Safety and Efficacy of Alfentanil Compared to Sufentanil in Target- Controlled Infusion During Flexible Bronchoscopy: A Randomized Controlled Trial

Safety and Efficacy of Alfentanil Compared to Sufentanil in Target- Controlled Infusion During Flexible Bronchoscopy: A Randomized Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Safety and Efficacy of Alfentanil Compared to Sufentanil in Target- Controlled Infusion During Flexible Bronchoscopy: A Randomized Controlled Trial Jiayuan Niu, Dan Xu, Shuqian Liu, Dongnan Hou This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7843053/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Optimal anesthetic management during flexible bronchoscopy requires balancing sedation, safety, and procedural efficiency. Target-controlled infusion (TCI) systems offer precise drug delivery, but comparative data between opioids remain limited. This study compared the safety and efficacy of alfentanil versus sufentanil target-controlled infusion and conventional alfentanil bolus dosing during flexible bronchoscopy. Methods In this prospective, randomized, double-blind trial, 90 patients scheduled for bronchoscopy were enrolled and 1:1:1 assigned to alfentanil TCI (35 ng/mL, Group A), sufentanil TCI (0.2 ng/mL, Group S), or alfentanil bolus (5 µg/kg, Group M). Primary outcomes included hemodynamic stability and cough frequency. Secondary outcomes encompassed timing, respiratory complications, additional medication requirements, and procedural quality. Results Baseline demographics were well-balanced across groups (all P > 0.05). Cough incidence was significantly lower in both alfentanil groups compared to sufentanil TCI (Group A: median 1 [IQR 1-1.25]; Group M: median 1 [IQR 1–2] versus Group S: median 2 [IQR 1–3]; P = 0.006). Hemodynamic parameters showed time-dependent differences between groups, with significant variations in heart rate and diastolic blood pressure at several time points, though all values remained within clinically acceptable ranges. Induction time was significantly shorter with alfentanil TCI versus other groups (Group A: 2 [ 2 – 3 ] minutes versus Group S and M: 3 [ 2 – 4 ] and 3 [ 2 – 3 ] minutes, respectively; P < 0.001). Awakening time demonstrated marked differences, with alfentanil bolus providing the fastest recovery (Group M: 7.5 [ 5 – 10 ] minutes versus Group A: 10 [8.75-12] minutes versus Group S: 19 [14.25-22] minutes; P < 0.001). No significant differences were observed in respiratory depression rates, additional propofol needs, or bronchoscopist satisfaction scores between groups. Conclusions Alfentanil regimens provided superior cough suppression compared to sufentanil. Alfentanil TCI offered the fastest induction, while bolus dosing enabled the quickest recovery. Both demonstrated favorable safety, supporting alfentanil as the preferred opioid for flexible bronchoscopy, with regimen choice guided by clinical priorities. Trial Registration This trial was retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2400089901) on September 19, 2024. Target-controlled infusion alfentanil sufentanil flexible bronchoscopy randomized controlled trial Figures Figure 1 Figure 2 Background Flexible bronchoscopy (FB) represents one of the most essential diagnostic and therapeutic modalities in contemporary pulmonary medicine, enabling direct visualization and sampling of the tracheobronchial tree with relatively low morbidity [ 1 – 2 ]. However, the procedure involves significant patient discomfort due to laryngeal stimulation, cough reflex activation, and psychological distress, necessitating optimal anesthetic management to ensure patient tolerance while maintaining safety [ 3 – 4 ]. The evolution of procedural sedation for bronchoscopy has progressed from simple topical anesthesia to multimodal approaches incorporating systemic sedatives and analgesics [ 5 ]. Current guidelines recommend combination protocols utilizing benzodiazepines, propofol, and opioid analgesics to achieve adequate sedation depth while preserving respiratory drive and hemodynamic stability [ 6 – 7 ]. Among opioid options, alfentanil and sufentanil have emerged as preferred agents due to their favorable pharmacokinetic profiles, though comparative efficacy data remain limited. Alfentanil, a rapid-onset, short-duration synthetic fentanyl analog, exhibits pharmacological advantages including faster equilibration between plasma and effect-site concentrations, predictable dose-response relationships, and minimal accumulation with repeated dosing [ 8 ]. These properties make alfentanil particularly suitable for procedures requiring precise titration and rapid recovery. Conversely, sufentanil offers superior potency [approximately 5–10 fold greater than alfentanil] and potentially enhanced analgesic efficacy, though with correspondingly longer context-sensitive half-life [ 9 ]. Target-controlled infusion (TCI) technology represents a significant advancement in anesthetic drug delivery, utilizing pharmacokinetic modeling to achieve and maintain predetermined plasma or effect-site concentrations [ 10 ]. TCI systems offer theoretical advantages over traditional bolus dosing, including reduced inter-patient variability, improved titration precision, and enhanced recovery predictability [ 7 , 11 ]. However, the optimal opioid selection and delivery method for bronchoscopic procedures remains undefined. Previous investigations comparing opioid agents during bronchoscopy have yielded inconsistent results, often limited by small sample sizes, heterogeneous protocols, and the lack of standardized outcome measures [ 12 – 14 ]. Furthermore, direct comparisons between TCI and conventional bolus dosing regimens are scarce, limiting evidence-based decision-making in clinical practice. Therefore, this prospective, randomized, controlled study was designed to comprehensively compare the safety and efficacy of alfentanil versus sufentanil target-controlled infusion and conventional alfentanil bolus administration during flexible bronchoscopy, with particular attention to procedural comfort, hemodynamic stability, and recovery characteristics. Methods Study Design and Ethics This prospective, randomized, double-blind, controlled clinical trial was conducted from February 2022 to March 2023 at the Second Affiliated Hospital of Dalian Medical University, following approval by the institutional review board ([Ethics Review No. 135 of 2023]) and registration with the Chinese Clinical Trial Registry ([ChiCTR2400089901]). The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from all participants prior to enrollment. Participants Adult patients (aged 18-75 years) scheduled for elective diagnostic or therapeutic flexible bronchoscopy were eligible for inclusion. Inclusion criteria comprised: American Society of Anesthesiologists (ASA) physical status I-III, body mass index (BMI) < 28 kg/m², and ability to provide informed consent. Exclusion criteria included: known hypersensitivity to study medications, severe cardiovascular disease (ejection fraction < 40%, unstable angina, recent myocardial infarction), significant respiratory compromise (baseline SpO₂ < 90% on room air), hepatic or renal impairment, pregnancy or lactation, psychiatric disorders precluding cooperation, and emergency procedures. Randomization and Blinding Eligible patients were randomly allocated using computer-generated randomization sequences in sealed opaque envelopes to one of three treatment groups: Group A (alfentanil TCI, target concentration 35 ng/mL), Group S (sufentanil TCI, target concentration 0.2 ng/mL), or Group M (alfentanil intravenous bolus, 5 μg/kg). Randomization was stratified by ASA status and procedure type (diagnostic versus therapeutic). Study medications were prepared by an independent pharmacist not involved in patient care or data collection. Patients remained blinded (single-blinded) to treatment allocation throughout the study period. Anesthetic Protocol All patients underwent standardized preoperative assessment, including medical history, physical examination, and laboratory investigations as clinically indicated. Baseline vital signs were recorded, and intravenous access was established using an 18-gauge peripheral cannula. Continuous monitoring included electrocardiography, non-invasive blood pressure, pulse oximetry, and capnography when clinically appropriate. Pre-medication : All patients received midazolam 0.02 mg/kg intravenously 10 minutes prior to procedure initiation. Induction : Standardized co-induction was performed using remazolam 0.1 mg/kg intravenously across all groups, followed by study drug administration according to randomization: - Group A: Alfentanil TCI initiated at target plasma concentration 35 ng/mL - Group S: Sufentanil TCI initiated at target plasma concentration 0.2 ng/mL - Group M: Alfentanil bolus 5 μg/kg administered over 2 minutes TCI systems utilized validated pharmacokinetic models (Maitre model for alfentanil, Gepts model for sufentanil) with plasma targeting mode. Maintenance : Propofol boluses (0.5 mg/kg) were administered as needed to maintain adequate sedation depth, defined by Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) score 2-3. Target-controlled infusions were maintained throughout the procedure without adjustment unless clinically contraindicated. Topical Anesthesia : Standardized topical lidocaine (1%, maximum 7 mg/kg) was applied to the nasal passages, oropharynx, and vocal cords as per institutional protocol. Outcome Measures Primary Outcomes : 1. Hemodynamic stability assessed by heart rate, blood pressure, mean arterial pressure (MAP), and oxygen saturation (SpO₂) measured at predefined timepoints: T0 (baseline), Ta (pre-procedure), T1 (post-lidocaine application), T2 (bronchoscope passage through glottis), T3 (bronchoscope at carina) 2. Cough frequency during procedure (assessed by independent observer using standardized scale) Secondary Outcomes : 1. Timing parameters: induction time (drug administration to adequate sedation), procedure duration, awakening time (procedure end to spontaneous eye opening), and total sedation time. 2. Respiratory complications: incidence of respiratory depression, requirement for manual ventilation or airway intervention, and chokes requiring intervention. 3. Additional medication requirements: number and dose of propofol. 4. Procedural quality: bronchoscopist satisfaction score. 