The median effective dose (ED50) of remimazolam combined with esketamine for conscious sedation in patients with dental anxiety undergoing outpatient dental surgery: a prospective, dose-finding study.
The ED50 provides a preliminary reference for initial dose selection in this clinical setting and requires validation in larger studies, but the wide confidence interval of the ED95 limits its clinical utility and requires validation in larger studies.
Abstract
Background
Dental anxiety presents a significant barrier to treatment. Conscious sedation is widely used to alleviate anxiety. Although remimazolam has demonstrated its efficacy and advantages for outpatient dental procedures, research on the effective dose of remimazolam combined with esketamine remains limited. Thus, the purpose of our research was to estimate the effective dose of remimazolam with esketamine for conscious sedation in patients with dental anxiety undergoing outpatient dental surgery.
Methods
The study enrolled outpatients with dental anxiety aged 18-65 years who received dental operations and were classified under ASA grades I-II. Using the modified Dixon up-and-down method, each patient was first administered by infusing esketamine 0.1 mg/kg, followed by an assigned dose of remimazolam. The initial dose of remimazolam was 0.1 mg/kg, with a dose gradient of 0.01 mg/kg. Sedation success was defined as achieving a MOAA/S score of 3-4 within 5 min after the initial loading dose, without requiring additional remimazolam. The primary outcome was the ED50 of remimazolam and its 95% confidence interval (CI). Secondary outcomes included security indicators, patient satisfaction and memory of the procedure, dentist satisfaction, duration of treatment, and discharge time.
Results
The study achieved 10 transition points (from sedation success to failure) with a total enrollment of 32 individuals. The ED50 and ED95 of remimazolam with 0.1 mg/kg esketamine, for conscious sedation during outpatient dental surgery, were 0.069 mg/kg (95% CI: 0.050-0.080 mg/kg) and 0.099 mg/kg (95% CI: 0.085-0.200 mg/kg), respectively. No circulatory and respiratory adverse events requiring intervention were observed during anesthesia induction.
Conclusions
For outpatient dental procedures in patients with dental anxiety, the ED50 and ED95 of remimazolam with esketamine for conscious sedation were 0.069 mg/kg and 0.099 mg/kg, respectively. The ED50 provides a preliminary reference for initial dose selection in this clinical setting. However, the wide confidence interval of the ED95 limits its clinical utility and requires validation in larger studies.
TRIAL REGISTRATION
This study was registered in the Chinese Clinical Trial Registry (ChiCTR2500104775; first registered on 23/06/2025).
Remimazolam significantly shortened recovery time and reduced flumazenil use in elderly patients, which may reduce staff workload after ERCP; larger studies are needed to establish comparative safety.
Suguru Ito, Y. Tanisaka, S. Ryozawa et al.· Scandinavian Journal of Gast...· 0 citations
To manage the behavior of the children with high levels of dental anxiety, the combination of inhalation sedation with intranasal midazolam can be efficiently used.
Background Propofol is the most frequently administered intravenous anesthetic in painless gastroscopy. Oliceridine, a novel μ-opioid receptor agonist, exhibits analgesic effects while reducing adverse reactions. The combination of propofol and oliceridine has shown promising efficacy in clinical practice. However, the exploration of the specific effective dosage of oliceridine in painless gastroscopy is still in its early stages. This study aimed to determine the median effective dose (ED₅₀) of oliceridine when combined with propofol during painless gastroscopy. Methods Patients aged 18–85 years with American Society of Anesthesiologists (ASA) physical status I to III undergoing painless gastroscopy were enrolled. They received an intravenous injection of oliceridine, followed by propofol at a dose of 1.5 mg/kg. The initial dose of oliceridine for the first patient was 20 μg/kg, and subsequent doses were adjusted using Dixon’s up-and-down method based on the previous patient’s response to gastroscope insertion—with a 1 μg/kg increase or decrease depending on the observed response. Data collection continued until 7 crossover points were obtained. Probit regression and bootstrapping methods were used to calculate the ED₅₀ and its 95% confidence intervals (CI). Hemodynamic parameters and perioperative adverse events were recorded. Results A total of 24 patients were included in the study. The ED₅₀ of oliceridine combined with propofol (1.5 mg/kg) for inhibiting the response to gastroscope insertion in patients undergoing painless gastroscopy was 19.33 μg/kg (95% CI, 17.41 ~ 21.98 μg/kg). The vital signs of all patients remained within the predefined acceptable limits, and no serious adverse events occurred. Conclusion The ED₅₀ of oliceridine combined with propofol (1.5 mg/kg) for inhibiting gastroscope insertion responses in adult patients undergoing painless gastroscopy is 19.33 μg/kg. Clinical trials registration ChiCTR2500105523.
