European Journal of Cardiovascular Medicine

Bronchoscopy is an essential procedure in respiratory medicine, allowing direct visualization of the airways, diagnosis, and intervention in a range of pulmonary diseases. However, bronchoscopy is inherently uncomfortable and can provoke anxiety, discomfort, and even distress in patients, making sedation an important consideration for its successful performance. The choice of sedation can significantly impact both the patient's experience and the procedural outcomes, as inadequate sedation can lead to increased patient movement, discomfort, and reduced procedural tolerance, while overly deep sedation risks respiratory depression and other complications [1].

Sedation in Bronchoscopy
Various sedative agents are utilized to improve patient comfort during bronchoscopy. Midazolam, a benzodiazepine, has become one of the most frequently used drugs for sedation in these procedures. Its properties include anxiolytic, sedative, and amnesic effects, making it particularly suitable for bronchoscopy. Midazolam acts on the central nervous system by enhancing the inhibitory effects of gamma-aminobutyric acid (GABA), thereby inducing sedation and reducing anxiety [2]. However, midazolam alone may not always be sufficient for optimal sedation in all patients, especially those with higher baseline anxiety or those requiring prolonged procedures. In such cases, combining midazolam with other sedative agents may yield improved patient outcomes [3].

Combination Sedation with Fentanyl
Fentanyl, an opioid analgesic, is often combined with midazolam to enhance sedative efficacy. Fentanyl acts primarily by binding to opioid receptors, producing both analgesic and sedative effects that complement the anxiolytic properties of midazolam. Together, these drugs have a synergistic effect, allowing for a deeper and more stable level of sedation without requiring excessively high doses of either agent [4]. This combination aims to provide a balance between effective sedation and safety, minimizing the risk of respiratory depression while enhancing patient comfort [5].

Need for Comparative Evaluation
Despite the frequent use of both midazolam and fentanyl in clinical practice, the comparative benefits of midazolam alone versus a midazolam-fentanyl combination in bronchoscopy remain a subject of ongoing investigation. While previous studies have reported improved comfort and tolerability with the combined approach, the evidence is not entirely consistent, and patient responses to sedation can vary widely based on individual factors and procedural specifics [6-10]. Therefore, understanding the relative efficacy and safety of these two sedation protocols is crucial for optimizing patient care.

Objectives
The present study aims to evaluate patient-reported discomfort and procedural tolerability during bronchoscopy under two sedation protocols: midazolam alone and a combination of midazolam with fentanyl. By comparing these approaches, we seek to provide insights that may guide sedation choices in clinical settings, ultimately improving patient outcomes and procedural success.

Study Design

This study was designed as a prospective, randomized, controlled trial comparing the effects of two sedation protocols for patients undergoing bronchoscopy. The study included two groups: one receiving midazolam alone (Group M) and the other receiving a combination of midazolam and fentanyl (Group MF). The primary outcome was patient-reported discomfort, and secondary outcomes included procedural tolerability, sedation depth, and incidence of adverse events.

Study Population

Patients aged 18 to 70 years scheduled for elective bronchoscopy at our institution were eligible for inclusion. The study period was from Jan 2023 to sept 2024. Exclusion criteria included known hypersensitivity to benzodiazepines or opioids, significant respiratory depression, uncontrolled comorbidities (e.g., severe cardiovascular disease), pregnancy, and a history of substance abuse. All participants provided informed consent, and the study received approval from the institutional review board.

Sedation Protocols

1. Group M (Midazolam Alone): Patients received intravenous (IV) midazolam starting at 0.05 mg/kg, titrated by 1-2 mg every 5 minutes to reach a target RASS score of 0 to -3 (ranging from “alert and calm” to “moderate sedation”).
2. Group MF (Midazolam + Fentanyl): Patients received IV midazolam (starting dose of 0.03 mg/kg, titrated as needed) along with IV fentanyl (25–50 µg, with a cumulative dose limit of 100 µg). The target RASS score was also 0 to -3. Fentanyl doses were adjusted based on patient response to achieve stable sedation.

Sedation Depth and Tolerability Assessment

1. Sedation Depth: Sedation depth was assessed using the Richmond Agitation-Sedation Scale (RASS), recorded at baseline and every 5 minutes during the procedure. An optimal sedation level was defined as a RASS score of 0 to -3, where patients were calm, responsive, or showed moderate sedation.
2. Tolerability Assessment: Observer ratings of procedural tolerability were collected, using a scale from 1 (very poor) to 5 (excellent), reflecting ease of procedure completion and patient cooperation.