5. Recovery characteristics: post-procedure adverse events. Statistical Analysis The sample size calculation was based on previous studies suggesting a 30% reduction in cough incidence as clinically significant [15]. Assuming α = 0.05, β = 0.20, and a 15% dropout rate, 30 patients per group were required to detect this difference with adequate power. Statistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Normality of continuous variables was assessed using Shapiro-Wilk tests. Normally distributed data are presented as mean ± standard deviation and compared using one-way ANOVA with post-hoc Tukey tests. Non-normally distributed data are presented as median (interquartile range) and analyzed using Kruskal-Wallis tests with pairwise Mann-Whitney U comparisons. Categorical variables are expressed as frequencies and percentages, compared using χ² or Fisher’s exact tests as appropriate. Multiple comparisons were adjusted using Bonferroni correction where applicable. Statistical significance was defined as P < 0.05 (two-tailed). All analyses were performed on an intention-to-treat basis with sensitivity analyses on per-protocol populations. CONSORT Statement Our study adheres to the CONSORT guidelines for reporting randomized controlled trials. A completed CONSORT 2025 checklist is provided as an additional file to facilitate full evaluation and utilization of our methodology. Results Participant Flow and Baseline Characteristics From April to September 2023, 98 patients were initially screened for eligibility. Five individuals declined to provide informed consent and were excluded, while two procedures were terminated due to intraoperative bleeding, and one case required conversion to a specialized treatment, leading to exclusion. Consequently, 90 patients were successfully enrolled and randomized into three groups of 30 each. All randomized patients completed the study without loss to follow-up or significant protocol deviations (Fig. 1 ). Baseline demographic and clinical characteristics were well-balanced across treatment groups (Table 1 ). Mean age was 62.9 ± 7.7, 62.7 ± 7.5, and 63.3 ± 9.1 years for Groups A, S, and M, respectively (P = 0.959). Sex distribution, BMI, ASA classification, and Modified Mallampati scores showed no significant inter-group differences (all P > 0.05), confirming successful randomization. Table 1 Demographic and baseline characteristics by treatment group. Data are presented as mean ± standard deviation or n (%). P-values represent comparisons across all three groups. Characteristic Group A Alfentanil TCI (n = 30) Group S Sufentanil TCI (n = 30) Group M Alfentanil Bolus (n = 30) P-value Age (years), mean ± SD 62.93 ± 7.67 62.70 ± 7.49 63.30 ± 9.09 0.959 Sex, n (%) Male 19 (63.3%) 23 (76.7%) 20 (66.7%) 0.510 Female 11 (36.7%) 7 (23.3%) 10 (33.3%) 0.510 BMI (kg/m²), mean ± SD 22.68 ± 2.49 22.69 ± 2.57 22.62 ± 2.55 0.993 ASA classification, n (%) Class II 24 (80.0%) 23 (76.7%) 19 (63.3%) 0.148 Class III 6 (20.0%) 7 (23.3%) 11 (36.7%) 0.148 Modified Mallampati Score, n (%) Grade I 18 (60.0%) 20 (66.7%) 15 (50.0%) 0.437 Grade II 12 (40.0%) 10 (33.3%) 15 (50.0%) 0.437 Primary Outcomes Hemodynamic Stability All three anesthetic regimens maintained acceptable hemodynamic stability throughout the procedure (Fig. 2 ; Supplementary Table 1). While heart rate, blood pressure, mean arterial pressure, and oxygen saturation showed generally similar patterns across groups with expected responses to procedural stimulation, some time-dependent differences were observed. Heart rate showed significant variations between groups at post-induction and later time points, and diastolic blood pressure demonstrated differences during the procedural period. However, all hemodynamic parameters remained within clinically acceptable ranges throughout the study period. All patients maintained SpO₂ levels above 86% without requiring supplemental oxygen beyond standard care. Cough Incidence : Significant differences were observed in procedural cough frequency (Table 2 ). Both alfentanil groups demonstrated superior cough suppression compared to sufentanil TCI (Group A: 1 [1-1.25] episodes; Group M: 1 [ 1 – 2 ] episodes versus Group S: 2 [ 1 – 3 ] episodes; P = 0.006). Post-hoc analysis revealed statistically significant differences between Group S and both alfentanil groups (P 0.05). Table 2 Primary outcome measures by treatment group. Data are presented as median (interquartile range) or n (%). Asterisk (*) indicates statistical significance (P < 0.05). T0 (baseline), Ta (pre-procedure), T1 (post-lidocaine), T2 (scope through glottis), T3 (scope at carina). Primary Outcome Measure Group A Alfentanil TCI (n = 30) Group S Sufentanil TCI (n = 30) Group M Alfentanil Bolus (n = 30) P-value Incidence of cough median (IQR) 1 (1, 1.25) 2 (1, 3) 1 (1, 2) 0.006* Heart rate : T0 - Ta - T1 - T2 - T3 median (IQR) 83 (78, 93) 90 (85, 97) 96 (89, 105) 102 (88, 108) 98 (87, 102) 83 (74, 95) 92 (84, 99) 96 (80, 104) 93 (83, 103) 88 (82, 98) 80 (75, 88) 84 (74, 89) 86 (76, 93) 88 (79, 96) 92 (80, 97) 0.588 0.010* 0.194 0.032* 0.027* Systolic blood pressure : T0 - Ta - T1 - T2 - T3 median (IQR) 134 (122, 146) 118 (107, 127) 122 (107, 142) 126 (103, 139) 123 (104, 139) 131 (122, 138) 116 (105, 124) 123 (100, 139) 115 (103, 136) 114 (105, 138) 136 (122, 150) 118 (105, 128) 110 (99, 126) 121 (108, 134) 115 (105, 135) 0.474 0.551 0.057 0.530 0.176 Diastolic blood pressure : T0 - Ta - T1 - T2 - T3 median (IQR) 82 (72, 86) 74 (65, 85) 83 (68, 94) 76 (69, 92) 75 (69, 89) 80 (72, 86) 70 (59, 76) 72 (64, 83) 74 (66, 81) 72 (65, 81) 82 (73, 89) 71 (64, 75) 67 (63, 78) 72 (66, 77) 70 (64, 76) 0.437 0.245 0.002* 0.085 0.018* Mean arterial pressure : T0 - Ta - T1 - T2 - T3 median (IQR) 99 (89, 110) 87 (79, 104) 94 (83, 110) 90 (81, 111) 90 (82, 105) 95 (90, 103) 86 (76, 91) 86 (78, 101) 88 (77, 96) 87 (77, 96) 100 (92, 109) 87 (79, 93) 81 (72, 96) 90 (83, 97) 90 (77, 94) 0.615 0.889 0.001* 0.629 0.283 Peripheral oxygen saturation : T0 - Ta - T1 - T2 - T3 median (IQR) 98 (98, 99) 98 (96, 99) 95 (90, 97) 94 (91, 97) 94 (91, 96) 98 (97, 99) 98 (95, 99) 96 (93, 99) 94 (90, 96) 94 (90, 97) 98 (96, 100) 99 (98, 100) 97 (91, 98) 94 (89, 98) 93 (89, 97) 0.707 0.064 0.038* 0.787 0.847 Secondary Outcomes Timing Parameters : Marked differences were observed in procedural timing (Table 3 ; Supplementary Table 1). Induction time was significantly shorter with alfentanil TCI compared to other groups (Group A: 2 [ 2 – 3 ] minutes versus Group S: 3 [ 3 – 4 ] minutes and Group M: 3 [ 2 – 3 ] minutes; P < 0.001). Most notably, awakening time demonstrated substantial variation, with alfentanil bolus providing the fastest recovery (Group M: 7.5 [ 5 – 10 ] minutes versus Group A: 10 [8.75-12] minutes versus Group S: 19 [14.25-22] minutes; P < 0.001), representing a 2.5-fold difference between fastest and slowest recovery regimens. Table 3 Secondary outcome measures by treatment group. Data are presented as median (interquartile range). Asterisk (*) indicates statistical significance (P < 0.05). Secondary Outcome Measure Group A Alfentanil TCI (n = 30) Group S Sufentanil TCI (n = 30) Group M Alfentanil Bolus (n = 30) P-value Timing parameters Induction time (min) median (IQR) 2 (2, 3) 3 (3, 4) 3 (2, 3) < 0.001* Procedure duration (min) median (IQR) 11 (9, 14.25) 11.5 (9.75, 14) 10.5 (8.75, 15) 0.816 Awakening time (min) median (IQR) 10 (8.75, 12) 19 (14.25, 22) 7.5 (5, 10) < 0.001* Total sedation time (min) median (IQR) 14 (11.75, 17) 15 (12.75, 17) 14.5 (11.7, 17.25) 0.401 Respiratory complications Respiratory depression incidence n (%) 19 (63.3%) 23 (76.7%) 22 (73.3%) 0.621 Manual adjustment for respiratory depression median (IQR) 1 (0, 2) 1 (0, 2.25) 1 (0, 3) 0.539 Chokes requiring intervention median (IQR) 1 (0, 1) 1 (1, 2) 1 (0, 1.25) 0.056 Additional medication requirements Number of additional propofol median (IQR) 1.5 (1, 2) 2 (1, 3) 1 (1, 3) 0.642 Total additional propofol dose (mg) median (IQR) 55 (30, 82.5) 60 (40, 110) 40 (30, 92.5) 0.533 Procedural quality Bronchoscopist satisfaction score median (IQR) 4 (3, 5) 3 (2, 4) 3 (3, 3) 0.060 Respiratory Safety : Respiratory depression rates were comparable across groups (Group A: 63.3%, Group S: 76.7%, Group M: 73.3%; P = 0.621). Importantly, all episodes were mild and responded to simple interventions (tactile stimulation, jaw thrust) without requiring positive pressure ventilation or reversal agents. No significant differences were observed in manual airway intervention requirements or supplemental oxygen needs. Medication Requirements Total propofol consumption and rescue medication needs showed no significant inter-group differences (P > 0.05). Additional propofol doses were required 1.5 [ 1 – 2 ], 2 [ 1 – 3 ], and 1 [ 1 – 3 ] times, and the total doses administered were 55 [30–82.5] mg, 60 [40–110] mg, and 40 [30–92.5] mg for Groups A, S, and M, respectively (P = 0.642 and P = 0.533). Procedural Quality Bronchoscopist satisfaction scores were consistently high across all groups without significant differences. Adverse Events No serious adverse events related to study interventions were observed. Minor adverse events included transient hypotension (n = 3), brief oxygen desaturation (n = 5), and post-procedure nausea (n = 2), distributed evenly across groups. No emergency interventions, procedure terminations, or prolonged recovery complications occurred. Discussion This randomized controlled trial provides comprehensive comparative evidence regarding opioid selection and delivery methods for flexible bronchoscopy sedation. The principal findings demonstrate that alfentanil-based regimens, regardless of delivery method, offer superior cough suppression compared to sufentanil TCI while maintaining equivalent safety profiles. Additionally, significant differences in procedural timing favor alfentanil TCI for rapid induction and alfentanil bolus for expedited recovery. Clinical Implications of Cough Control The observed superior antitussive effect of alfentanil represents a clinically meaningful finding with direct procedural implications. Cough suppression during bronchoscopy is essential for optimal visualization, adequate sampling, and procedural safety [ 15 – 16 ]. Excessive coughing can compromise diagnostic yield, increase procedural duration, elevate aspiration risk, and contribute to patient discomfort and procedure-related anxiety [ 15 ]. The statistically significant reduction in cough episodes with alfentanil (effect size Cohen’s d = -0.95, representing moderate-to-large clinical effect) suggests meaningful improvement in procedural conditions. The mechanism underlying differential antitussive efficacy likely relates to pharmacokinetic and receptor binding characteristics. Alfentanil’s rapid onset and high µ-opioid receptor selectivity may provide more effective cough reflex suppression at the medullary level compared to sufentanil’s more gradual onset profile, despite the latter’s higher potency [ 17 – 18 ]. These findings align with previous investigations suggesting alfentanil’s superior antitussive properties in bronchoscopic applications [ 19 ]. Timing Considerations and Clinical Workflow The dramatic differences observed in induction and recovery times carry substantial implications for clinical workflow and resource utilization. Alfentanil TCI’s faster induction (33% time reduction) facilitates procedure scheduling efficiency [ 20 ] and reduces patient anxiety [ 19 ] associated with prolonged onset periods. More importantly, the 2.5-fold difference in awakening times between regimens directly impacts recovery bay utilization [ 18 ], nursing requirements [ 21 ], and overall procedural throughput [ 22 ]. The prolonged recovery associated with sufentanil TCI (median 19 vs 7.5 minutes for alfentanil bolus) likely reflects the drug’s longer context-sensitive half-life and higher lipophilicity, resulting in tissue redistribution and accumulation [ 23 – 24 ]. This finding challenges the common assumption that TCI systems uniformly provide predictable recovery profiles [ 25 – 26 ], emphasizing the continued importance of drug selection over delivery method sophistication. Safety Profile and Hemodynamic Stability The absence of significant hemodynamic differences across all regimens provides reassuring evidence regarding cardiovascular safety [ 27 ]. All three approaches demonstrated expected physiological responses to bronchoscopic stimulation without clinically significant blood pressure fluctuations, arrhythmias, or desaturation events. The comparable respiratory depression rates, while numerically high, reflect the sensitive definition employed (any decrease in respiratory rate