Xiaojing Zhang, Weimin Qin, Xinying Zhang et al.· Frontiers in Medicine· 0 citations
: Background: Preoperative anxiety is a significant challenge in pediatric anaesthesia, necessitating effective premedication strategies. Oral drug combinations offer a non-invasive and child-friendly approach to achieving adequate sedation and anxiolysis. This study evaluates two commonly employed oral premedication regimens-ketamine combined with dexmedetomidine (KD) and ketamine combined with midazolam (KM) — in children aged 2 – 10 years scheduled for elective procedures. Methods: A prospective observational study was conducted at a tertiary care hospital over 14 months (March 2024 – May 2025). Sixty pediatric patients (ASA I – III, aged 2 – 10 years) were allocated into two groups of 30 each. Group KM received oral ketamine 3 mg/kg + midazolam 0.3 mg/kg, and Group KD received oral ketamine 3 mg/kg + dexmedetomidine 3 mcg/kg, each diluted in mango juice and administered 50 minutes before surgery. Sedation was assessed using the Modified Observer's Assessment of Alertness/Sedation (MOAAS) scale, parental separation anxiety score, mask acceptance scale, and hemodynamic parameters. Results: At the 50-minute time point, Group KD showed significantly deeper sedation (MOAAS: 2.1 ± 0.64) compared to Group KM (2.6 ± 0.60; p < 0.05). Parental separation was rated excellent in 90% of KD patients versus 56.7% in KM (p < 0.001). Mask acceptance was superior in KD (83.3% excellent) compared to KM (46.7% excellent; p = 0.006). Hemodynamic parameters remained clinically stable in both groups with no significant intergroup differences. No adverse events were recorded in either group. Conclusion: Both premedication regimens demonstrated acceptable sedative profiles; however, the ketamine-dexmedetomidine combination provided superior sedation depth, smoother parental separation, and better mask acceptance with a comparable safety profile. These findings support ketamine-dexmedetomidine as a preferred oral premedication option in pediatric patients undergoing elective surgery.
Neha D Pokar, Sarika Dhaduk· International Journal of Sci...· 0 citations
To ascertain the median effective dose (ED50) and 95% effective dose (ED95) of a combination of sufentanil and remimazolam for suppressing the tracheal intubation response in patients receiving general anesthesia and to assess the hemodynamic stability and incidence of adverse events related to this drug regimen, this prospective dose-finding study used Dixon’s up-and-down sequential method. Thirty-one patients scheduled for surgery under general anesthesia between October 2023 and December 2023 were assessed for eligibility; 7 were excluded, and 24 completed the dose-finding sequence and were analyzed (12 with a negative and 12 with a positive intubation response). Anesthesia was induced with remimazolam 0.35 mg/kg, followed by sufentanil at an initial dose of 0.4 µg/kg, with subsequent dose adjustments based on the intubation response. The primary endpoint was the ED50 of sufentanil, and secondary endpoints included hemodynamic indices and adverse events. The ED50 and ED95 of sufentanil required to suppress the tracheal intubation response were 0.358 µg/kg (95% confidence interval, 0.340–0.376 µg/kg) and 0.436 µg/kg (95% CI, 0.409–0.504 µg/kg), respectively. Heart rate did not differ significantly between response groups. Mean arterial pressure at T2 and the incidence of hypertension were higher in the positive-response group. When remimazolam 0.35 mg/kg was used for induction, the ED50 and ED95 of sufentanil for suppressing the tracheal intubation response were 0.358 and 0.436 µg/kg, respectively. These estimates should be interpreted within the study population and dose-finding design.
Qing-Cai Chen, Yalan Yong, Huanhuan Dai et al.· Medicine· 0 citations
OBJECTIVES
Remimazolam is an ultra-short-acting benzodiazepine with a shorter pharmacokinetic half-life than midazolam. This study compared the efficacy and safety of remimazolam and midazolam for sedation during endoscopic ultrasound-guided tissue acquisition (EUS-TA) in patients with solid pancreatic lesions.
METHODS AND PATIENTS
We retrospectively reviewed patients who underwent EUS-TA under remimazolam (August 2025-February 2026) or midazolam (January 2025-July 2025). The primary outcome was the time from procedure completion to patient awakening. Secondary outcomes included sedation success rate, time to sedation onset, total dose and number of doses, agitation requiring procedure interruption, flumazenil use, and sedation-related adverse events.
RESULTS
A total of 101 patients received remimazolam and 105 received midazolam. Median time from procedure completion to patient awakening was significantly shorter with remimazolam (2 min; interquartile range [IQR] 2-3) than with midazolam (4 min; IQR 3-5; P<0.01). The median total number of doses was higher with remimazolam (P<0.01), while flumazenil administration was significantly lower (P<0.01). Sedation success rate, time to sedation onset, agitation requiring procedure interruption, and adverse event rates did not differ significantly.
CONCLUSION
Remimazolam was associated with faster recovery and reduced flumazenil use, suggesting improved efficiency and safety in post-procedural monitoring, along with decreased staff workload after EUS-TA.
Y. Tanisaka, S. Ryozawa, M. Mizuide et al.· Pancreas· 0 citations