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This study employed probit regression analysis to determine the 90% effective dose (ED ) of oliceridine when combined with propofol for day-case hysteroscopy. 100 patients undergoing hysteroscopic surgery were randomized to receive intravenous oliceridine (0.01, 0.015, 0.02, 0.025, or 0.03 mg kg ) 3 minutes preoperatively. Propofol was administered intravenously at 2 mg kg induction and maintained at 6 mg kg h . Successful anesthesia was defined as absence of body movement during cervical dilation. Parameters recorded included the success rate, propofol consumption, total surgical duration, recovery time, postoperative pain, and adverse events. The ED of oliceridine for suppressing response to cervical dilation was 0.025 (95% confidence interval, CI, 0.020-0.050) mg kg . The incidence of propofol injection pain in the 0.01, 0.015, 0.02, 0.025, and 0.03 mg kg oliceridine groups (80%, 80%, 45%, 40%, and 30%, respectively) were significantly different (P = 0.001). There was no difference in the propofol requirements, time to anesthesia emergence, and visual analog scores(VAS) at 30 minutes postoperation among groups. No serious adverse events occurred in any patient. For healthy adult women undergoing day-case hysteroscopy, oliceridine 0.025 mg kg combined with propofol provides effective and safe anesthesia.

Background Tracheal intubation may cause significant hemodynamic responses. Many drugs have been shown to be effective in modifying these cardiovascular responses, including remifentanil, fentanyl, sufentanil, and alfentanil. However, the 90% effect-site concentration (EC90) of remifentanil required to control cardiovascular responses to tracheal intubation when combined with ciprofol remains unclear. The purpose of this study was to determine the EC90 of remifentanil inhibiting cardiovascular responses to tracheal intubation during anesthesia induction with ciprofol using biased-coin design up-and-down sequential method (BC-UDM). Methods This is a prospective sequential allocation dose-finding study. American Society of Anesthesiologists physical status (ASA) I–II elective surgical patients receiving target-controlled infusion (TCI) of remifentanil effect-site concentration (Ce), followed by ciprofol and rocuronium for anesthesia, were enrolled. The cardiovascular response to tracheal intubation was defined as positive when mean arterial pressure (MAP) or heart rate (HR) is 15% higher than the baseline value. Using the BC-UDM, the Ce of remifentanil was determined based on the cardiovascular response to tracheal intubation of the previous patient. The EC90 and 90% confidence intervals (90% CIs) were estimated by R-Foundation centered isotonic regression and the pooled adjacent violators algorithm with bootstrapping. Discussion The results of this study sought to demonstrate EC90 of remifentanil blunting sympathetic responses to tracheal intubation during anesthesia index (Ai)-guided ciprofol anesthesia using BCD-UDM. It may help to minimize the cardiovascular responses to tracheal intubation. Trial registration Chinese Clinical Trial Registry ChiCTR2300078275. Registered on December 3, 2023.

Background: Remimazolam is a good option for anesthesia in elderly patients undergoing gastrointestinal (GI) endoscopy procedures because of its rapid onset, short metabolic duration, and extensively documented safety profile. However, the accurate clinical dosage of these agents has yet to be determined. The objective of this research was to examine the efficacy of the 90% effective dose (ED90) of remimazolam in suppressing the responses of elderly patients during the insertion phase of upper GI endoscopy. Methods: We enrolled 53 individuals aged 65– 85 years who underwent upper GI endoscopy and were anesthetized with an intravenous bolus of remimazolam. After initiating an initial dose of 0.35 mg/kg remimazolam, subsequent adjustments were made on the basis of the patient’s response, employing an up‐and‐down sequential allocation using a biased coin design. The primary outcome was the ED90 of the remimazolam infusion for inhibiting the response to upper GI endoscope insertion. Adverse reactions during the perioperative period were observed and recorded. Results: The ED90 of remimazolam for upper GI endoscope insertion in elderly patients was 0.400 mg/kg (95% CI = 0.348–0.524). Stable circulation was maintained in all patients, and no serious adverse events were observed during sedation. Satisfaction levels were high among the participants: Patients reported a satisfaction score of 4.98 ± 0.14 points, anesthesiologists rated their satisfaction at 4.91 ± 0.35 points, and endoscopists expressed a satisfaction level of 4.89 ± 0.38 points (based on a total score of 5 points, with a minimum of 1 point). Conclusion: Administration of remimazolam for upper GI endoscopy in elderly patients was found to be both safe and effective. A single intravenous bolus at an ED90 dose of 0.556 mg/kg effectively suppressed the response to the procedure. Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2200062535