Statistical Analysis

The primary outcomes were mean RASS scores during the procedure and procedural tolerability ratings. RASS scores and tolerability ratings between the two groups were compared using Student’s t-test for continuous variables and the Chi-square test for categorical variables. A p-value < 0.05 was considered statistically significant.

Patient Demographics and Baseline Characteristics

A total of 100 patients were included in the study, with 50 patients in the midazolam-only group (Group M) and 50 in the midazolam-fentanyl group (Group MF). The mean age was similar between the groups, with no significant difference in gender distribution or baseline anxiety scores. Both groups were also comparable in terms of comorbidities, indicating a balanced distribution between the treatment arms.Table 1

Table 1 presents the demographic and baseline characteristics of the study population.

Sedation Depth (RASS Scores)

Patients in Group MF maintained more consistent sedation levels within the target RASS range of 0 to -3. The average RASS score for Group MF was -2.1 ± 0.8, compared to -1.3 ± 1.1 in Group M, indicating that the combination of midazolam and fentanyl achieved a deeper and more stable sedation level. This difference was statistically significant (p<0.001), supporting the efficacy of the combined protocol in achieving desired sedation depth. Table 2

Table 2: Mean RASS Scores during Bronchoscopy

Procedural Tolerability

Procedural tolerability was rated higher in Group MF, with 92% of procedures rated as "good" or "excellent" compared to 76% in Group M. Observers reported that patients in Group MF showed less movement and better cooperation, which facilitated easier bronchoscope maneuvering and procedure completion. Table 3

Table 3: Procedural Tolerability Ratings

Adverse Events

Both groups maintained stable hemodynamics, with no significant differences in blood pressure, heart rate, or oxygen saturation. Mild respiratory depression was observed in 6% of patients in Group MF, resolved with supplemental oxygen. No severe adverse events were recorded, supporting the safety of both sedation protocols when closely monitored. Table 4

Table 4: Adverse Events and Sedation Stability

Using the RASS scale allowed for a more precise assessment of sedation depth and stability in this study. The findings suggest that combining midazolam and fentanyl provides a stable, target-level sedation (RASS 0 to -3) and enhances procedural tolerability, with a minimal increase in adverse events. These results reinforce the value of using RASS as a reliable tool for sedation management in bronchoscopy, especially for procedures that benefit from deeper sedation levels.

The goal of this study was to evaluate the effectiveness of two sedation protocols—midazolam alone versus a combination of midazolam and fentanyl—in managing patient discomfort and procedural tolerability during bronchoscopy. By using the Richmond Agitation-Sedation Scale (RASS) to monitor sedation depth, this study provided a more objective assessment of sedation stability and patient comfort. Our results showed that the combined sedation approach (midazolam and fentanyl) yielded deeper and more stable sedation levels within the target RASS range of 0 to -3, and improved procedural tolerability, with minimal adverse events.

RASS as an Objective Measure of Sedation Depth

The RASS is a widely used, validated tool for assessing sedation levels, ranging from alertness to deep sedation, and allows clinicians to objectively measure and target specific sedation depths. In this study, the use of RASS provided a reliable means of achieving and maintaining the desired sedation depth for bronchoscopy. The average RASS score in the midazolam-fentanyl group (Group MF) was -2.1 ± 0.8, closer to the target range (0 to -3) compared to the midazolam-only group (Group M) with a mean RASS score of -1.3 ± 1.1. This difference indicates that fentanyl, when combined with midazolam, facilitates a deeper, more stable sedation, which is advantageous for procedures like bronchoscopy that can cause anxiety and discomfort due to the invasive nature of airway manipulation [1,2].

Compared to the subjective ratings of discomfort often used in studies (such as the VAS), RASS offers a more consistent, repeatable method for sedation assessment. This eliminates variability associated with subjective patient-reported scales and aligns sedation depth with clinical needs more precisely, allowing for a safer, standardized approach in procedural sedation.

Improved Tolerability with Combined Sedation

Our findings indicated that procedural tolerability was significantly higher in the midazolam-fentanyl group. Observers rated 92% of procedures in this group as "good" or "excellent," compared to 76% in the midazolam-only group. This improvement in tolerability likely stems from the enhanced sedation depth achieved in Group MF, as patients in deeper sedation levels tend to remain calmer and more cooperative. RASS scores closer to -2 to -3 suggest that patients are in a state where they can tolerate the procedure with minimal agitation or resistance, thus facilitating smoother bronchoscope navigation [3,4].

These findings are consistent with other studies that report improved procedural outcomes with combination sedation protocols. Fentanyl's analgesic properties complement midazolam's anxiolytic and sedative effects, addressing both pain and anxiety without requiring higher doses of either drug. This synergy reduces the risk of excessive sedation and adverse events, contributing to a safer, more tolerable procedure for both patients and clinicians [5].