or oxygen saturation) rather than clinically concerning events, as evidenced by the lack of intervention requirements [ 28 ]. These safety findings support the clinical viability of all three regimens for routine bronchoscopic procedures, with selection primarily driven by procedural priorities rather than safety concerns. The maintained SpO₂ levels above 86% across all groups exceed accepted thresholds for procedural sedation, while the absence of serious adverse events reinforces the appropriateness of current dosing protocols. Target-Controlled Infusion Considerations The mixed results regarding TCI advantages warrant careful interpretation. While alfentanil TCI provided fastest induction [ 10 ], it did not demonstrate superiority in recovery parameters compared to conventional bolus dosing. This finding suggests that TCI benefits may be drug-specific rather than universally applicable across all opioid agents [ 29 ]. The precise concentration control offered by TCI systems may be most advantageous for drugs with narrow therapeutic windows or unpredictable pharmacokinetic profiles, which may not apply to alfentanil given its favorable characteristics. Furthermore, the economic implications of TCI systems, including equipment costs, training requirements, and technical complexity, must be balanced against demonstrated clinical benefits [ 30 ]. The current results suggest that conventional bolus dosing may remain appropriate for many bronchoscopic applications, particularly when rapid recovery is prioritized. Study Limitations First, the single-center design may limit generalizability to different patient populations or practice environments. Second, the relatively small sample size, while adequately powered for primary endpoints, may have limited ability to detect rare adverse events or subtle differences in secondary outcomes. Third, the study population excluded high-risk patients, and results may not apply to critically ill or severely compromised individuals. The use of estimated rather than measured drug concentrations in plasma represents another limitation, though this reflects standard clinical practice where TCI systems rely on pharmacokinetic modeling rather than real-time drug level monitoring. Finally, the absence of long-term follow-up prevents assessment of delayed complications or patient satisfaction beyond the immediate recovery period. Clinical Recommendations Based on these findings, we recommend alfentanil over sufentanil for flexible bronchoscopy sedation due to superior cough control and more favorable timing profiles. The choice between TCI and bolus delivery should be guided by specific procedural priorities: TCI for situations requiring rapid onset (urgent procedures, anxious patients), and bolus dosing when expedited recovery is paramount (outpatient settings, high-volume practices, limited recovery resources). These recommendations align with contemporary trends toward personalized perioperative care, where anesthetic selection is tailored to individual patient characteristics and procedural requirements rather than utilizing universal protocols [ 31 – 33 ]. Future investigations should explore patient-specific factors that might predict optimal anesthetic selection and evaluate the cost-effectiveness of different regimens across diverse healthcare settings. Conclusions This randomized controlled trial demonstrates that alfentanil-based sedation regimens provide superior cough control compared to sufentanil TCI during flexible bronchoscopy while maintaining equivalent safety profiles. Alfentanil TCI offers fastest induction, while conventional alfentanil bolus dosing enables most rapid recovery. The choice between alfentanil delivery methods should be individualized based on specific clinical priorities and procedural requirements. These findings provide evidence-based guidance for anesthetic selection in bronchoscopic procedures and support alfentanil as the preferred opioid agent for this indication. The substantial differences in recovery times highlight the continued importance of drug selection over delivery method sophistication in achieving optimal procedural outcomes. Abbreviations TCI Target-Controlled Infusion FB Flexible Bronchoscopy ASA American Society of Anesthesiologists BMI Body Mass Index MAP Mean Arterial Pressure SpO₂ Oxygen Saturation MOAA/S Modified Observer’s Assessment of Alertness/Sedation IRB Institutional Review Board IQR Interquartile Range SD Standard Deviation Declarations Ethics approval and consent to participate This prospective, randomized, double-blind, controlled clinical trial was conducted with the approval of the institutional review board ([Ethics Review No. 135 of 2023]) by Second Affiliated Hospital, Dalian Medical University, and registration with the Chinese Clinical Trial Registry ([ChiCTR2400089901]). The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from all participants prior to enrollment, ensuring voluntary participation and the protection of patient rights throughout the study. Consent for publication All participants provided written informed consent for the publication of this study’s data, analyses, and findings. The consent included permission to publish anonymized data in scientific journals and conference presentations, ensuring individuals cannot be identified from any published material. This consent was obtained prior to participation and was documented systematically in accordance with institutional and ethical standards. Data availability statement The data supporting the findings of this study are available in Supplementary Table 1, which is provided with this manuscript. Competing interests The authors declare that they have no competing interests. Funding None. Author contribution statement [DH, JN, DX]: Conceptualization, methodology, investigation, writing—original draft preparation. [JN, DX, SL, DH]: Data curation, formal analysis, writing—review and editing. All authors approved the final manuscript. 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Clin Pharmacokinet. 1996;31(4):275–292. doi:10.2165/00003088-199631040-00004. Ou Y, Feng M, Hu B, Dong Y. The impact of alfentanil supplementation on the sedation of bronchoscopy: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2022;101(31):e27401. doi:10.1097/MD.0000000000027401. Hsieh CH, Lin TY, Wang TY, Lu CC, Huang CJ, Lee TY. The safety and efficacy of alfentanil-based induction in bronchoscopy sedation: a randomized, double-blind, controlled trial. Medicine (Baltimore). 2016;95:e5101. Ahonen J, Olkkola KT, Hynynen M, Seppala T, Ikonen S, Jantti V, Remmerie B, Eye J, Kallio A. Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery. Br J Anaesth. 2000;85:533–540. Cuiabano IS, Naves RP, Diehl RBA. Comparison of the recovery profile of sufentanil and remifentanil in total intravenous anesthesia: a systematic review and meta-analysis of randomized controlled trials. Braz J Anesthesiol. 2025;75(1):844558. doi:10.1016/j.bjane.2024.844558. Shafer SL, Varvel JR. Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology. 1991;74(1):53–63. doi:10.1097/00000542-199101000-00010. Sridharan K, Sivaramakrishnan G. Comparison of fentanyl, remifentanil, sufentanil and alfentanil in combination with propofol for general anesthesia: a systematic review and meta-analysis of randomized controlled trials. Curr Clin Pharmacol. 2019;14(2):116–124. doi:10.2174/1567201816666190313160438. Kateliya R, Madhukant, Dubey M, Chandra S, Sahay N. Comparison of recovery profiles in target-controlled infusions (TCI) versus manually controlled infusions for total intravenous anesthesia (TIVA) in laparoscopic surgeries: a randomized controlled trial. J Anaesthesiol Clin Pharmacol. 2023;39(2):258–263. doi:10.4103/joacp.joacp_396_21. Bidkar PU, Dey A, Chatterjee P, Ramadurai R, Joy JJ. Target-controlled infusion: past, present, and future. J Anaesthesiol Clin Pharmacol. 2024;40(3):371–380. doi:10.4103/joacp.joacp_64_23. Rong LQ, Kamel MK, Rahouma M, Naik A, Anousheh R, Loarte PS, Pryor KO, Gaudino M, Girardi LN. High-dose versus low-dose opioid anesthesia in adult cardiac surgery: a meta-analysis. J Clin Anesth. 2019;57:57–62. May AM, Kazakov J, Strohl KP. Predictors of intraprocedural respiratory bronchoscopy complications. J Bronchology Interv Pulmonol. 2020;27(2):135–141. doi:10.1097/LBR.0000000000000619. Sigmond N, Baechtold M, Schumacher PM, Hartwich V, Schnider TW, Luginbühl M. Pharmacokinetic parameter sets of alfentanil revisited: optimal parameters for use in target controlled infusion and anaesthesia display systems. Br J Anaesth. 2013;111(2):197–208. doi:10.1093/bja/aet049. Potdar MP, Kamat LL, Save MP. Cost efficiency of target-controlled inhalational anesthesia. J Anaesthesiol Clin Pharmacol. 2014;30(2):222–227. doi:10.4103/0970-9185.130026. Colt HG, Morris JF. Fiberoptic bronchoscopy without premedication: a retrospective study. Chest. 1990;98(6):1327–1330. Dershwitz M, Rosow CE, DiBiase PM, Zaslavsky A. Comparison of the sedative effects of butorphanol and midazolam. Anesthesiology. 1991;74(4):717–724. Hughes MA, Glass PS, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 1992;76(3):334–341. Additional Declarations No competing interests reported. Supplementary Files Supplementarytable1.csv CONSORT2025checklistDH.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 11 Nov, 2025 Reviewers agreed at journal 10 Nov, 2025 Reviewers invited by journal 10 Nov, 2025 Editor assigned by journal 04 Nov, 2025 Editor invited by journal 16 Oct, 2025 Submission checks completed at journal 15 Oct, 2025 First submitted to journal 15 Oct, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7843053","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":547135162,"identity":"cba076e9-195b-436a-bb78-95f1c7306f1e","order_by":0,"name":"Jiayuan Niu","email":"","orcid":"","institution":"Dalian Medical University","correspondingAuthor":false,"prefix":"","firstName":"Jiayuan","middleName":"","lastName":"Niu","suffix":""},{"id":547135163,"identity":"38dd2fb1-3376-4777-8889-5962d8a35a7f","order_by":1,"name":"Dan Xu","email":"","orcid":"","institution":"Dalian Medical 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10:08:22","extension":"html","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":125809,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7843053/v1/fb4ae617d113eeed89f1d547.html"},{"id":96285498,"identity":"7db5de65-b10b-46aa-81ea-58fd948b0bec","added_by":"auto","created_at":"2025-11-19 11:57:50","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":69533,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eStudy flow chart. \u003c/strong\u003eA total of 98 patients were screened for eligibility between April 2023 and September 2023. Of these, 5 patients declined to sign informed consent, 2 had intraoperative bleeding requiring surgery termination, and 1 was converted to specialized treatment; all were excluded. The remaining 90 patients were randomized into three groups: Group A (Alfentanil TCI, n=30), Group S (Sufentanil TCI, n=30), and Group M (Alfentanil Bolus, n=30). All randomized patients completed follow-up and were included in the final analysis.