Comparison of the efficacy and safety of ciprofol and propofol in sedating patients in the operating room and outside the operating room: a meta-analysis and systematic review.

BACKGROUND: As a new type of intravenous anesthetic, ciprofol has the advantages of fast onset of action, fast recovery and high clearance rate. This study aimed to investigate the effectiveness and safety of ciprofol versus traditional propofol for anesthesia and sedation in and out of the operating room. METHODS: We searched the literature in PubMed, Web of Science, Cochrane Library, and Embase databases from January 2021 to December 2023. All clinical studies comparing the sedative effects of propofol and ciprofol, both inside and outside the operating room, were included in our trial. The main outcome measures were induction time and incidence of injection-site pain. Data are merged using risk ratio and standardized mean difference with 95% confidence interval. Subgroup analysis, meta-regression, sensitivity analysis, and publication bias were performed. The study protocol was prospectively registered with PROSPERO (CRD42023447747). RESULTS: A total of 15 randomized, controlled trials involving 2002 patients were included in this study. Compared with propofol, ciprofol has a longer induction time in the operating room but a shorter induction time in non-operating room settings. Ciprofol can effectively reduce the risk of injection-site pain and respiratory depression both inside and outside the operating room. In addition, the risk of drug-related hypotension induced with ciprofol in the operating room is lower, but the awakening time is also longer. Meta-regression analysis showed that neither age nor BMI were potential sources of heterogeneity. Funnel plot, egger and begg tests showed no significant publication bias. Sensitivity analyzes indicate that our results are robust and reliable. CONCLUSION: Ciprofol has absolute advantages in reducing the risk of injection-site pain and respiratory depression, both in and outside operating room. Intraoperative use of ciprofol reduces the risk of drug-related hypotension and may also reduce the risk of intraoperative physical movements. However, ciprofol may have longer induction and awakening time than propofol.

Comparison of Ciprofol-Based and Propofol-Based Total Intravenous Anesthesia on Microvascular Decompression of Facial Nerve with Neurophysiological Monitoring: A Randomized Non-Inferiority Trial.

Purpose: Ciprofol is a recently developed short-acting gamma-aminobutyric acid receptor agonist with a higher potency than that of propofol. As a new sedative drug, there are few clinical studies on ciprofol. We sought to examine the safety and efficacy of ciprofol use for general anesthesia in neurosurgical individuals undergoing neurosurgical surgery with intraoperative neurophysiological monitoring (IONM). Patients and Methods: This single-center, non-inferiority, single-blind, randomized controlled trial was conducted from September 13, 2022 to September 22, 2023. 120 patients undergoing elective microvascular decompression surgery (MVD) with IONM were randomly assigned to receive either ciprofol or propofol. The primary outcome of this study was the amplitude of intraoperative compound muscle action potential decline, and the secondary outcome included the indexes related to neurophysiological monitoring and anesthesia outcomes. Results: The mean values of the primary outcome in the ciprofol group and the propofol group were 64.7±44.1 and 53.4±35.4, respectively. Furthermore, the 95% confidence interval of the difference was -25.78 to 3.12, with the upper limit of the difference being lower than the non-inferiority boundary of 6.6. Ciprofol could achieve non-inferior effectiveness in comparison with propofol in IONM of MVD. The result during anesthesia induction showed that the magnitude of the blood pressure drop and the incidence of injection pain in the ciprofol group were significantly lower than those in the propofol group (P<0.05). The sedative drug and norepinephrine consumption in the ciprofol group was significantly lower than that in the propofol group (P<0.05). Conclusion: Ciprofol is not inferior to propofol in the effectiveness and safety of IONM and the surgical outcome. Concurrently, ciprofol is more conducive to reducing injection pain and improving hemodynamic stability, which may be more suitable for IONM-related surgery, and has a broad application prospect.

Effect of Ciprofol on Left Ventricular Myocardial Strain and Myocardial Work in Children Undergoing Cardiac Surgery: A Single-center Double-blind Randomized Noninferiority Study.

