Sedation during gastrointestinal (GI) endoscopic procedures has become a cornerstone of modern diagnostic and therapeutic gastroenterology. Recent trends have shown a global increase in the number of endoscopic procedures performed. With this, there is also increased exploration for safe, effective, and patient-satisfactory sedation protocols. Currently, approximately 98% of all upper and lower gastrointestinal endoscopic procedures are conducted under some form of sedation. This demonstrates a shift in clinical protocol that now emphasizes patient comfort, cooperation, and procedural efficacy [1,2]. The pharmacological agents used for this procedure include propofol, an alkylphenol derivative that has been widely accepted because of its rapid onset, short duration of action, and good recovery characteristics. Propofol belongs to the sedative-hypnotic agent class of drugs that causes anesthesia by potentiating GABA-A receptor activity, resulting in rapid induction of anesthesia and smooth recovery [3,4]. Its pharmacokinetic properties facilitate rapid redistribution and clearance, which is advantageous in outpatient procedures (e.g., endoscopies) where early discharge is required. Its use as a single sedative is not without limitations because it does not have analgesic properties and can cause dose-dependent cardiopulmonary depression, requiring co-administration with other sedatives to maximize efficacy and safety [5]. To overcome this disadvantage, it has become common clinical practice to use adjunct drugs such as Fentanyl and Midazolam. Fentanyl, a potent opioid agonist, is synergistic with propofol to increase analgesia, decrease propofol consumption, and decrease the airway reflexes during upper gastrointestinal endoscopy [6]. Fentanyl has a rapid onset and short duration and is useful for short procedures, but its respiratory depressant actions need close monitoring [7]. Midazolam is a short-acting benzodiazepine with anxiolytic and amnestic properties that enhances sedation through synergism with propofol, which reduces its dose and increases tolerance to it [8]. The use of propofol in combination with Midazolam or Fentanyl is therefore not just synergistic, but has been designed to overcome the shortcomings of either drug while obtaining the advantage of their strengths [9,10]. In recent years, international task forces, such as the American Society of Anesthesiologists and gastroenterology societies, have issued guidance focused on balanced sedation techniques that are specific to the procedure and patient safety profile [11]. Deep sedation by anesthesiologists increases the level of comfort and ease of the procedure, but it also has resource and cost implications, particularly for high-volume centers. Therefore, evidence-based combinations of sedative agents that ensure safety, efficacy, and cost-effectiveness are essential [12]. Due to the paucity of data in India and the variability in patient demographics, nutritional status, pharmacogenetics, and institutional protocols, local validation of sedation regimens is mandated. The current study was designed to evaluate the Midazolam and Fentanyl Combination with Propofol for Sedation in Gastrointestinal Endoscopies in patients reporting to our tertiary care hospital.

This prospective, comparative observational study was conducted at the Department of Anaesthesiology in collaboration with the Department of Gastroenterology at Konaseema Institute of Medical Sciences and Research Foundation (KIMS&RF), Amalapuram, a tertiary care teaching hospital in Andhra Pradesh. For 15 months, from June 2023 to May 2025. Institutional Ethical approval was obtained after duly following the protocol for human research. Written informed consent was obtained from all the participants of the study after explaining the nature of the study and possible outcomes in the vernacular language. Based on the study duration and feasibility, a total of n=80 patients were included based on the available eligible cases during the study period. Inclusion Criteria 1. Patients scheduled to undergo diagnostic or therapeutic upper gastrointestinal endoscopic procedures under sedation. 