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7843053/v1/9b2ef3b78b2440b6daa94ccc.png"},{"id":96364423,"identity":"18d0facb-fc9f-4854-92ed-48d8fac1cf8b","added_by":"auto","created_at":"2025-11-20 10:09:18","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":238651,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHemodynamic measurements during flexible bronchoscopy. \u003c/strong\u003ePanel A shows heart rate, Panel B shows systolic (solid lines, circles) and diastolic (dashed lines, squares) blood pressure, Panel C displays mean arterial pressure, and Panel D presents oxygen saturation across five timepoints: T0 (baseline), Ta (pre-procedure), T1 (post-lidocaine), T2 (scope through glottis), T3 (scope at carina). Data are presented as mean ± standard error for Group A (Alfentanil TCI, n=30), Group S (Sufentanil TCI, n=30), and Group M (Alfentanil Bolus, n=30).\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7843053/v1/cf745a6ee3789f47cf1a6550.png"},{"id":96602826,"identity":"d7d7ad3a-5f4e-4ee5-8835-456f18fa2d95","added_by":"auto","created_at":"2025-11-24 09:02:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1774898,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7843053/v1/f947483a-552f-4834-8a39-505de78a6171.pdf"},{"id":96285496,"identity":"d83acee5-4561-473f-b099-567800dc0192","added_by":"auto","created_at":"2025-11-19 11:57:50","extension":"csv","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":14209,"visible":true,"origin":"","legend":"","description":"","filename":"Supplementarytable1.csv","url":"https://assets-eu.researchsquare.com/files/rs-7843053/v1/4f9d8ce4a55d0df653ca659f.csv"},{"id":96285502,"identity":"038bfc37-b7c2-4fd9-b9cd-6c2daf44f052","added_by":"auto","created_at":"2025-11-19 11:57:50","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":14572,"visible":true,"origin":"","legend":"","description":"","filename":"CONSORT2025checklistDH.docx","url":"https://assets-eu.researchsquare.com/files/rs-7843053/v1/b994a3ae99c0233b79e41b11.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Safety and Efficacy of Alfentanil Compared to Sufentanil in Target- Controlled Infusion During Flexible Bronchoscopy: A Randomized Controlled Trial","fulltext":[{"header":"Background","content":"\u003cp\u003eFlexible bronchoscopy (FB) represents one of the most essential diagnostic and therapeutic modalities in contemporary pulmonary medicine, enabling direct visualization and sampling of the tracheobronchial tree with relatively low morbidity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. However, the procedure involves significant patient discomfort due to laryngeal stimulation, cough reflex activation, and psychological distress, necessitating optimal anesthetic management to ensure patient tolerance while maintaining safety [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe evolution of procedural sedation for bronchoscopy has progressed from simple topical anesthesia to multimodal approaches incorporating systemic sedatives and analgesics [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Current guidelines recommend combination protocols utilizing benzodiazepines, propofol, and opioid analgesics to achieve adequate sedation depth while preserving respiratory drive and hemodynamic stability [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Among opioid options, alfentanil and sufentanil have emerged as preferred agents due to their favorable pharmacokinetic profiles, though comparative efficacy data remain limited.\u003c/p\u003e\u003cp\u003eAlfentanil, a rapid-onset, short-duration synthetic fentanyl analog, exhibits pharmacological advantages including faster equilibration between plasma and effect-site concentrations, predictable dose-response relationships, and minimal accumulation with repeated dosing [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. These properties make alfentanil particularly suitable for procedures requiring precise titration and rapid recovery. Conversely, sufentanil offers superior potency [approximately 5\u0026ndash;10 fold greater than alfentanil] and potentially enhanced analgesic efficacy, though with correspondingly longer context-sensitive half-life [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eTarget-controlled infusion (TCI) technology represents a significant advancement in anesthetic drug delivery, utilizing pharmacokinetic modeling to achieve and maintain predetermined plasma or effect-site concentrations [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. TCI systems offer theoretical advantages over traditional bolus dosing, including reduced inter-patient variability, improved titration precision, and enhanced recovery predictability [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, the optimal opioid selection and delivery method for bronchoscopic procedures remains undefined.\u003c/p\u003e\u003cp\u003ePrevious investigations comparing opioid agents during bronchoscopy have yielded inconsistent results, often limited by small sample sizes, heterogeneous protocols, and the lack of standardized outcome measures [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Furthermore, direct comparisons between TCI and conventional bolus dosing regimens are scarce, limiting evidence-based decision-making in clinical practice.\u003c/p\u003e\u003cp\u003eTherefore, this prospective, randomized, controlled study was designed to comprehensively compare the safety and efficacy of alfentanil versus sufentanil target-controlled infusion and conventional alfentanil bolus administration during flexible bronchoscopy, with particular attention to procedural comfort, hemodynamic stability, and recovery characteristics.\u003c/p\u003e"},{"header":"Methods","content":"\u003ch3\u003e\u003cstrong\u003eStudy Design and Ethics\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThis prospective, randomized, double-blind, controlled clinical trial was conducted from February 2022 to March 2023 at the Second Affiliated Hospital of Dalian Medical University, following approval by the institutional review board ([Ethics Review No. 135 of 2023]) and registration with the Chinese Clinical Trial Registry ([ChiCTR2400089901]). The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from all participants prior to enrollment.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eParticipants\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eAdult patients (aged 18-75 years) scheduled for elective diagnostic or therapeutic flexible bronchoscopy were eligible for inclusion. Inclusion criteria comprised: American Society of Anesthesiologists (ASA) physical status I-III, body mass index (BMI) \u0026lt; 28 kg/m\u0026sup2;, and ability to provide informed consent. Exclusion criteria included: known hypersensitivity to study medications, severe cardiovascular disease (ejection fraction \u0026lt; 40%, unstable angina, recent myocardial infarction), significant respiratory compromise (baseline SpO₂ \u0026lt; 90% on room air), hepatic or renal impairment, pregnancy or lactation, psychiatric disorders precluding cooperation, and emergency procedures.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eRandomization and Blinding\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eEligible patients were randomly allocated using computer-generated randomization sequences in sealed opaque envelopes to one of three treatment groups: Group A (alfentanil TCI, target concentration 35 ng/mL), Group S (sufentanil TCI, target concentration 0.2 ng/mL), or Group M (alfentanil intravenous bolus, 5 \u0026mu;g/kg). Randomization was stratified by ASA status and procedure type (diagnostic versus therapeutic). Study medications were prepared by an independent pharmacist not involved in patient care or data collection. Patients remained blinded (single-blinded) to treatment allocation throughout the study period.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eAnesthetic Protocol\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eAll patients underwent standardized preoperative assessment, including medical history, physical examination, and laboratory investigations as clinically indicated. Baseline vital signs were recorded, and intravenous access was established using an 18-gauge peripheral cannula. Continuous monitoring included electrocardiography, non-invasive blood pressure, pulse oximetry, and capnography when clinically appropriate.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePre-medication\u003c/strong\u003e: All patients received midazolam 0.02 mg/kg intravenously 10 minutes prior to procedure initiation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInduction\u003c/strong\u003e: Standardized co-induction was performed using remazolam 0.1 mg/kg intravenously across all groups, followed by study drug administration according to randomization: - Group A: Alfentanil TCI initiated at target plasma concentration 35 ng/mL - Group S: Sufentanil TCI initiated at target plasma concentration 0.2 ng/mL\u003cbr\u003e\u0026nbsp;- Group M: Alfentanil bolus 5 \u0026mu;g/kg administered over 2 minutes\u003c/p\u003e\n\u003cp\u003eTCI systems utilized validated pharmacokinetic models (Maitre model for alfentanil, Gepts model for sufentanil) with plasma targeting mode.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaintenance\u003c/strong\u003e: Propofol boluses (0.5 mg/kg) were administered as needed to maintain adequate sedation depth, defined by Modified Observer\u0026rsquo;s Assessment of Alertness/Sedation (MOAA/S) score 2-3. Target-controlled infusions were maintained throughout the procedure without adjustment unless clinically contraindicated.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTopical Anesthesia\u003c/strong\u003e: Standardized topical lidocaine (1%, maximum 7 mg/kg) was applied to the nasal passages, oropharynx, and vocal cords as per institutional protocol.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eOutcome Measures\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003e\u003cstrong\u003ePrimary Outcomes\u003c/strong\u003e: 1. Hemodynamic stability assessed by heart rate, blood pressure, mean arterial pressure (MAP), and oxygen saturation (SpO₂) measured at predefined timepoints: T0 (baseline), Ta (pre-procedure), T1 (post-lidocaine application), T2 (bronchoscope passage through glottis), T3 (bronchoscope at carina) 2. Cough frequency during procedure (assessed by independent observer using standardized scale)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSecondary Outcomes\u003c/strong\u003e: 1. Timing parameters: induction time (drug administration to adequate sedation), procedure duration, awakening time (procedure end to spontaneous eye opening), and total sedation time. 2. Respiratory complications: incidence of respiratory depression, requirement for manual ventilation or airway intervention, and chokes requiring intervention. 3. Additional medication requirements: number and dose of propofol. 4. Procedural quality: bronchoscopist satisfaction score. 5. Recovery characteristics: post-procedure adverse events.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eStatistical Analysis\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe sample size calculation was based on previous studies suggesting a 30% reduction in cough incidence as clinically significant [15]. Assuming \u0026alpha; = 0.05, \u0026beta; = 0.20, and a 15% dropout rate, 30 patients per group were required to detect this difference with adequate power.\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using SPSS version 25.0 (IBM Corp., Armonk, NY, USA). Normality of continuous variables was assessed using Shapiro-Wilk tests. Normally distributed data are presented as mean \u0026plusmn; standard deviation and compared using one-way ANOVA with post-hoc Tukey tests. Non-normally distributed data are presented as median (interquartile range) and analyzed using Kruskal-Wallis tests with pairwise Mann-Whitney U comparisons. Categorical variables are expressed as frequencies and percentages, compared using \u0026chi;\u0026sup2; or Fisher\u0026rsquo;s exact tests as appropriate.