Remimazolam has shown safety and efficacy in providing sedation during gastroscopy, but research on its specific clinical dosage is limited. This study aimed to determine the 90% effective dose (ED 90 ) of remimazolam when used with a low dose of alfentanil for inducing sedation in adult patients undergoing gastroscopy. Fifty adult participants underwent upper gastrointestinal (GI) endoscopy with anesthesia via intravenous boluses of remimazolam and alfentanil (4 μg/kg). The initial remimazolam dose was 0.2 mg/kg, adjusted using the biased coin up‐and‐down (BCUD) sequential method. The ED 90 of remimazolam, administered with 4 μg/kg alfentanil, was found to be 0.2375 mg/kg (95% CI: 0.1500–0.2725). Hemodynamics remained stable, with no significant adverse events and high satisfaction scores from patients, anesthesiologists, and endoscopists (4.90 ± 0.043, 4.92 ± 0.039, and 4.92 ± 0.039, respectively, on a 5‐point scale). The combination of remimazolam and low‐dose alfentanil is safe and effective for adult upper GI endoscopy. Trial Registration: Chinese Registry of Clinical Trials: ChiCTR2200062535

Remimazolam is widely employed in surgical abortions. However, its dosing references from clinical studies such as gastrointestinal and bronchoscopic anesthesia have resulted in high incidence of physical movement. Determining the optimal dosage (the 90% effective dose [ED90]) for preventing physical movement during surgical abortions. Fifty-seven individuals aged 18 to 45 undergoing surgical abortion were included. Remimazolam, combined with remifentanil, was utilized for anesthesia induction. Commencing at an initial dose of 0.25 mg/kg of remimazolam, subsequent adjustments relied on the preceding patient's response, employing an up-down sequential allocation utilizing a biased-coin design. Patients received remimazolam doses ranging from 0.25 to 0.65 mg/kg. The estimated ED90, along with its 95% confidence interval (CI), for preventing physical movement was 0.615 mg/kg (0.398-0.629 mg/kg). Patients maintained stable circulation, and no significant adverse events were recorded. Patients reported a satisfaction score of 4.63 ± 0.62 points. Anesthesiologists rated their satisfaction at 4.19 ± 0.61 points, and endoscopists expressed a satisfaction level of 4.53 ± 0.57 points (based on a full score of 5 points, with a minimum of 1 point). The ED90 of remimazolam during surgical abortion to prevent physical movement was determined to be 0.615 mg/kg (95% CI, 0.398-0.629 mg/kg).

Background Compared to midazolam, remimazolam has a faster onset and offset of hypnotic effect, as well as cardiorespiratory stability, this study aims to determine the 90% effective dose (ED90) of remimazolam to inhibit responses to insertion of a duodenoscope during endoscopic retrograde cholangiopancreatography (ERCP). Methods A dose-response study was carried out undergoing ERCP who received remimazolam-alfentanil anesthesia using 10 µg/kg of alfentanil between September 2021 and November 2021. The initial dose of remimazolam was 0.2 mg/kg. The dose was then decided based on the responses of earlier patients by exploiting the sequential ascend and descend according to a 9: 1 biased coin design. Upon failure, the dose of remimazolam was increased by 0.025 mg/kg in the next patient. When the insertion was successful, the succeeding patient was randomized to an identical dose or a dose that was lower by 0.025 mg/kg.The ED90 of remimazolam for inhibiting responses to the insertion of a duodenoscope during ERCP was calculated. Adverse events and complications of remimazolam were recorded. Results A total of 55 elderly patients (age > 65) were included in the study. 45 successfully anesthetized patients, and 10 unsuccessfully. The ED90 of remimazolam was 0.300 mg/kg (95% CI = 0.287–0.320). ED95 was 0.315 (95% CI = 0.312–0.323) and ED99 was 0.323 (95% CI = 0.323–0.325). Among the patients, 9 patients developed hypotension, 2 patients developed bradycardia and 1 patient developed tachycardia, and hypoxia occurred in 2 patients. Conclusions A loading dose of 0.300 mg / kg of remimazolam for elderly patients undergoing ERCP can safely, effectively, and quickly induce patients to fall asleep and inhibit responses to the insertion of a duodenoscope. Trial registration The study protocol was registered at the website ClinicalTrials.gov on 22/09/2021(NCT05053763).