2. Male and Female 3. Adults aged above 18 years 4. ASA Physical Status Class I or II 5. Patients who provided written informed consent Exclusion Criteria 1. Patients with severe cardiac, pulmonary, or renal disorders interfering with sedation or data collection 2. Patients with liver disorders 3. Patients with incomplete data 4. Emergency Endoscopies Sampling method: A convenience sampling technique was employed to enroll eligible patients based on the inclusion and exclusion criteria. Each patient was assessed preoperatively, and detailed history including age, gender, occupation, comorbidities, and relevant clinical features was documented. A thorough general and systemic examination was carried out before the procedure. Each patient was successively allocated into one group and the second group alternatively. Grouping and Drug Protocols Group M: Patients received midazolam 0.03 mg/kg intravenously, followed by propofol 0.5 mg/kg intravenously. Additional propofol boluses of 10–20 mg were administered as required for sedation. Group F: Patients received fentanyl 1 µg/kg intravenously, followed by propofol 0.5 mg/kg intravenously. Additional propofol boluses of 10–20 mg were administered as required for sedation. Sedation Procedure • Baseline parameters (heart rate, BP, respiratory rate, SpO₂) were recorded. • The sedative drug combinations were administered intravenously. • Sedation depth was adjusted based on clinical parameters and requirements for the procedure. • Oxygen was provided via nasal cannula at 2–4 L/min throughout the procedure. Parameters recorded were Demographic data: age, gender, BMI, duration of surgery. Sedation-related data: level of sedation; observer's assessment of awareness/sedation; the OAA/S bedside scale was scored from 1 to 5. It assesses a patient's response to voice and touch. The BIS translates a patient's EEG (brain waves) into a single number from 0 (flatline EEG) to 100 (fully awake) [13]. Time to induction, Recovery time, Side effects/adverse events. Patient and endoscopist satisfaction score. All variables were documented using a structured case record form. Statistical Analysis: All the available data were refined, segregated, and uploaded to an MS Excel spreadsheet and analyzed by EPI Info version 7.2.5 software. Continuous variables were represented as mean and standard deviation. Categorical variables were represented by frequency and percentages. Student's t-test was used to determine differences between mean values of two groups. Chi-square test was used to determine differences between two groups. Values of p (<0.05) were considered significant.

A total of n=80 patients were included in the study, divided equally into two groups of n=40 each. Table 1 presents the demographic and baseline profile of the participants included in the study. Analysis of the table shows that both groups were comparable with respect to baseline demographic and clinical characteristics. The mean age was 43.5 ± 10.2 years in Group M and 42.3 ± 9.8 years in Group F (p = 0.52). The distribution of gender, BMI, and ASA physical status was also comparable between the groups, with no statistically significant differences observed (p > 0.05 for all parameters). This indicates equal distribution of cases in the two arms of the study for comparison of results. Table 1: Demographic and Baseline Characteristics Parameter Group M Group F p-value Number of Patients 40 40 1.00 Age (Mean ± SD) 43.5 ± 10.2 years 42.3 ± 9.8 years 0.52 Gender (M/F) 24 / 16 22 / 18 0.64 BMI (kg/m²) 24.8 ± 2.6 25.1 ± 2.9 0.48 ASA Grade I / II 30 / 10 28 / 12 0.66 Analysis of sedation and procedure-related outcomes is depicted in Table 2. Analysis of the table indicates that significant differences were observed in several sedation-related outcomes. The time to achieve adequate sedation was significantly shorter in Group F than in Group M (2.1 ± 0.4 vs. 3.7 ± 0.6 minutes) and p < 0.001. Similarly, the recovery time was significantly shorter in Group F (28.9 ± 5.1 vs. 43.6 ± 7.4 minutes), p < 0.001. The mean total dose of propofol required was also significantly lower in Group F than in Group M (102.3 ± 14.2 vs. 118.5 ± 15.7 mg), p < 0.001. The lowest recorded BIS score was significantly lower in Group F (68.1 ± 3.8) compared with Group M (72.4 ± 4.5), p = 0.002, indicating a greater depth of sedation in the fentanyl group. The OAAS score at peak sedation was also slightly lower in Group F (1.9 ± 0.3 vs. 2.1 ± 0.4), p = 0.041. However, the procedure duration was comparable between the groups (12.1 ± 3.4 vs. 12.3 ± 3.2 minutes), p = 0.71. Table 2: Sedation and Procedure-Related Outcomes Parameter Group M Group F p-value Time to Sedation (min) 3.7 ± 0.6 2.1 ± 0.4 <0.001 Recovery Time (min) 43.6 ± 7.4 28.9 ± 5.1 <0.001 Total Propofol Used (mg) 118.5 ± 15.7 102.3 ± 14.2 <0.001 BIS Score (lowest recorded) 72.4 ± 4.5 68.1 ± 3.8 0.002 OAAS Score at peak sedation 2.1 ± 0.4 1.9 ± 0.3 0.041 Procedure Duration (min) 12.3 ± 3.2 12.1 ± 3.4 0.71 The evaluation of heart rate between the two groups showed that heart rate decreased during the initial period of the procedure in both groups, with a more pronounced reduction in Group F. In Group M, mean heart rate decreased from 84.2 bpm at baseline to 80.7 bpm at 10 minutes, followed by an increase to 83.0 bpm at the end of the procedure. In Group F, heart rate decreased from 85.0 bpm at baseline to 77.3 bpm at 10 minutes, subsequently increasing to 81.6 bpm at the end of the procedure (Figure 1). The comparison of oxygen saturation is presented in Table 3. The saturation levels were relatively well maintained in both groups throughout the procedure. In Group M, mean SpO₂ decreased from 98.1 ± 0.7% at baseline to 96.9 ± 1.5% at 10 minutes, followed by an increase to 97.1 ± 1.1% at the end of the procedure. In Group F, SpO₂ decreased from 97.9 ± 0.6% to 95.2 ± 1.6% at 10 minutes, with subsequent recovery to 96.0 ± 1.3%. The reduction appeared more pronounced in Group F, although the p values were not found to be significant. Table 3: Comparison of SpO₂ (%) between Groups Time Interval Group M Group F P value Baseline 98.1 ± 0.7 97.9 ± 0.6 0.298 5 minutes 97.5 ± 1.2 95.6 ± 1.4 0.149 10 minutes 96.9 ± 1.5 95.2 ± 1.6 0.086 End of Procedure 97.1 ± 1.1 96.0 ± 1.3 0.553 Regarding safety, oxygen desaturation below 90% occurred in 5% in Group M and 15% in Group F (p = 0.12). Hypotension, defined as a fall of more than 20% from baseline, occurred in 7.5% in Group M and 17.5% in Group F (p = 0.18). Bradycardia occurred in none of the patients in Group M and in 5% in Group F (p = 0.15). Nausea and vomiting were reported in 5% in Group M and 2.5% in Group F (p = 0.55). Although respiratory and haemodynamic adverse events were numerically more frequent in Group F, none of these differences reached statistical significance. Table 4: Adverse Events and Safety Profile Adverse Event Group M Group F p-value Oxygen Desaturation (<90%) 2 (5%) 6 (15%) 0.12 Hypotension (>20% drop) 3 (7.5%) 7 (17.5%) 0.18 Bradycardia (<50 bpm) 0 (0%) 2 (5%) 0.15 Nausea/Vomiting 2 (5%) 1 (2.5%) 0.55 Patient satisfaction scores were high in both groups, with a slightly higher score in Group F (9.0 ± 0.8 vs. 8.6 ± 1.1), although the difference was not statistically significant (p = 0.08). In contrast, endoscopist satisfaction was significantly higher with the fentanyl–propofol regimen (9.3 ± 0.6 vs. 8.2 ± 1.3; p = 0.004). Overall, the findings indicate that Fentanyl + Propofol provided faster onset of sedation, shorter recovery time, lower propofol requirement, and greater endoscopist satisfaction than Midazolam + Propofol, while both regimens demonstrated comparable procedure duration and an overall acceptable safety profile. Table 5: Satisfaction Scores Satisfaction Scale Group M Group F p-value Patient Satisfaction (1–10) 8.6 ± 1.1 9.0 ± 0.8 0.08 Endoscopist Satisfaction (1–10) 8.2 ± 1.3 9.3 ± 0.6 0.004

The present study was done to compare midazolam-propofol and fentanyl-propofol for sedation during gastrointestinal endoscopy. The allocation of cases in two groups was comparable with respect to age, sex, BMI and ASA physical status, reducing the likelihood that baseline differences influenced the sedation outcomes. This comparability is important because certain confounders can affect drug requirements, haemodynamic responses and recovery following procedural sedation. The results of this study showed that fentanyl-propofol produced a significantly faster onset of sedation as compared with midazolam-propofol. The mean times were 2.1 ± 0.4 and 3.7 ± 0.6 minutes, respectively (p < 0.001). Recovery was also considerably faster with fentanyl-propofol (28.9 ± 5.1 vs. 43.6 ± 7.4 minutes), and p values were found to be significant (Table 2). These findings are consistent with previous studies showing shorter induction and recovery times with propofol-opioid regimens compared with benzodiazepine-based sedation. Lera dos Santos et al. (11) in a similar study found that recovery time was 28.82 minutes with propofol-fentanyl combination and 44.13 minutes with midazolam-fentanyl combination during upper gastrointestinal endoscopy, with similar differences in sedation onset and discharge time. Correira et al. (14) in a randomized