\u003c/p\u003e\n\u003cp\u003eMultiple comparisons were adjusted using Bonferroni correction where applicable. Statistical significance was defined as P \u0026lt; 0.05 (two-tailed). All analyses were performed on an intention-to-treat basis with sensitivity analyses on per-protocol populations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCONSORT Statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study adheres to the CONSORT guidelines for reporting randomized controlled trials. A completed CONSORT 2025 checklist is provided as an additional file to facilitate full evaluation and utilization of our methodology.\u0026nbsp;\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eParticipant Flow and Baseline Characteristics\u003c/h2\u003e\u003cp\u003eFrom April to September 2023, 98 patients were initially screened for eligibility. Five individuals declined to provide informed consent and were excluded, while two procedures were terminated due to intraoperative bleeding, and one case required conversion to a specialized treatment, leading to exclusion. Consequently, 90 patients were successfully enrolled and randomized into three groups of 30 each. All randomized patients completed the study without loss to follow-up or significant protocol deviations (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eBaseline demographic and clinical characteristics were well-balanced across treatment groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Mean age was 62.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.7, 62.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5, and 63.3\u0026thinsp;\u0026plusmn;\u0026thinsp;9.1 years for Groups A, S, and M, respectively (P\u0026thinsp;=\u0026thinsp;0.959). Sex distribution, BMI, ASA classification, and Modified Mallampati scores showed no significant inter-group differences (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05), confirming successful randomization.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eDemographic and baseline characteristics by treatment group. Data are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation or n (%). P-values represent comparisons across all three groups.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup A\u003c/p\u003e\u003cp\u003eAlfentanil TCI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGroup S\u003c/p\u003e\u003cp\u003eSufentanil TCI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGroup M\u003c/p\u003e\u003cp\u003eAlfentanil Bolus\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge (years), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e62.93\u0026thinsp;\u0026plusmn;\u0026thinsp;7.67\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e62.70\u0026thinsp;\u0026plusmn;\u0026thinsp;7.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e63.30\u0026thinsp;\u0026plusmn;\u0026thinsp;9.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.959\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex, n (%)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eMale\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19 (63.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (76.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e20 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.510\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eFemale\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (36.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (23.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.510\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBMI (kg/m\u0026sup2;), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22.68\u0026thinsp;\u0026plusmn;\u0026thinsp;2.49\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.69\u0026thinsp;\u0026plusmn;\u0026thinsp;2.57\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22.62\u0026thinsp;\u0026plusmn;\u0026thinsp;2.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.993\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eASA classification, n (%)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eClass II\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24 (80.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23 (76.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e19 (63.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.148\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eClass III\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (20.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7 (23.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11 (36.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.148\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eModified Mallampati Score, n (%)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eGrade I\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (60.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.437\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGrade II\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (33.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e15 (50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.437\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003ePrimary Outcomes\u003c/h2\u003e\u003cp\u003e\u003cstrong\u003eHemodynamic Stability\u003c/strong\u003e\u003cp\u003eAll three anesthetic regimens maintained acceptable hemodynamic stability throughout the procedure (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e; Supplementary Table\u0026nbsp;1). While heart rate, blood pressure, mean arterial pressure, and oxygen saturation showed generally similar patterns across groups with expected responses to procedural stimulation, some time-dependent differences were observed. Heart rate showed significant variations between groups at post-induction and later time points, and diastolic blood pressure demonstrated differences during the procedural period. However, all hemodynamic parameters remained within clinically acceptable ranges throughout the study period. All patients maintained SpO₂ levels above 86% without requiring supplemental oxygen beyond standard care.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eCough Incidence\u003c/b\u003e: Significant differences were observed in procedural cough frequency (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Both alfentanil groups demonstrated superior cough suppression compared to sufentanil TCI (Group A: 1 [1-1.25] episodes; Group M: 1 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] episodes versus Group S: 2 [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] episodes; P\u0026thinsp;=\u0026thinsp;0.006). Post-hoc analysis revealed statistically significant differences between Group S and both alfentanil groups (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), while Groups A and M showed comparable cough control (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePrimary outcome measures by treatment group. Data are presented as median (interquartile range) or n (%). Asterisk (*) indicates statistical significance (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). T0 (baseline), Ta (pre-procedure), T1 (post-lidocaine), T2 (scope through glottis), T3 (scope at carina).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePrimary Outcome Measure\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup A\u003c/p\u003e\u003cp\u003eAlfentanil TCI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGroup S\u003c/p\u003e\u003cp\u003eSufentanil TCI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGroup M\u003c/p\u003e\u003cp\u003eAlfentanil Bolus\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eIncidence of cough\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(1, 1.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e(1, 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(1, 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.006*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHeart rate\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eT0 - Ta - T1 - T2 - T3\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e83 (78, 93)\u003c/p\u003e\u003cp\u003e90 (85, 97)\u003c/p\u003e\u003cp\u003e96 (89, 105)\u003c/p\u003e\u003cp\u003e102 (88, 108)\u003c/p\u003e\u003cp\u003e98 (87, 102)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e83 (74, 95)\u003c/p\u003e\u003cp\u003e92 (84, 99)\u003c/p\u003e\u003cp\u003e96 (80, 104)\u003c/p\u003e\u003cp\u003e93 (83, 103)\u003c/p\u003e\u003cp\u003e88 (82, 98)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e80 (75, 88)\u003c/p\u003e\u003cp\u003e84 (74, 89)\u003c/p\u003e\u003cp\u003e86 (76, 93)\u003c/p\u003e\u003cp\u003e88 (79, 96)\u003c/p\u003e\u003cp\u003e92 (80, 97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.588\u003c/p\u003e\u003cp\u003e0.010*\u003c/p\u003e\u003cp\u003e0.194\u003c/p\u003e\u003cp\u003e0.032*\u003c/p\u003e\u003cp\u003e0.027*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSystolic blood pressure\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eT0 - Ta - T1 - T2 - T3\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e134 (122, 146)\u003c/p\u003e\u003cp\u003e118 (107, 127)\u003c/p\u003e\u003cp\u003e122 (107, 142)\u003c/p\u003e\u003cp\u003e126 (103, 139)\u003c/p\u003e\u003cp\u003e123 (104, 139)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e131 (122, 138)\u003c/p\u003e\u003cp\u003e116 (105, 124)\u003c/p\u003e\u003cp\u003e123 (100, 139)\u003c/p\u003e\u003cp\u003e115 (103, 136)\u003c/p\u003e\u003cp\u003e114 (105, 138)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e136 (122, 150)\u003c/p\u003e\u003cp\u003e118 (105, 128)\u003c/p\u003e\u003cp\u003e110 (99, 126)\u003c/p\u003e\u003cp\u003e121 (108, 134)\u003c/p\u003e\u003cp\u003e115 (105, 135)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.474\u003c/p\u003e\u003cp\u003e0.551\u003c/p\u003e\u003cp\u003e0.057\u003c/p\u003e\u003cp\u003e0.530\u003c/p\u003e\u003cp\u003e0.176\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDiastolic blood pressure\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eT0 - Ta - T1 - T2 - T3\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e82 (72, 86)\u003c/p\u003e\u003cp\u003e74 (65, 85)\u003c/p\u003e\u003cp\u003e83 (68, 94)\u003c/p\u003e\u003cp\u003e76 (69, 92)\u003c/p\u003e\u003cp\u003e75 (69, 89)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e80 (72, 86)\u003c/p\u003e\u003cp\u003e70 (59, 76)\u003c/p\u003e\u003cp\u003e72 (64, 83)\u003c/p\u003e\u003cp\u003e74 (66, 81)\u003c/p\u003e\u003cp\u003e72 (65, 81)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e82 (73, 89)\u003c/p\u003e\u003cp\u003e71 (64, 75)\u003c/p\u003e\u003cp\u003e67 (63, 78)\u003c/p\u003e\u003cp\u003e72 (66, 77)\u003c/p\u003e\u003cp\u003e70 (64, 76)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.437\u003c/p\u003e\u003cp\u003e0.245\u003c/p\u003e\u003cp\u003e0.002*\u003c/p\u003e\u003cp\u003e0.085\u003c/p\u003e\u003cp\u003e0.018*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMean arterial pressure\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eT0 - Ta - T1 - T2 - T3\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e99 (89, 110)\u003c/p\u003e\u003cp\u003e87 (79, 104)\u003c/p\u003e\u003cp\u003e94 (83, 110)\u003c/p\u003e\u003cp\u003e90 (81, 111)\u003c/p\u003e\u003cp\u003e90 (82, 105)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e95 (90, 103)\u003c/p\u003e\u003cp\u003e86 (76, 91)\u003c/p\u003e\u003cp\u003e86 (78, 101)\u003c/p\u003e\u003cp\u003e88 (77, 96)\u003c/p\u003e\u003cp\u003e87 (77, 96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e100 (92, 109)\u003c/p\u003e\u003cp\u003e87 (79, 93)\u003c/p\u003e\u003cp\u003e81 (72, 96)\u003c/p\u003e\u003cp\u003e90 (83, 97)\u003c/p\u003e\u003cp\u003e90 (77, 94)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.615\u003c/p\u003e\u003cp\u003e0.889\u003c/p\u003e\u003cp\u003e0.001*\u003c/p\u003e\u003cp\u003e0.629\u003c/p\u003e\u003cp\u003e0.283\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePeripheral oxygen saturation\u003c/b\u003e:\u003c/p\u003e\u003cp\u003e\u003cb\u003eT0 - Ta - T1 - T2 - T3\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e98 (98, 99)\u003c/p\u003e\u003cp\u003e98 (96, 99)\u003c/p\u003e\u003cp\u003e95 (90, 97)\u003c/p\u003e\u003cp\u003e94 (91, 97)\u003c/p\u003e\u003cp\u003e94 (91, 96)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e98 (97, 99)\u003c/p\u003e\u003cp\u003e98 (95, 99)\u003c/p\u003e\u003cp\u003e96 (93, 99)\u003c/p\u003e\u003cp\u003e94 (90, 96)\u003c/p\u003e\u003cp\u003e94 (90, 97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e98 (96, 100)\u003c/p\u003e\u003cp\u003e99 (98, 100)\u003c/p\u003e\u003cp\u003e97 (91, 98)\u003c/p\u003e\u003cp\u003e94 (89, 98)\u003c/p\u003e\u003cp\u003e93 (89, 97)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.707\u003c/p\u003e\u003cp\u003e0.064\u003c/p\u003e\u003cp\u003e0.038*\u003c/p\u003e\u003cp\u003e0.787\u003c/p\u003e\u003cp\u003e0.847\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eSecondary Outcomes\u003c/h2\u003e\u003cp\u003e\u003cb\u003eTiming Parameters\u003c/b\u003e: Marked differences were observed in procedural timing (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e; Supplementary Table\u0026nbsp;1). Induction time was significantly shorter with alfentanil TCI compared to other groups (Group A: 2 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] minutes versus Group S: 3 [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] minutes and Group M: 3 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] minutes; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Most notably, awakening time demonstrated substantial variation, with alfentanil bolus providing the fastest recovery (Group M: 7.5 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] minutes versus Group A: 10 [8.75-12] minutes versus Group S: 19 [14.25-22] minutes; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), representing a 2.5-fold difference between fastest and slowest recovery regimens.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eSecondary outcome measures by treatment group. Data are presented as median (interquartile range). Asterisk (*) indicates statistical significance (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSecondary Outcome Measure\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eGroup A\u003c/p\u003e\u003cp\u003eAlfentanil TCI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eGroup S\u003c/p\u003e\u003cp\u003eSufentanil TCI\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eGroup M\u003c/p\u003e\u003cp\u003eAlfentanil Bolus\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003eTiming parameters\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInduction time (min)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e(2, 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e(3, 4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e(2, 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eProcedure duration (min)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11\u003c/p\u003e\u003cp\u003e(9, 14.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11.5\u003c/p\u003e\u003cp\u003e(9.75, 14)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e10.5\u003c/p\u003e\u003cp\u003e(8.75, 15)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.816\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAwakening time (min)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003cp\u003e(8.75, 12)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19\u003c/p\u003e\u003cp\u003e(14.25, 22)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e7.5\u003c/p\u003e\u003cp\u003e(5, 10)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal sedation time (min)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e14\u003c/p\u003e\u003cp\u003e(11.75, 17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15\u003c/p\u003e\u003cp\u003e(12.75, 17)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e14.5\u003c/p\u003e\u003cp\u003e(11.7, 17.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.401\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRespiratory complications\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRespiratory depression incidence\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19\u003c/p\u003e\u003cp\u003e(63.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23\u003c/p\u003e\u003cp\u003e(76.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e22\u003c/p\u003e\u003cp\u003e(73.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.621\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eManual adjustment for respiratory depression\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(0, 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(0, 2.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(0, 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.539\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eChokes requiring intervention\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(0, 1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(1, 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(0, 1.25)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.056\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAdditional medication requirements\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eNumber of additional propofol\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.5\u003c/p\u003e\u003cp\u003e(1, 2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003cp\u003e(1, 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1\u003c/p\u003e\u003cp\u003e(1, 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.642\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal additional propofol dose (mg)\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e55\u003c/p\u003e\u003cp\u003e(30, 82.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e60\u003c/p\u003e\u003cp\u003e(40, 110)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e40\u003c/p\u003e\u003cp\u003e(30, 92.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.533\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eProcedural quality\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBronchoscopist satisfaction score\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003emedian (IQR)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003cp\u003e(3, 5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e(2, 4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e3\u003c/p\u003e\u003cp\u003e(3, 3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.060\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eRespiratory Safety\u003c/b\u003e: Respiratory depression rates were comparable across groups (Group A: 63.3%, Group S: 76.7%, Group M: 73.3%; P\u0026thinsp;=\u0026thinsp;0.621). Importantly, all episodes were mild and responded to simple interventions (tactile stimulation, jaw thrust) without requiring positive pressure ventilation or reversal agents. No significant differences were observed in manual airway intervention requirements or supplemental oxygen needs.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMedication Requirements\u003c/strong\u003e\u003cp\u003eTotal propofol consumption and rescue medication needs showed no significant inter-group differences (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Additional propofol doses were required 1.5 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], 2 [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and 1 [\u003cspan additionalcitationids=\"CR2\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] times, and the total doses administered were 55 [30\u0026ndash;82.5] mg, 60 [40\u0026ndash;110] mg, and 40 [30\u0026ndash;92.5] mg for Groups A, S, and M, respectively (P\u0026thinsp;=\u0026thinsp;0.642 and P\u0026thinsp;=\u0026thinsp;0.533).\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eProcedural Quality\u003c/strong\u003e\u003cp\u003eBronchoscopist satisfaction scores were consistently high across all groups without significant differences.\u003c/p\u003e\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eAdverse Events\u003c/h2\u003e\u003cp\u003eNo serious adverse events related to study interventions were observed. Minor adverse events included transient hypotension (n\u0026thinsp;=\u0026thinsp;3), brief oxygen desaturation (n\u0026thinsp;=\u0026thinsp;5), and post-procedure nausea (n\u0026thinsp;=\u0026thinsp;2), distributed evenly across groups. No emergency interventions, procedure terminations, or prolonged recovery complications occurred.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis randomized controlled trial provides comprehensive comparative evidence regarding opioid selection and delivery methods for flexible bronchoscopy sedation. The principal findings demonstrate that alfentanil-based regimens, regardless of delivery method, offer superior cough suppression compared to sufentanil TCI while maintaining equivalent safety profiles. Additionally, significant differences in procedural timing favor alfentanil TCI for rapid induction and alfentanil bolus for expedited recovery.\u003c/p\u003e\u003cdiv id=\"Sec16\" class=\"Section2\"\u003e\u003ch2\u003eClinical Implications of Cough Control\u003c/h2\u003e\u003cp\u003eThe observed superior antitussive effect of alfentanil represents a clinically meaningful finding with direct procedural implications. Cough suppression during bronchoscopy is essential for optimal visualization, adequate sampling, and procedural safety [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Excessive coughing can compromise diagnostic yield, increase procedural duration, elevate aspiration risk, and contribute to patient discomfort and procedure-related anxiety [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The statistically significant reduction in cough episodes with alfentanil (effect size Cohen\u0026rsquo;s d = -0.95, representing moderate-to-large clinical effect) suggests meaningful improvement in procedural conditions.