%, p<0.001) in their randomized trial of 280 patients. This relationship between preoperative anxiolysis and postoperative pain management was further validated in Gandhi's systematic review [16] of 23 randomized controlled trials involving 1,864 patients.

Safety Profile and Adverse Events

Our safety analysis showing comparable complication rates (26.7% vs 21.7%, p=0.516) aligns with the comprehensive safety data reported by Orser et al. [17] in their prospective cohort study of 445 patients, where no significant difference in adverse events was found between midazolam and control groups (RR 1.12, 95% CI: 0.89-1.41, p=0.324). The slightly higher incidence of sedation in our intervention group (5.0% vs 1.7%, p=0.309) falls within the expected range documented by Sneyd's international registry study [18] of 1,240 patients receiving preoperative midazolam.

Study Limitations and Future Directions

The primary limitations of our study include its single-center design and relatively modest sample size of 120 patients. While our findings demonstrate statistical significance, larger multicenter trials would be valuable for confirming these results across diverse populations and clinical settings. Additionally, future research should investigate optimal dosing regimens and timing of administration, particularly in specific patient subgroups.

This randomized controlled trial provides robust evidence supporting the efficacy of preoperative IV midazolam in improving surgical outcomes and patient satisfaction. The intervention demonstrated significant benefits in multiple domains: reduced postoperative pain (mean difference -1.6, p<0.001), decreased anxiety levels (STAI reduction of 10.1 points, p<0.001), shorter PACU stays (42.6 vs 49.8 minutes, p<0.001), and higher patient satisfaction scores (8.2 vs 7.1, p<0.001). The comparable safety profile between groups (complication rates 26.7% vs 21.7%, p=0.516) further supports the routine use of preoperative IV midazolam in suitable surgical candidates.

These findings have important clinical implications for perioperative care protocols. The demonstrated benefits in both objective outcomes and subjective patient experience measures suggest that standardized preoperative anxiolysis should be considered as part of comprehensive surgical care pathways. Future research directions should include investigation of patient-specific factors affecting treatment response, optimal timing of administration, and long-term outcomes assessment.

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