trial reported faster recovery with propofol-fentanyl than with midazolam-fentanyl. The shorter recovery observed with fentanyl-propofol appears to be particularly useful in day-care endoscopy, where rapid discharge and patient turnover are important factors. In our study, we found the fentanyl-propofol group required significantly less propofol than the midazolam-propofol group (102.3 ± 14.2 vs. 118.5 ± 15.7 mg) and p < 0.001(Table 2). This finding supports the fact that there is a synergistic effect of combining an opioid with propofol, allowing adequate sedation with a lower hypnotic dose. Previous studies in this field have similarly reported effective endoscopic sedation using relatively low doses of propofol when combined with opioid analgesia (15,16). Evaluation of sedation depth was greater with fentanyl-propofol, reflected by lower minimum BIS scores (68.1 ± 3.8 vs. 72.4 ± 4.5; p = 0.002) and lower OAAS scores at peak sedation (1.9 ± 0.3 vs. 2.1 ± 0.4; p = 0.041) (Table 2). Lera dos Santos et al. (11) demonstrated a higher proportion of cases with deep sedation with propofol-fentanyl using both BIS and OAAS assessment. The deeper sedation may explain the significantly higher endoscopist satisfaction in the present study (9.3 ± 0.6 vs. 8.2 ± 1.3; p = 0.004). This is probably because better patient immobility and tolerance facilitate endoscope manipulation. Patient satisfaction, however, was high in both groups and did not differ significantly (p = 0.08), suggesting that both techniques provided an acceptable level of procedural discomfort. Our results also indicate that both groups had decreased heart rate as well as systolic blood pressure during sedation. However, a greater decrease was observed in the fentanyl-propofol group. The lowest values occurred around 10 minutes and subsequently improved toward the end of the procedure. This pattern is consistent with the known cardiovascular effects of propofol and fentanyl. Despite the greater numerical reduction, clinically important bradycardia and hypotension were uncommon in our study groups. There was no significant difference in these adverse events between groups (Table 4). The SpO₂ declined to lower levels in the fentanyl-propofol group, particularly during the first 10 minutes. Oxygen desaturation below 90% occurred in 15% of patients in Group F compared with 5% in Group M, although the difference was not statistically significant (p = 0.12). Similar findings have been reported with opioid-containing sedation, where respiratory depression may be more pronounced but serious complications remain uncommon with appropriate monitoring and oxygen supplementation (13,15). Overall, fentanyl-propofol provided faster sedation, shorter recovery, lower propofol consumption and greater endoscopist satisfaction, while both regimens had comparable procedure duration and an acceptable safety profile. The greater sedation depth and the tendency toward more pronounced haemodynamic and respiratory changes with fentanyl indicate the need for careful monitoring, particularly during the early period after drug administration. The strengths of this study were the use of sedation scales, both BIS and OAAS, together with recovery time, propofol requirement, haemodynamic and respiratory parameters, adverse events, and patient and endoscopist satisfaction. The limitations included the relatively small sample size, single-centre design, and assessment of outcomes only during the procedure and immediate recovery period, which may limit the generalizability of the findings.

Within the limitations of the present study, it was found that fentanyl-propofol provided faster sedation, lower propofol requirements, and shorter recovery than midazolam-propofol during gastrointestinal endoscopy. Although transient oxygen desaturation and hypotension were more frequent with the fentanyl-propofol combination, no serious intervention was required. Both regimens were effective and safe in ASA I–II patients when appropriately monitored. Fentanyl-propofol also produced deeper sedation and led to greater endoscopist satisfaction scores. Although the patient satisfaction scores in both groups were comparable. Therefore, preliminary findings of this study suggest that fentanyl-propofol offers advantages in procedural efficiency and recovery during endoscopy. However, larger multicentric trials are needed to confirm these findings

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