\u003c/p\u003e\u003cp\u003eThe mechanism underlying differential antitussive efficacy likely relates to pharmacokinetic and receptor binding characteristics. Alfentanil\u0026rsquo;s rapid onset and high \u0026micro;-opioid receptor selectivity may provide more effective cough reflex suppression at the medullary level compared to sufentanil\u0026rsquo;s more gradual onset profile, despite the latter\u0026rsquo;s higher potency [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These findings align with previous investigations suggesting alfentanil\u0026rsquo;s superior antitussive properties in bronchoscopic applications [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003eTiming Considerations and Clinical Workflow\u003c/h2\u003e\u003cp\u003eThe dramatic differences observed in induction and recovery times carry substantial implications for clinical workflow and resource utilization. Alfentanil TCI\u0026rsquo;s faster induction (33% time reduction) facilitates procedure scheduling efficiency [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] and reduces patient anxiety [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] associated with prolonged onset periods. More importantly, the 2.5-fold difference in awakening times between regimens directly impacts recovery bay utilization [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], nursing requirements [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], and overall procedural throughput [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe prolonged recovery associated with sufentanil TCI (median 19 vs 7.5 minutes for alfentanil bolus) likely reflects the drug\u0026rsquo;s longer context-sensitive half-life and higher lipophilicity, resulting in tissue redistribution and accumulation [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. This finding challenges the common assumption that TCI systems uniformly provide predictable recovery profiles [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e], emphasizing the continued importance of drug selection over delivery method sophistication.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eSafety Profile and Hemodynamic Stability\u003c/h2\u003e\u003cp\u003eThe absence of significant hemodynamic differences across all regimens provides reassuring evidence regarding cardiovascular safety [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. All three approaches demonstrated expected physiological responses to bronchoscopic stimulation without clinically significant blood pressure fluctuations, arrhythmias, or desaturation events. The comparable respiratory depression rates, while numerically high, reflect the sensitive definition employed (any decrease in respiratory rate or oxygen saturation) rather than clinically concerning events, as evidenced by the lack of intervention requirements [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThese safety findings support the clinical viability of all three regimens for routine bronchoscopic procedures, with selection primarily driven by procedural priorities rather than safety concerns. The maintained SpO₂ levels above 86% across all groups exceed accepted thresholds for procedural sedation, while the absence of serious adverse events reinforces the appropriateness of current dosing protocols.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eTarget-Controlled Infusion Considerations\u003c/h2\u003e\u003cp\u003eThe mixed results regarding TCI advantages warrant careful interpretation. While alfentanil TCI provided fastest induction [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e], it did not demonstrate superiority in recovery parameters compared to conventional bolus dosing. This finding suggests that TCI benefits may be drug-specific rather than universally applicable across all opioid agents [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The precise concentration control offered by TCI systems may be most advantageous for drugs with narrow therapeutic windows or unpredictable pharmacokinetic profiles, which may not apply to alfentanil given its favorable characteristics.\u003c/p\u003e\u003cp\u003eFurthermore, the economic implications of TCI systems, including equipment costs, training requirements, and technical complexity, must be balanced against demonstrated clinical benefits [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The current results suggest that conventional bolus dosing may remain appropriate for many bronchoscopic applications, particularly when rapid recovery is prioritized.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eStudy Limitations\u003c/h2\u003e\u003cp\u003eFirst, the single-center design may limit generalizability to different patient populations or practice environments. Second, the relatively small sample size, while adequately powered for primary endpoints, may have limited ability to detect rare adverse events or subtle differences in secondary outcomes. Third, the study population excluded high-risk patients, and results may not apply to critically ill or severely compromised individuals.\u003c/p\u003e\u003cp\u003eThe use of estimated rather than measured drug concentrations in plasma represents another limitation, though this reflects standard clinical practice where TCI systems rely on pharmacokinetic modeling rather than real-time drug level monitoring. Finally, the absence of long-term follow-up prevents assessment of delayed complications or patient satisfaction beyond the immediate recovery period.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003eClinical Recommendations\u003c/h2\u003e\u003cp\u003eBased on these findings, we recommend alfentanil over sufentanil for flexible bronchoscopy sedation due to superior cough control and more favorable timing profiles. The choice between TCI and bolus delivery should be guided by specific procedural priorities: TCI for situations requiring rapid onset (urgent procedures, anxious patients), and bolus dosing when expedited recovery is paramount (outpatient settings, high-volume practices, limited recovery resources).\u003c/p\u003e\u003cp\u003eThese recommendations align with contemporary trends toward personalized perioperative care, where anesthetic selection is tailored to individual patient characteristics and procedural requirements rather than utilizing universal protocols [\u003cspan additionalcitationids=\"CR32\" citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Future investigations should explore patient-specific factors that might predict optimal anesthetic selection and evaluate the cost-effectiveness of different regimens across diverse healthcare settings.\u003c/p\u003e\u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThis randomized controlled trial demonstrates that alfentanil-based sedation regimens provide superior cough control compared to sufentanil TCI during flexible bronchoscopy while maintaining equivalent safety profiles. Alfentanil TCI offers fastest induction, while conventional alfentanil bolus dosing enables most rapid recovery. The choice between alfentanil delivery methods should be individualized based on specific clinical priorities and procedural requirements.\u003c/p\u003e\u003cp\u003eThese findings provide evidence-based guidance for anesthetic selection in bronchoscopic procedures and support alfentanil as the preferred opioid agent for this indication. The substantial differences in recovery times highlight the continued importance of drug selection over delivery method sophistication in achieving optimal procedural outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"455\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eTCI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eTarget-Controlled Infusion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eFB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eFlexible Bronchoscopy\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eASA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eAmerican Society of Anesthesiologists\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eBMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eBody Mass Index\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMAP\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMean Arterial Pressure\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSpO₂\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eOxygen Saturation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eMOAA/S\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eModified Observer’s Assessment of Alertness/Sedation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eIRB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eInstitutional Review Board\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eIQR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eInterquartile Range\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eSD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"bottom\"\u003e\n \u003cp\u003eStandard Deviation\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis prospective, randomized, double-blind, controlled clinical trial was conducted with the approval of the institutional review board ([Ethics Review No. 135 of 2023]) by Second Affiliated Hospital, Dalian Medical University, and registration with the Chinese Clinical Trial Registry ([ChiCTR2400089901]). The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. Written informed consent was obtained from all participants prior to enrollment, ensuring voluntary participation and the protection of patient rights throughout the study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll participants provided written informed consent for the publication of this study\u0026rsquo;s data, analyses, and findings. The consent included permission to publish anonymized data in scientific journals and conference presentations, ensuring individuals cannot be identified from any published material. This consent was obtained prior to participation and was documented systematically in accordance with institutional and ethical standards.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data supporting the findings of this study are available in Supplementary Table 1, which is provided with this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNone.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e[DH, JN, DX]: Conceptualization, methodology, investigation, writing\u0026mdash;original draft preparation. [JN, DX, SL, DH]: Data curation, formal analysis, writing\u0026mdash;review and editing. All authors approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank the bronchoscopy suite nursing staff for their dedicated support during data collection and the patients who participated in this study. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMondoni M, Rinaldo RF, Carlucci P, Terraneo S, Saderi L, Centanni S, Sotgiu G. Bronchoscopic sampling techniques in the era of technological bronchoscopy. Pulmonology. 2022;28:461\u0026ndash;471.\u003c/li\u003e\n\u003cli\u003eAfriyie-Mensah JS, Kwarteng E, Tetteh J, Sereboe L, Forson A. Flexible bronchoscopy in a tertiary healthcare facility: a review of indications and outcomes. Ghana Med J. 2021;55(1):18\u0026ndash;25. doi:10.4314/gmj.v55i1.4.\u003c/li\u003e\n\u003cli\u003eMagazine R, Bhatnagar V, Guha K, Ghosh S, Ninan J, Dutta A. Effect of bronchoscopist-directed sedation and other factors on patient comfort during diagnostic flexible bronchoscopy. Indian J Chest Dis Allied Sci. 2022;64(4):259\u0026ndash;265.\u003c/li\u003e\n\u003cli\u003ePoi PJ, Chuah SY, Srinivas P, Liam CK. Common fears of patients undergoing bronchoscopy. Eur Respir J. 1998;11(5):1147\u0026ndash;1149. doi:10.1183/09031936.98.11051147.\u003c/li\u003e\n\u003cli\u003eJos\u0026eacute; RJ, Shaefi S, Navani N. Sedation for flexible bronchoscopy: current and emerging evidence. Eur Respir Rev. 2013;22:106.\u003c/li\u003e\n\u003cli\u003eWahidi MM, Jain P, Jantz M, Lee P, Mackensen GB, Barbour SY, Lamb C, Silvestri GA. American College of Chest Physicians consensus statement on the use of topical anesthesia, analgesia, and sedation during flexible bronchoscopy in adult patients. Chest. 2011;140:1342\u0026ndash;1350.\u003c/li\u003e\n\u003cli\u003eWang L, Wang M, Xu R, Li J, Cao Y, Ji F. Comparative analysis of guidelines and recommendations for sedation during flexible bronchoscopy: a narrative review. Eur Respir Rev. 2025;34(177):250045. doi:10.1183/16000617.0045-2025.