Combination of Sufentanil and Topiramate with Propofol for Sedation in Patients Undergoing Gastroscopy and Reducing Allergic Response

Summary

This protocol aims to enhance sedation safety and efficacy during gastroscopy by combining propofol with sufentanil and topiramate, resulting in reduced drug dosage, fewer adverse effects, improved hemodynamic stability, faster recovery, and greater patient and clinician satisfaction.

Abstract

Propofol is widely used for sedation in upper gastrointestinal endoscopy but is associated with dose-dependent adverse effects such as hypotension, respiratory depression, and delayed recovery. This study evaluated the efficacy and safety of combining sufentanil and topiramate with propofol compared to propofol alone for procedural sedation during elective gastroscopy. In this prospective, randomized, double-blind clinical trial, 120 adult patients scheduled for elective upper gastrointestinal endoscopy were allocated to either a combination group (sufentanil + topiramate + propofol) or a control group (propofol only). Hemodynamic and respiratory parameters, total propofol dose, sedation depth, recovery time, adverse events, and patient and endoscopist satisfaction were recorded and compared between groups. The combination group required significantly lower total propofol doses and demonstrated improved hemodynamic stability, higher oxygen saturation, and shorter procedure and recovery times (p < 0.05 for all). The incidence of hypoxemia, hypotension, nausea, and other sedation-related complications was markedly reduced. Cognitive recovery and readiness for discharge were achieved faster in the combination group. Both patient and endoscopist satisfaction scores were significantly higher, reflecting smoother procedural conditions and greater overall comfort. The multimodal sedation regimen combining sufentanil and topiramate with propofol provides superior procedural safety, enhanced hemodynamic and respiratory stability, faster recovery, and greater satisfaction compared to propofol monotherapy. These findings support the adoption of this protocol as a safe and effective alternative for routine sedation in gastroscopy.

Introduction

Gastroscopy is an essential diagnostic and therapeutic procedure for evaluating and managing upper gastrointestinal disorders, providing direct visualization of mucosal surfaces and facilitating early intervention. However, the procedure can cause discomfort, anxiety, and gag reflexes, often compromising patient tolerance and procedural success; hence, adequate sedation is crucial to ensure patient comfort and safety during the examination¹. Propofol remains the preferred sedative agent due to its rapid onset, short duration of action, and predictable hemodynamic profile². Despite these advantages, propofol monotherapy may lead to adverse effects such as respiratory depression, hypotension, and bradycardia, particularly at higher doses. To minimize these risks, adjunctive agents such as sufentanil, a potent synthetic opioid analgesic, are often co-administered to lower the propofol requirement while maintaining adequate sedation and analgesia³. Sufentanil acts primarily via µ-opioid receptor activation, producing effective analgesia at lower doses than other opioids and releasing minimal histamine, thereby reducing vasodilation and allergic responses⁴. When combined with propofol, sufentanil enhances sedation quality, stabilizes hemodynamics, and reduces respiratory depression^5,6. Its pharmacokinetic characteristics-rapid onset, predictable dose-response curve, and short context-sensitive half-life-make it ideal for outpatient procedures^7,8. This combination also suppresses cough and gag reflexes, improving procedural efficiency and operator satisfaction^9,10. Additionally, sufentanil has been reported to attenuate cardiovascular fluctuations during endoscope insertion, offering particular benefits to patients with cardiovascular comorbidities^11,12. Clinical trials confirm that the sufentanil-propofol regimen yields faster recovery and lower postoperative nausea and vomiting rates compared with propofol alone^{13,14,15,16,17}. While the propofol-sufentanil regimen provides balanced sedation, incorporating topiramate introduces a novel multimodal approach targeting both inflammatory and allergic pathways. Topiramate, an antiepileptic drug with recognized neuroprotective, anti-inflammatory, and immunomodulatory properties, reduces the release of pro-inflammatory cytokines such as IL-1β and TNF-α, potentially lowering hypersensitivity during sedation^{18,19,20,21,22}. Its addition permits smaller doses of both propofol and sufentanil, minimizing dose-related adverse effects while maintaining sedation depth and cardiovascular stability^23,24,25.