Background Esketamine and remimazolam co-administration presents a viable opioid-free anesthetic alternative for outpatient hysteroscopy. This study was designed to ascertain the ED 90 of esketamine for inhibiting intraoperative movement responses in patients undergoing ambulatory hysteroscopy. Methods From February 2024 to May 2024, 50 patients undergoing ambulatory hysteroscopy were enrolled. An anesthetic regimen combining esketamine and remimazolam with 50 mg flurbiprofen axetil was employed. The initial esketamine dose was 0.3 mg/kg, with subsequent doses determined using a biased-coin design (9:1). The primary endpoint was the ED 90 of esketamine for inhibiting movement responses. Secondary outcomes included anesthesia recovery time, Visual Analog Scale (VAS) scores, and adverse events. Results The ED 90 of esketamine was 0.405 mg/kg (95% CI: 0.370–0.494). Mean anesthesia recovery time was 12.1 ± 2.0 min. No respiratory depression, hypertension, hypotension, or bradycardia occurred. Mild dizziness was observed in 38% of patients; other adverse events (postoperative nausea and vomiting 4%, coughing 4%, hiccups 4%, transient diplopia 2%) resolved spontaneously. Postoperative VAS scores ranged from 0 to 4 at PACU admission (4% reporting 4), decreasing to 0–1 within four hours. Conclusions In ambulatory hysteroscopy under remimazolam-based anesthesia with preemptive analgesia using flurbiprofen axetil, the ED 90 of esketamine required to suppress intraoperative body movement was 0.405 mg/kg (95% CI: 0.370–0.494).

Objective This study aimed to determine the 90% effective dose of ciprofol combined with 5 µg of sufentanil for sedation during gastroscopy. Methods This was a double-blind, single-center dose-finding study. The ciprofol dose was assigned using a biased coin design according to the response of the previous patient, except for the first one, for which the dose was 0.3 mg/kg. All patients received 5 µg of sufentanil. The criterion for successful sedation was gastroscope insertion without choking, coughing, or body movement. If the sedation of the previous patient was unsuccessful, the dose for the next patient was increased by 0.05 mg/kg; if the sedation of the previous patient was successful, the next dose was reduced by 0.05 mg/kg or remained the same according to the biased coin result. The 90% effective dose was obtained using isotonic regression (the 95% confidence interval was obtained using the bootstrapping method) as the primary method, and the results were obtained using probit regression as a sensitivity analysis. Results Fifty-three patients were included in this study. Patients were assigned to one of four dose groups using a biased coin toss: group A (0.30 mg/kg), group B (0.35 mg/kg), group C (0.40 mg/kg) or group D (0.45 mg/kg). The 90% effective dose was 0.367 (95% CI: 0.344–0.416) mg/kg according to isotonic regression and 0.368 (95% CI: 0.347–0.419) mg/kg according to probit regression. The differences in the incidence of hypotension, mean arterial pressure and heart rate among the dose groups were not statistically significant. However, there was a statistically significant decrease in the mean arterial pressure and heart rate ( P  < 0.05) after the administration of ciprofol. Conclusion The 90% effective dose of ciprofol combined with 5 µg of sufentanil for sedation during gastroscopy was determined to be 0.367 (95% CI: 0.344–0.416) mg/kg. Within the dose range of 0.3–0.45 mg/kg, ciprofol reduced the mean arterial pressure and heart rate in patients, but these effects were not dose-dependent.