\u003c/li\u003e\n\u003cli\u003eBovill JG, Sebel PS, Blackburn CL, Heykants J. Linearity of pharmacokinetics and model estimation of sufentanil. Anesthesiology. 1982;57:439\u0026ndash;443.\u003c/li\u003e\n\u003cli\u003eGepts E, Shafer SL, Camu F, Stanski DR, Whitwam JG, Van Peer A, Woestenborghs R, Heykants J, Lunn JK. Linearity of pharmacokinetics and model estimation of sufentanil. Anesthesiology. 1995;83:1194\u0026ndash;1204.\u003c/li\u003e\n\u003cli\u003eAbsalom AR, Glen JI, Zwart GJ, Schnider TW, Struys MM. Target-controlled infusion: a mature technology. Anesth Analg. 2016;122:70\u0026ndash;78.\u003c/li\u003e\n\u003cli\u003eHuang W, Wu F, Tian L, Xu C, Wang H. Clinical practice guidelines in adult diagnostic flexible bronchoscopy: systematic review of the literature and quality appraisal with AGREE II. J Thorac Dis. 2024;16(10):7111\u0026ndash;7122. doi:10.21037/jtd-24-773.\u003c/li\u003e\n\u003cli\u003eStolz D, Chhajed PN, Leuppi JD, Brutsche M, Pflimlin E, Tamm M. Cough suppression during flexible bronchoscopy using combined sedation with midazolam and hydrocodone: a randomised, double blind, placebo controlled trial. Thorax. 2004;59(9):773\u0026ndash;776.\u003c/li\u003e\n\u003cli\u003eWang L, Wu Q, Wang M, Ming W, Sheng C, Zhang Y, Chen Y, Cao Y. The safety and efficacy of alfentanil combined with midazolam in fiberoptic bronchoscopy sedation: a randomized, double-blind, controlled trial. Front Pharmacol. 2022;13:1036840.\u003c/li\u003e\n\u003cli\u003eContoli M, Lamberti G, Galeone C, Mattarelli M, Ronchi MC, Gatti R. Midazolam in flexible bronchoscopy premedication: effects on patient-related and procedure-related outcomes. J Bronchol Interv Pulmonol. 2013;20:232\u0026ndash;240.\u003c/li\u003e\n\u003cli\u003eZhang W, Yang YX, Yu W, Qi SH. Cough suppression during flexible bronchoscopy using transcutaneous electric acupoint stimulation: a randomized controlled study. Evid Based Complement Alternat Med. 2019;2019:5650413. doi:10.1155/2019/5650413.\u003c/li\u003e\n\u003cli\u003eLing IT, Piccolo F, Mulrennan SA, Phillips MJ. Posture influences patient cough rate, sedative requirement and comfort during bronchoscopy: an observational cohort study. Cough. 2011;7:9. doi:10.1186/1745-9974-7-9.\u003c/li\u003e\n\u003cli\u003eXu Q, Zou X, Wu J, Duan G, Lan H, Wang L. Low-dose alfentanil inhibits sufentanil-induced cough during anesthesia induction: a prospective, randomized, double-blind study. Drug Des Devel Ther. 2024;18:1603\u0026ndash;1612. doi:10.2147/DDDT.S464823.\u003c/li\u003e\n\u003cli\u003eScholz J, Steinfath M, Schulz M. Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil: an update. Clin Pharmacokinet. 1996;31(4):275\u0026ndash;292. doi:10.2165/00003088-199631040-00004.\u003c/li\u003e\n\u003cli\u003eOu Y, Feng M, Hu B, Dong Y. The impact of alfentanil supplementation on the sedation of bronchoscopy: a meta-analysis of randomized controlled trials. Medicine (Baltimore). 2022;101(31):e27401. doi:10.1097/MD.0000000000027401.\u003c/li\u003e\n\u003cli\u003eHsieh CH, Lin TY, Wang TY, Lu CC, Huang CJ, Lee TY. The safety and efficacy of alfentanil-based induction in bronchoscopy sedation: a randomized, double-blind, controlled trial. Medicine (Baltimore). 2016;95:e5101.\u003c/li\u003e\n\u003cli\u003eAhonen J, Olkkola KT, Hynynen M, Seppala T, Ikonen S, Jantti V, Remmerie B, Eye J, Kallio A. Comparison of alfentanil, fentanyl and sufentanil for total intravenous anaesthesia with propofol in patients undergoing coronary artery bypass surgery. Br J Anaesth. 2000;85:533\u0026ndash;540.\u003c/li\u003e\n\u003cli\u003eCuiabano IS, Naves RP, Diehl RBA. Comparison of the recovery profile of sufentanil and remifentanil in total intravenous anesthesia: a systematic review and meta-analysis of randomized controlled trials. Braz J Anesthesiol. 2025;75(1):844558. doi:10.1016/j.bjane.2024.844558.\u003c/li\u003e\n\u003cli\u003eShafer SL, Varvel JR. Pharmacokinetics, pharmacodynamics, and rational opioid selection. Anesthesiology. 1991;74(1):53\u0026ndash;63. doi:10.1097/00000542-199101000-00010.\u003c/li\u003e\n\u003cli\u003eSridharan K, Sivaramakrishnan G. Comparison of fentanyl, remifentanil, sufentanil and alfentanil in combination with propofol for general anesthesia: a systematic review and meta-analysis of randomized controlled trials. Curr Clin Pharmacol. 2019;14(2):116\u0026ndash;124. doi:10.2174/1567201816666190313160438.\u003c/li\u003e\n\u003cli\u003eKateliya R, Madhukant, Dubey M, Chandra S, Sahay N. Comparison of recovery profiles in target-controlled infusions (TCI) versus manually controlled infusions for total intravenous anesthesia (TIVA) in laparoscopic surgeries: a randomized controlled trial. J Anaesthesiol Clin Pharmacol. 2023;39(2):258\u0026ndash;263. doi:10.4103/joacp.joacp_396_21.\u003c/li\u003e\n\u003cli\u003eBidkar PU, Dey A, Chatterjee P, Ramadurai R, Joy JJ. Target-controlled infusion: past, present, and future. J Anaesthesiol Clin Pharmacol. 2024;40(3):371\u0026ndash;380. doi:10.4103/joacp.joacp_64_23.\u003c/li\u003e\n\u003cli\u003eRong LQ, Kamel MK, Rahouma M, Naik A, Anousheh R, Loarte PS, Pryor KO, Gaudino M, Girardi LN. High-dose versus low-dose opioid anesthesia in adult cardiac surgery: a meta-analysis. J Clin Anesth. 2019;57:57\u0026ndash;62.\u003c/li\u003e\n\u003cli\u003eMay AM, Kazakov J, Strohl KP. Predictors of intraprocedural respiratory bronchoscopy complications. J Bronchology Interv Pulmonol. 2020;27(2):135\u0026ndash;141. doi:10.1097/LBR.0000000000000619.\u003c/li\u003e\n\u003cli\u003eSigmond N, Baechtold M, Schumacher PM, Hartwich V, Schnider TW, Luginb\u0026uuml;hl M. Pharmacokinetic parameter sets of alfentanil revisited: optimal parameters for use in target controlled infusion and anaesthesia display systems. Br J Anaesth. 2013;111(2):197\u0026ndash;208. doi:10.1093/bja/aet049.\u003c/li\u003e\n\u003cli\u003ePotdar MP, Kamat LL, Save MP. Cost efficiency of target-controlled inhalational anesthesia. J Anaesthesiol Clin Pharmacol. 2014;30(2):222\u0026ndash;227. doi:10.4103/0970-9185.130026.\u003c/li\u003e\n\u003cli\u003eColt HG, Morris JF. Fiberoptic bronchoscopy without premedication: a retrospective study. Chest. 1990;98(6):1327\u0026ndash;1330.\u003c/li\u003e\n\u003cli\u003eDershwitz M, Rosow CE, DiBiase PM, Zaslavsky A. Comparison of the sedative effects of butorphanol and midazolam. Anesthesiology. 1991;74(4):717\u0026ndash;724.\u003c/li\u003e\n\u003cli\u003eHughes MA, Glass PS, Jacobs JR. Context-sensitive half-time in multicompartment pharmacokinetic models for intravenous anesthetic drugs. Anesthesiology. 1992;76(3):334\u0026ndash;341.\u003cbr\u003e \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Target-controlled infusion, alfentanil, sufentanil, flexible bronchoscopy, randomized controlled trial","lastPublishedDoi":"10.21203/rs.3.rs-7843053/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7843053/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOptimal anesthetic management during flexible bronchoscopy requires balancing sedation, safety, and procedural efficiency. Target-controlled infusion (TCI) systems offer precise drug delivery, but comparative data between opioids remain limited. This study compared the safety and efficacy of alfentanil versus sufentanil target-controlled infusion and conventional alfentanil bolus dosing during flexible bronchoscopy.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods\u003c/b\u003e\u003c/p\u003e\u003cp\u003eIn this prospective, randomized, double-blind trial, 90 patients scheduled for bronchoscopy were enrolled and 1:1:1 assigned to alfentanil TCI (35 ng/mL, Group A), sufentanil TCI (0.2 ng/mL, Group S), or alfentanil bolus (5 \u0026micro;g/kg, Group M). Primary outcomes included hemodynamic stability and cough frequency. Secondary outcomes encompassed timing, respiratory complications, additional medication requirements, and procedural quality.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults\u003c/b\u003e\u003c/p\u003e\u003cp\u003eBaseline demographics were well-balanced across groups (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Cough incidence was significantly lower in both alfentanil groups compared to sufentanil TCI (Group A: median 1 [IQR 1-1.25]; Group M: median 1 [IQR 1\u0026ndash;2] versus Group S: median 2 [IQR 1\u0026ndash;3]; P\u0026thinsp;=\u0026thinsp;0.006). Hemodynamic parameters showed time-dependent differences between groups, with significant variations in heart rate and diastolic blood pressure at several time points, though all values remained within clinically acceptable ranges. Induction time was significantly shorter with alfentanil TCI versus other groups (Group A: 2 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] minutes versus Group S and M: 3 [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and 3 [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] minutes, respectively; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Awakening time demonstrated marked differences, with alfentanil bolus providing the fastest recovery (Group M: 7.5 [\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] minutes versus Group A: 10 [8.75-12] minutes versus Group S: 19 [14.25-22] minutes; P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant differences were observed in respiratory depression rates, additional propofol needs, or bronchoscopist satisfaction scores between groups.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAlfentanil regimens provided superior cough suppression compared to sufentanil. Alfentanil TCI offered the fastest induction, while bolus dosing enabled the quickest recovery. Both demonstrated favorable safety, supporting alfentanil as the preferred opioid for flexible bronchoscopy, with regimen choice guided by clinical priorities.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTrial Registration\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThis trial was retrospectively registered in the Chinese Clinical Trial Registry (ChiCTR2400089901) on September 19, 2024.\u003c/p\u003e","manuscriptTitle":"Safety and Efficacy of Alfentanil Compared to Sufentanil in Target- Controlled Infusion During Flexible Bronchoscopy: A Randomized Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-19 11:57:46","doi":"10.21203/rs.3.rs-7843053/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-11-11T12:27:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"373116361774385398465192544223056150","date":"2025-11-10T10:25:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-10T06:59:13+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-05T04:26:58+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-10-16T16:46:17+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-10-16T03:04:31+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Anesthesiology","date":"2025-10-16T03:01:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-anesthesiology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bane","sideBox":"Learn more about [BMC Anesthesiology](http://bmcanesthesiol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bane","title":"BMC Anesthesiology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6eaf18d2-5faf-43eb-ba3d-ab11a80e86a8","owner":[],"postedDate":"November 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-11-19T11:57:46+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-19 11:57:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7843053","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7843053","identity":"rs-7843053","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}