OBJECTIVE: The current work was designed to compare the effects of ciprofol and propofol on left ventricular systolic function and myocardial work by noninvasive speckle-tracking echocardiography in children undergoing surgical repair of atrial septal or ventricular septal defects. DESIGN: A single-center double-blind randomized noninferiority study was conducted. SETTING: The research occurred at a tertiary care center affiliated with Shanghai Jiao Tong University, China. PARTICIPANTS: One hundred and twelve children aged 1 month to 16 years undergoing atrial septal or ventricular septal defect surgery with cardiopulmonary bypass were included. INTERVENTIONS: One hundred and twelve children were allocated randomly to receive ciprofol (n = 67) or propofol (n = 45) in a 1.5:1 ratio. Ciprofol or propofol were intravenously infused at loading doses of 0.4 mg/kg or 2.0 mg/kg, respectively, over 30 seconds, depending on the physical condition of each patient. When the bispectral index was maintained between 45 and 55 after induction, transthoracic echocardiography, including apical two-chamber, three-chamber, and four-chamber views, were collected bedside. MEASUREMENTS AND MAIN RESULTS: Of the 112 patients enrolled, 104 completed the study. Global longitudinal strain in the ciprofol and propofol groups after anesthesia was -17.3% (95% confidence interval [CI] -18.0% to -16.6%) and -17.8% (95% CI -18.7 to -17.0%) in the full analysis set and -17.5% (95% CI -18.2% to -16.9%) and -17.8% (95% CI -18.7% to -17.0%) in the per-protocol set, respectively. The noninferiority margin was set at 2% and confirmed with a lower limit of two-sided 95% CI for the intergroup difference of 1.58% in the full analysis set and 1.34% in the per-protocol set. There were no significant differences between the groups in left ventricular systolic and diastolic function and myocardial work indices. Postoperative vasoactive-inotropic score, NT-proBNP, duration of mechanical ventilation, and the length of stay in the cardiac intensive care unit and hospital were also comparable between the two groups (all p > 0.05). CONCLUSIONS: Ciprofol did not show different effects on myocardial function and postoperative outcomes from propofol. Further, on the sensitive cardiac systole marker global longitudinal strain, ciprofol demonstrated noninferiority to propofol. Ciprofol might be an alternative solution for cardiac anesthesia in children with congestive heart disease with mild lesion.

ED50 of ciprofol combined with sufentanil for fiberoptic bronchoscopy of different patient populations with pulmonary tuberculosis.

BACKGROUND: Ciprofol is a promising sedative. This study aims to explore the median effective dose (ED50) of ciprofol in inhibiting responses to fiberoptic bronchoscopy in patients with pulmonary tuberculosis (PTB) of different genders and ages when combined with 0.15 µg/kg sufentanil, and to evaluate its efficacy and safety, providing a reference for the rational use of ciprofol in clinical practice. METHODS: PTB patients who underwent bronchoscopy examination and treatment at The Third People's Hospital of Changzhou between May 2023 and June 2023 were selected and divided into four groups using a stratified random method. All patients received intravenous injection of 0.15 µg/kg sufentanil followed by injection of the test dose of ciprofol according to Dixon's up-and-down method. The initial dose of ciprofol in all four groups was 0.4 mg/kg, with an adjacent ratio of 1:1.1. The next patient received a 10% increase in the dose of ciprofol if the previous patient in the same group experienced positive reactions such as choking cough, frowning, and body movements during the endoscopy. Otherwise, it was judged as a negative reaction, and the next patient received a 10% decrease in the dose of ciprofol. The transition from a positive reaction to a negative reaction was defined as a turning point, and the study of the group was terminated when seven turning points occurred. Hemodynamic parameters, oxygen saturation and adverse reactions were recorded at different time points in all groups. The Probit regression analysis method was used to calculate the ED50 of ciprofol in the four groups and compare between the groups. RESULTS: The ED50 of ciprofol combined with 0.15 µg/kg sufentanil for bronchoscopy in the four groups were 0.465 mg/kg, 0.433 mg/kg, 0.420 mg/kg and 0.396 mg/kg, respectively. CONCLUSION: The ED50 of ciprofol used for fiberoptic bronchoscopy varied among PTB patients of different genders and ages. TRIAL REGISTRATION: The Chinese Clinical Trial Registry, ChiCTR2300071508, Registered on 17 May 2023.

Influences of Propofol, Ciprofol and Remimazolam on Dreaming During Anesthesia for Gastrointestinal Endoscopy: A Randomized Double-Blind Parallel-Design Trial.