The propofol-sufentanil-topiramate combination thus represents a rational multimodal sedation strategy in which each agent contributes synergistically: propofol ensures rapid hypnosis, sufentanil provides potent analgesia and hemodynamic control, and topiramate mitigates allergic and inflammatory responses. This synergy produces uniform sedation depth, fewer intra-procedural interruptions, and shorter recovery times-advantages especially valuable in outpatient endoscopy^26,27,28. Emerging evidence further indicates that topiramate blunts stress-induced cortisol release and oxidative damage, improving recovery and neurocognitive outcomes^{29,30,31,32,33}. Multimodal regimens also appear to prevent opioid- or propofol-induced hyperalgesia and postoperative nausea, enhancing patient comfort^{34,35,36,37,38}. Notably, adjunctive topiramate may safeguard against sedation-related cognitive decline, particularly in elderly or neurologically vulnerable populations^39,40,41. Moreover, consistent pharmacokinetic and pharmacodynamic profiles of this triple-drug combination enhance clinician satisfaction and procedural efficiency^42,43,44. Topiramate's anti-inflammatory and immunomodulatory effects additionally reduce the risk of allergic manifestations, airway reactivity, and hemodynamic instability during and after sedation^{45,46,47,48,49,50,51}. Preliminary data suggest that this combination maintains cardiovascular stability, likely through topiramate's mild vasodilatory and immunosuppressive properties⁵¹.

In summary, the propofol-sufentanil-topiramate regimen offers a synergistic, safe, and effective sedation protocol for gastroscopy. By reducing total drug doses, improving hemodynamic stability, attenuating inflammatory and allergic responses, and promoting faster cognitive recovery, it enhances procedural success and patient outcomes. Further multicenter randomized trials are warranted to optimize dosage, confirm long-term safety, and establish standardized guidelines for its broader clinical application.

Protocol

This was a prospective, randomized, double-blind, controlled clinical trial conducted in the Department of Anesthesiology, Tongling Municipal Hospital, Anhui Province, China, between January 2022 and January 2024. The trial followed the CONSORT guidelines for randomized studies and adhered to the principles of the Declaration of Helsinki (2013 revision). The study protocol was approved by the Ethics Committee of Tongling Municipal Hospital (Approval No. 2023KY-105). Written informed consent was obtained from all participants prior to enrollment.

Sample size and power calculation

An a priori sample size estimation was performed using G*Power version 3.1.9.7 to ensure adequate statistical power for detecting the primary outcome - the difference in total propofol dose between the combination and control groups. Assumptions for the calculation were derived from pilot data and previously published studies^7,15.

Expected reduction in propofol dosage: 20-25%

Effect size (Cohen's d): 0.6

α (Type I error): 0.05 (two-tailed)

β (Type II error): 0.20 (80% power)

Allocation ratio: 1:1

Under these parameters, a minimum of 52 patients per group was required. To account for a 10%-15% attrition rate, 60 patients were recruited per group (total n = 120).

Participant selection

Participants were included based on the following criteria: Adults aged 18-70 years, ASA physical status I-III, scheduled for elective diagnostic or therapeutic upper gastrointestinal endoscopy under sedation, and provided written informed consent. Participants were excluded based on the following criteria: Known hypersensitivity to propofol, sufentanil, or topiramate, pregnant or lactating women, history of epilepsy, psychiatric disorder, or chronic central nervous system disease, severe cardiopulmonary or renal dysfunction, use of sedatives, opioids, or antiepileptics within 72 h before procedure, history of alcohol or substance abuse.

Randomization and allocation concealment

Participants were randomly assigned (1:1) to either the combination group (sufentanil + topiramate + propofol) or the control group (propofol only) using a computer-generated block randomization sequence (block size = 4) prepared by an independent biostatistician. Allocation concealment was maintained using opaque, sequentially numbered, and sealed envelopes that were opened by the attending nurse immediately before drug preparation.

Blinding procedures

Double-blind design: Both participants and endoscopists were blinded to group allocation.

Drug preparation: A dedicated anesthesiologist (not involved in data collection) prepared all medications in identical syringes.