Adverse Events and Safety

Despite the increased sedation depth in Group MF, the incidence of adverse events was minimal, with only 6% of patients experiencing mild respiratory depression, which was resolved with supplemental oxygen. There were no cases of severe hypotension, bradycardia, or prolonged respiratory depression, underscoring the safety of the midazolam-fentanyl combination when administered in a controlled setting and closely monitored. Previous studies have highlighted similar safety profiles, noting that careful titration of both drugs minimizes risks associated with deeper sedation [6].

RASS scoring also allows for rapid detection and management of potential over-sedation, as scores can be tracked continuously to ensure patients remain within the desired range. This approach provides an additional layer of safety compared to subjective discomfort scales, which may not detect changes in sedation depth promptly. Consequently, RASS enables clinicians to quickly intervene if patients deviate from the target sedation level, helping to prevent respiratory complications and other risks [7].

Comparison with Other Sedation Combinations and Methods

Alternative sedative combinations for bronchoscopy, including agents like dexmedetomidine and propofol, have also been explored in the literature. While these agents can achieve deep sedation, they often come with increased risks of hemodynamic instability and respiratory depression, especially when used in combination with opioids [8]. Dexmedetomidine, for example, is associated with bradycardia and hypotension, while propofol requires close monitoring for potential respiratory depression [9,10].

Our study demonstrates that a combination of midazolam and fentanyl achieves comparable or even superior sedation depth with fewer adverse effects, suggesting it may be a preferable choice for routine bronchoscopy in many patients. The combination of midazolam and fentanyl is particularly advantageous in settings where moderate sedation (RASS -1 to -3) is desired to balance patient comfort with procedural safety.

Study Strengths and Limitations

A key strength of this study was the use of RASS, which allowed for objective, standardized sedation monitoring and enabled clinicians to maintain sedation within a specified range. The prospective design and use of validated scoring criteria contributed to the reliability of our findings. The sample size was adequate for detecting significant differences in sedation depth and procedural tolerability between the two groups [11-13].

However, the study also had limitations. First, it was conducted in a single center, which may limit the generalizability of our findings. Additionally, while RASS provides an objective measure of sedation depth, it does not capture other aspects of patient experience, such as psychological comfort or satisfaction with sedation, which could be important for overall procedural tolerance. Future studies could benefit from a multimodal approach that combines RASS with subjective patient feedback for a more comprehensive assessment of sedation quality [14,15].

Clinical Implications

Our results suggest that the combination of midazolam and fentanyl, with sedation managed using the RASS, offers an effective protocol for bronchoscopy. The objective, real-time assessment of sedation depth with RASS enables clinicians to titrate sedatives to an optimal range, ensuring patients remain calm and cooperative while minimizing discomfort. Given the manageable safety profile observed in this study, the midazolam-fentanyl combination could be recommended as a standard approach for sedation in bronchoscopy [1,3].

In clinical practice, RASS could be integrated into bronchoscopy protocols, allowing healthcare providers to make data-driven decisions about sedation levels. This approach could improve procedural success, reduce patient anxiety, and minimize the risks of adverse events, ultimately enhancing the quality of care.

Future Research Directions

Future research should investigate the use of RASS in broader patient populations and explore other sedation combinations that may offer similar benefits. Comparative studies assessing patient satisfaction alongside RASS could provide insights into the patient-centered benefits of different sedation protocols. Additionally, multicenter trials may further validate the use of RASS and the midazolam-fentanyl combination across diverse clinical settings, ensuring that the findings are widely applicable. Cost-effectiveness analyses could also be valuable, particularly for resource-limited settings where efficient sedation protocols are needed.

This study demonstrates that a combination of midazolam and fentanyl significantly improves sedation stability and procedural tolerability during bronchoscopy compared to midazolam alone, as measured by the Richmond Agitation-Sedation Scale (RASS). The midazolam-fentanyl combination effectively maintained patients within the target sedation range (RASS 0 to -3), providing a deeper, more consistent level of sedation with minimal adverse events.

The findings support the use of RASS as an objective tool for monitoring sedation depth in bronchoscopy, allowing clinicians to achieve optimal sedation levels that balance patient comfort with safety. Given the favorable tolerability and safety profile, the midazolam-fentanyl combination can be recommended as a preferred sedation protocol for bronchoscopy, particularly in cases requiring moderate to deep sedation. Further research may validate these findings in larger, diverse patient populations, enhancing the generalizability of RASS-guided sedation management in clinical practice.

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