Oliceridine is a μ-opioid receptor agonist that selectively activates the G-protein signaling pathway, offering a potential advantage over traditional opioids by reducing respiratory depression and gastrointestinal reactions. This study aimed to determine the 90% effective dose (ED90) of oliceridine for inhibiting responses to laryngeal mask airway (LMA) insertion under etomidate anesthesia in patients of different ages. This prospective Biased-Coin Sequential Allocation Dose-Finding Trial initially enrolled 120 patients scheduled for LMA anesthesia, divided into two age groups: young-to-middle-aged (Group A, 18-64 years) and elderly (Group B, 65-79 years). The initial dose of oliceridine was 0.02 mg/kg, with dose spacing of 0.002 mg/kg. Dose adjustments for subsequent patients were based on the previous subject's response. If movement, frowning, tearing, coughing, or hemodynamic parameters exceeding 20% above baseline occurred during LMA insertion, the dose was considered inadequate, and the dose for the next patient was increased. Otherwise, biased-coin randomization was applied to the next patient, with an 89% probability of maintaining the same dose and an 11% probability of reducing the dose. The primary outcome was the ED90 and 95% confidence intervals (CIs) for oliceridine combined with etomidate in inhibiting responses to LMA insertion. A total of 113 patients met the study criteria and were included in the final analysis (58 in the group A and 55 in the group B). The ED90 of Oliceridine was 0.0246 mg/kg (95% CI: 0.0215-0.0320 mg/kg) and 0.0229 mg/kg (95% CI: 0.0199-0.0298 mg/kg), respectively. No significant difference in ED90 was observed between the two groups ( > 0.05). The ED90 of oliceridine for inhibiting LMA insertion responses, when combined with 0.25 mg/kg etomidate, was 0.0246 mg/kg in young-to-middle-aged patients and 0.0229 mg/kg in elderly patients. The study was registered with the Chinese Clinical Trial Registry (ChiCTR2500095893) on January 25, 2025.

BACKGROUND: The standard solutions for epidural labor analgesia include both local anesthetics and opioids. The concept of the standard epidural use of local anesthetics in labor analgesia has shifted from high concentrations to high volumes with low concentrations. However, the optimal dosage of opioids needed to initiate and maintain epidural labor analgesia in different phases during the first labor stage has rarely been studied. OBJECTIVE: The present study aimed to determine the optimal sufentanil dose for epidural initiation in the latent and active phases during the first stage of labor. STUDY DESIGN: A prospective, double-blind, sequential dose-finding study. SETTING: A Class A tertiary obstetrics and gynecology hospital. METHODS: The study included 80 nulliparae with cervical dilatation of 2-4 cm and 5-6 cm, with 40 nulliparae in each group. A research dose of sufentanil combined with ropivacaine 13 mg in epidural initiation with a volume of 15 mL was administered to the puerperant. A 1-microgram sufentanil dose and a 2.5-micrograms sufentanil dose were used for the first puerperant of each group. The dose of sufentanil for the subsequent puerperant was determined by the response of the previous puerperant according to the biased coin up-and-down design in each trial. The primary outcome was a visual analog scale score of <= 3 at 15, 30, and 45 minutes after epidural administration, including the given dose of sufentanil. According to the response of each puerperant, the 90% effective doses and their 95% confidence intervals were estimated by isotonic regression and bootstrapping according to the response of each puerperant. RESULTS: The 90% effective doses of sufentanil for puerperants were 1.91 micrograms (95% confidence intervals 1.82-2.35 micrograms) and 4.90 micrograms (95% confidence intervals 4.82-5.35 micrograms) in epidural initiation in the latent and active phases, respectively. The 90% effective doses were 62.5% (95% confidence intervals 50.8-64.0%) lower in the latent phase than that in the active phase during the first stage of labor. LIMITATIONS: Both spontaneous labor and induced labor were included in this study, and the degree of pain in these 2 types of labor is different. Further, only nulliparae were recruited in the study. CONCLUSIONS: Different sufentanil doses should be adopted in epidural initiation in different phases during the first stage of labor due to the large differences in the demand for sufentanil. KEY WORDS: Sufentanil, 90% effective dose, epidural initiation, labor analgesia, active phase, latent phase, first labor stage