Outcome assessment: Investigators recording intra- and post-procedure outcomes, as well as data analysts, remained blinded to group assignments.

Outcome measures

Primary outcome: Total propofol dosage (mg/kg) administered during the procedure was noted.

Secondary outcomes: The quality of sedation was assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scale. Patient comfort was rated post-procedure on a 0-10 visual analog scale. Hemodynamic stability was monitored via heart rate, systolic/diastolic blood pressure, and mean arterial pressure at 3 min intervals. Respiratory stability was evaluated by oxygen saturation (SpO₂) and respiratory rate (breaths/min). Procedure duration was measured as the time from endoscope insertion to withdrawal. Recovery time was measured as the time to achieve full orientation (MOAA/S = 5) and discharge readiness. Cognitive function was evaluated using the Mini-Mental State Examination (MMSE) 30 min post-procedure. Analgesic efficacy was assessed by pain intensity measured using the Numeric Rating Scale (NRS, 0-10) at discharge. Adverse events such as Hypoxemia (SpO₂ < 90%), hypotension, bradycardia, nausea, vomiting, or paradoxical agitation were noted as per occurrence. Allergic reactions were defined as the occurrence of rash, erythema, wheezing, edema, or anaphylaxis during or shortly after the procedure. Endoscopist satisfaction was rated on a 5-point Likert scale (1 = very dissatisfied to 5 = very satisfied). Post-procedural nausea and vomiting (PONV) were recorded during a 2 h observation window. Memory recall was determined using a standardized post-recovery interview.

Treatment procedure

All participants followed standard pre-anesthesia fasting guidelines: solids restricted for ≥6 h and clear fluids for ≤2 h before sedation. On arrival in the procedure room, baseline vital signs (blood pressure, heart rate, SpO₂, respiratory rate) were recorded, and standard monitoring was initiated, including noninvasive blood pressure, pulse oximetry, and three-lead ECG.

During gastroscopy, patients were placed in the left lateral decubitus position. Sedation was titrated to maintain MOAA/S scores between 1 and 2. Oxygen was administered via nasal cannula (2-4 L/min) to maintain SpO₂≥ 92%. Continuous intra-procedural monitoring was performed by an anesthesiologist and an endoscopist team.

Hemodynamic parameters (HR, SBP, DBP, MAP) were recorded every 3 min. Hypotension (SBP < 90 mmHg), bradycardia (HR < 50 bpm), or hypoxemia (SpO₂ < 90%) were managed according to institutional protocols (fluid bolus, atropine 0.3-0.5 mg, or supplemental oxygen). Additional propofol boluses (10-20 mg) were administered if patient movement, coughing, or gagging occurred.

Intervention protocol (Figure 1)

In the combination group (n = 60), oral topiramate 25 mg was administered approximately 10-12 h prior to the procedure (evening before). Intravenous sufentanil 0.1 µg/kg was administered immediately before sedation. Intravenous propofol 1.5-2 mg/kg bolus was administered for induction of sedation, with additional boluses of 10-20 mg as required to maintain a target sedation level of MOAA/S 1-2.

In the control group (n = 60), intravenous propofol 1.5-2 mg/kg bolus was given for sedation without pre-administration of topiramate or sufentanil. Supplemental propofol boluses (10-20 mg) as needed were given to maintain MOAA/S 1-2.

Post-procedure monitoring

After endoscope withdrawal, sedation was discontinued, and patients were transferred to the recovery area in a semi-recumbent position. Continuous monitoring was maintained for 2 h by trained nurses under an anesthesiologist's supervision. Vital signs (MAP, HR, SpO₂) and sedation depth (MOAA/S) were recorded every 10 min for the 1^st hour and every 30 min thereafter.

Pain (NRS), cognitive status (MMSE), and allergic reactions were assessed by a blinded examiner. Adverse events such as rash, itching, bronchospasm, or anaphylaxis were managed with standard therapies (antihistamines, corticosteroids, epinephrine as indicated). Time to recover (MOAA/S = 5) and discharge readiness were documented.