Purpose: To compare the influences of propofol, ciprofol and remimazolam on dreaming during painless gastrointestinal endoscopy. Methods: This study was a single-center, prospective, parallel-design, double-blind, randomized clinical trial. Between May 2023 and October 2023, patients undergoing elective painless gastrointestinal endoscopy were recruited and randomly allocated into one of the three groups. Demographic data, intraoperative information, incidence of dreaming, insufficient anesthesia and intraoperative awareness, type of dream, patient satisfaction score, adverse events, and improvement of sleep quality were collected. Results: The difference in incidence of dreaming among the three groups was not significant (33.33% vs 48.33% vs 41.67%, p=0.061). The number of patients with intraoperative hypotension in the propofol group was larger than that of the remimazolam group (32 vs 12, p=0.001). However, the cases of intraoperative hypotension between propofol group and ciprofol group or ciprofol group and remimazolam group were comparable (32 vs 22, p=0.122; 22 vs 12, p=0.064). The percentage of insufficient anesthesia between propofol group and remimazolam group was significant (13.33% vs 1.67%, p=0.001), while no statistical difference was detected between propofol group and remimazolam group or ciprofol group and remimazolam group (13.33% vs 5.00%, p=0.025; 5.00% vs 1.67%, p=0.150). The ability of propofol to improve sleep quality at 1st post-examination day was significantly better than that of remimazolam (86.21% vs 72.88%, p=0.015), while it was not significant between propofol group and ciprofol group or ciprofol group and remimazolam group (86.21% vs 80.36%, p=0.236; 72.88% vs. 72.88%, p=0.181). Incidence of intraoperative awareness, intraoperative hypoxia, type of dream, satisfaction score, adverse events during recovery, and sleep improvement on the 7th post-examination day was not significant among the groups. Conclusion: Anesthesia with propofol, ciprofol and remimazolam, respectively, for gastrointestinal endoscopy did not induce statistical difference in the incidence of dreaming, despite that all of them are more likely to induce pleasant dreams.

Efficacy and safety of ciprofol for sedation in outpatient gynecological procedures: a phase III multicenter randomized trial.

Objective: Ciprofol (also known as cipepofol and HSK3486), is a compound similar to propofol in chemical structure and hypnotic effect. Herein we evaluated the efficacy and safety of ciprofol for sedation in outpatient gynecological procedures. Methods: This phase III multicenter randomized trial with a non-inferiority design was conducted in nine tertiary hospitals. We enrolled 135 women aged 18-65 years who were scheduled for ambulatory gynecological procedures. Patients were randomly assigned to receive either ciprofol (0.4 mg/kg for induction and 0.2 mg/kg for maintenance) or propofol (2.0 mg/kg for induction and 1.0 mg/kg for maintenance) sedation in a 2:1 ratio. Patients and investigators for data collection and outcome assessment were blinded to study group assignments. The primary outcome was the success rate of sedation, defined as completion of procedure without remedial anesthetics. The non-inferiority margin was set at -8%. Secondary outcomes included time to successful induction, time to full awake, time to meet discharge criteria, and satisfaction with sedation assessed by patients and doctors. We also monitored occurrence of adverse events and injection pain. Results: A total of 135 patients were enrolled; 134 patients (90 patients received ciprofol sedation and 44 patients propofol sedation) were included in final intention-to-treat analysis. The success rates were both 100% in the two groups (rate difference, 0.0%; 95% CI, -4.1 to 8.0%), i.e., ciprofol was non-inferior to propofol. When compared with propofol sedation, patients given ciprofol required more time to reach successful induction (median difference [MD], 2 s; 95% CI, 1 to 7; p < 0.001), and required more time to reach full awake (MD, 2.3 min; 95% CI, 1.4 to 3.1; p < 0.001) and discharge criteria (MD, 2.3 min; 95% CI, 1.5 to 3.2; p < 0.001). Fewer patients in the ciprofol group were dissatisfied with sedation (relative risk, 0.21; 95% CI, 0.06 to 0.77; p = 0.024). Patients given ciprofol sedation had lower incidences of treat-emergent adverse events (34.4% [31/90] vs. 79.5% [35/44]; p < 0.001) and injection pain (6.7% [6/90] vs. 61.4% [27/44]; p < 0.001). Conclusion: Ciprofol for sedation in ambulatory gynecological procedures was non-inferior to propofol, with less adverse events and injection pain. Clinical trial registration: ClinicalTrials.gov, identifier NCT04958746.

Exploring Ciprofol Alternatives: A Comprehensive Review of Intravenous Anesthesia Options.

Ciprofol is a recently developed, short-acting γ-aminobutyric acid receptor agonist sedative that is more potent than propofol. Still, there have been few clinical studies of this agent to date. This review explores alternative intravenous anesthesia options to ciprofol, considering their pharmacology, clinical efficacy, safety profile, and practical considerations. While ciprofol offers advantages such as rapid onset and predictable offset, concerns regarding its safety profile and individual variability in response have prompted the search for alternatives. Propofol, etomidate, ketamine, and dexmedetomidine are discussed as established options, each with unique characteristics and potential benefits. Emerging agents, including remimazolam, sufentanil, alfaxalone, and brexanolone, are examined for their potential role in anesthesia management. Recommendations for future research include large-scale comparative studies, optimization of dosing strategies, and personalized approaches guided by pharmacogenomic insights. Ultimately, the future of intravenous anesthesia lies in a multifaceted approach that integrates evidence-based practices, technological innovations, and individualized patient care to enhance safety, efficacy, and patient satisfaction across the perioperative continuum. Collaboration among stakeholders will be crucial in advancing the field and shaping the future landscape of intravenous anesthesia options.

Effect of propofol and ciprofol on the euphoric reaction in patients with painless gastroscopy: A prospective randomized controlled trial.

Objective: To explore the effects of propofol and ciprofol on patient euphoric reactions during sedation in patients undergoing gastroscopy and to investigate potential factors that may influence euphoric reactions in patients. Methods: A total of 217 patients were randomly divided into two groups: the propofol group (P group, n = 109) and the ciprofol group (C group, n = 108). The patients in the P group were given 2 mg/kg propofol, and those in the C group were given 0.5 mg/kg ciprofol. The patients were assessed using the Addiction Research Center Inventory-Chinese Version (ARCI-CV) to measure euphoric reactions at three time points: preexamination, 30 min after awakening, and 1 week after examination. Anxiety, depression, and sleep status were evaluated using appropriate scales at admission and 1 week after the examination. The dream rate, sedative effects, vital sign dynamics, and adverse reactions were documented during the sedation process. Results: After 30 min of awakening, the P group and C group showed no statistically significant differences in the mean morphine-benzedrine group (MBG) score (8.84 vs. 9.09, P > 0.05), dream rate (42.2 % vs. 40.7 %, P > 0.05), or MBG score one week after the examination (7.04 vs. 7.05, P > 0.05). The regression analysis revealed that sex, dream status, Alcohol Use Disorders Identification Test (AUDIT) score, and examination time had notable impacts on the MBG-30 min score. No statistically significant differences were observed in sedative effects, anxiety, depression, or sleep status between the two groups (P > 0.05). The incidence of injection pain and severe hypotension was significantly lower in the C group (P < 0.05), and hemodynamics and SpO2 were more stable during sedation (P < 0.05). Conclusion: There was no significant difference between propofol and ciprofol in terms of euphoria experienced by patients after sedation in patients undergoing gastroscopy. Ciprofol has demonstrated addictive potential similar to that of propofol, warranting careful attention to its addictive potential during clinical application.

The efficacy and safety of ciprofol and propofol in patients undergoing colonoscopy: A double-blind, randomized, controlled trial.

STUDY OBJECTIVE: Propofol is a commonly utilized anesthetic for painless colonoscopy, but its usage is occasionally limited due to its potential side effects, including cardiopulmonary suppression and injection pain. To address this limitation, the novel compound ciprofol has been proposed as a possible alternative for propofol. This study sought to determine whether there are any differences in the safety and efficacy of propofol and ciprofol for painless colonoscopy. DESIGN: Randomized clinical trial. SETTING: Single-centre, class A tertiary hospital, November 2021 to November 2022. PATIENTS: Adult, American Society of Anesthesiologists Physical Status I to II and body mass index of 18 to 30 kg m-2 patients scheduled to undergo colonoscopy. INTERVENTIONS: Consecutive patients were randomly allocated in a 1:1 ratio to receive sedation for colonoscopy with ciprofol (group C) or propofol (group P). MEASUREMENTS: The primary outcome was the success rate of colonoscopy. The secondary outcomes were onset time of sedation, operation time, recovery time and discharge time, patients and endoscopists satisfaction, side effects (e.g. injection pain, myoclonus, drowsiness, dizziness, procedure recall, nausea and vomiting) and incidence rate of cardiopulmonary adverse events. MAIN RESULTS: No significant difference was found in the success rate of colonoscopy between the two groups (ciprofol 96.3% vs. propofol 97.6%; mean difference - 1.2%, 95% CI: -6.5% to 4.0%, P = 0.650). However, group C showed prolonged sedation (63.4 vs. 54.8 s, P < 0.001) and fully alert times (9 vs 8 min, P = 0.013), as well as reduced incidences of injection pain (0 vs. 40.2%, P < 0.001), respiratory depression (2.4% vs. 13.4%, P = 0.021) and hypotension (65.9% vs. 80.5%, P = 0.034). Patients satisfaction was also higher in Group C (10 vs 9, P < 0.001). CONCLUSIONS: Ciprofol can be used independently for colonoscopy. When comparing the sedation efficacy of ciprofol and propofol, a 0.4 mg kg-1 dose of ciprofol proved to be equal to a 2.0 mg kg-1 dose of propofol, with fewer side effects and greater patient satisfaction during the procedure.