Patients were contacted 24 h post-procedure to record delayed adverse effects (nausea, dizziness, or allergic symptoms). All data, including sedative dosage, procedure time, adverse events, and recovery time, were collected for analysis (see Table 1, Table 2).

Statistical analysis

All statistical analyses were performed using IBM SPSS Statistics, version 25.0. A two-tailed p < 0.05 was considered statistically significant for all tests. The normality of continuous variables was assessed using the Shapiro-Wilk test and visual inspection of histograms and Q-Q plots. Levene's test was applied to verify the homogeneity of variances before selecting parametric procedures.

For normally distributed data with equal variances, parametric tests were applied (independent-samples t-test, paired t-test, one-way ANOVA, or repeated-measures ANOVA as appropriate). When normality or variance homogeneity assumptions were violated, non-parametric alternatives were used (Mann-Whitney U, Wilcoxon signed-rank, or Kruskal-Wallis tests).

Continuous variables (e.g., total propofol dose, recovery time, MMSE score) were summarized as mean ± SD and compared between groups using independent-samples t-tests or ANOVA. Categorical variables (e.g., incidence of adverse events, allergic reactions) were expressed as counts and percentages and analyzed using the Chi-square test or Fisher's exact test when expected frequencies were < 5. Time-dependent variables (heart rate, blood pressure, SpO₂) recorded at multiple intra-procedural time points were analyzed using repeated-measures ANOVA with Bonferroni correction for pairwise post-hoc comparisons.

To identify independent predictors of procedural outcomes (e.g., recovery time, cognitive function), a multiple linear regression model with backward stepwise elimination was employed. Variables with p < 0.10 in univariate analysis were entered into the multivariate model. Multicollinearity was evaluated using the variance inflation factor (VIF), with values < 5 indicating acceptable tolerance. Model adequacy was verified through residual plots and adjusted R².

Potential confounders age, BMI, ASA physical status, baseline anxiety score, and procedure duration were included in adjusted analyses. Effect sizes (Cohen's d for mean differences, η² for ANOVA) were calculated to quantify the magnitude of effects. Missing data was minimal (< 5%) and managed using listwise deletion; no imputation was performed. All statistical procedures adhered to recognized best practices for clinical trial data analysis.

Results

Demographic and baseline characteristics of patients

The various demographic and baseline parameters of the patients under the combination and control groups were similar and had no significant differences, meaning that baseline confounding factors could not skew study results (Table 3).

Intra-procedure parameters

The results for the intra-procedural phase revealed significant differences...

Discussion

This prospective randomized trial demonstrated that the combination of sufentanil and topiramate with propofol provides superior sedation quality, greater hemodynamic stability, faster recovery, and fewer adverse effects compared with propofol alone in patients undergoing diagnostic or therapeutic gastroscopy. Baseline demographic and clinical parameters were well matched between groups, minimizing confounding effects.

Hemodynamic and respiratory stability

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Endoscope System	Olympus Medical Systems	GIF-H190	Gastroscopy equipment for upper GI endoscopic procedures.
Mini Mental State Examination (MMSE) Kit	Psychological Assessment Resources	MMSE-KIT	Cognitive assessment tool used post-procedure.
Nasal Cannula (2-4 L/min O2 flow)	Teleflex Medical	1041-0-25	For supplemental oxygen delivery during and after the procedure.
Patient Monitor (BP, SpO2, ECG, HR)	Mindray	MEC-1200	For continuous intraoperative and recovery vital signs monitoring.
Propofol Injection (1%)	Fresenius Kabi	132419	Intravenous anesthetic agent used for sedation.
Pulse Oximeter	Philips	M1191B	To measure real-time oxygen saturation and pulse rate.
Sufentanil Citrate Injection (50 mcg/mL)	Yichang Humanwell Pharma	SFDA H20054137	Potent opioid analgesic used to reduce propofol requirements.
Syringe Pump	B. Braun	Infusomat Space	Controlled IV administration of sedatives and opioids.
Topiramate Tablets (25 mg)	Janssen Pharmaceuticals	NDC 50458-570-10	Oral anticonvulsant with neuroprotective and anti-inflammatory effects.