Efficacy and safety of ciprofol versus propofol for induction and maintenance of general anesthesia: a systematic review and meta-analysis.

BACKGROUND: Propofol has been the gold standard for anesthesia induction and maintenance due to its rapid onset and favorable pharmacokinetic properties. However, the search for alternative agents with improved safety and efficacy has led to the emergence of ciprofol (HSK3486), a structural analog of propofol. This systematic review and meta-analysis aim to comprehensively assess the safety and efficacy of ciprofol compared to propofol for anesthesia induction and maintenance in adult patients undergoing surgical procedures. METHODS: This study included only double-arm RCTs in which participants were aged eighteen or older undergoing surgery. For the statistical analysis of the extracted data, we employed RevMan 5.4.1. RESULTS: Ciprofol demonstrated a promising trend of higher anesthesiologists' satisfaction during the induction phase (MD 0.14, 95%, CI - 0.28 to 0.56, p = 0.51), whereas Propofol was favored during maintenance. Propofol also exhibited advantages with a shorter time to successful anesthesia induction (MD 0.08 min, 95% CI 0.00 to 0.15, p = 0.04), and quicker attainment of full alertness (MD 0.11 min, 95% CI - 1.29 to 1.52, p = 0.87), suggesting its efficiency in clinical practice. Importantly, there were no significant disparities in the success rate of anesthesia. CONCLUSION: Both ciprofol and propofol demonstrate comparable efficacy and safety for anesthesia induction and maintenance in adult patients undergoing surgery. While propofol provides a faster onset of induction, ciprofol exhibits advantages in terms of pain management. Clinicians should consider these findings when selecting anesthetic agents, and tailoring choices to individual patient needs and clinical scenarios.

Ciprofol ameliorates ECS-induced learning and memory impairment by modulating aerobic glycolysis in the hippocampus of depressive-like rats.

Electroconvulsive shock (ECS) is utilized to treat depression but may cause learning/memory impairments, which may be ameliorated by anesthetics through the modulation of hippocampal synaptic plasticity. Given that synaptic plasticity is governed by aerobic glycolysis, it remains unclear whether anesthetics modulate aerobic glycolysis to enhance learning and memory function. Depression-like behavior in rats was induced by chronic mild unpredictable stress (CUMS), with anhedonia assessed via sucrose preference test (SPT). Depressive-like behaviors and spatial learning/memory were assessed with forced swim test (FST), open field test (OFT), and Morris water maze (MWM) test. Changes in aerobic glycolysis and synaptic plasticity in the hippocampal region of depressive-like rats post-ECS were documented using immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy. Both the OFT and FST indicated that ECS was effective in alleviating depressive-like behaviors. The MWM test demonstrated that anesthetics were capable of attenuating ECS-induced learning and memory deficits. Immunofluorescence analysis, Western blot, Lactate Assay Kit and transmission electron microscopy revealed that the decline in learning and memory abilities in ECS-induced depressive-like rats was correlated with decreased aerobic glycolysis, and that the additional use of ciprofol or propofol ameliorated these alterations. Adding the glycolysis inhibitor 2-DG diminished the ameliorative effects of the anesthetic. No significant difference was observed between ciprofol and propofol in enhancing aerobic glycolysis in astrocytes and synaptic plasticity after ECS. These findings may contribute to understanding the mechanisms by which anesthetic drugs modulate learning and memory impairment after ECS in depressive-like behavior rats.

Median Effective Dose of Ciprofol Combined With Sufentanil for Inhibiting the Upper Gastrointestinal Endoscopic Placement Reaction in Elderly Patients.

Objective: Ciprofol is a new sedative anesthetic drug that can be used for gastrointestinal endoscopy and induction of general anesthesia, but the appropriate dosage for use in elderly patients has not been determined. Sufentanil is a commonly used opioid in clinical practice, and this study was designed to induce anesthesia in elderly patients using sufentanil in combination with ciprofol. However, the optimal dosage of ciprofol when it is co-administered with sufentanil has not yet been established. This study was designed to find the median effective dose (ED50) and 95% confidence interval (95% CI) of ciprofol for intravenous anesthesia when combined with sufentanil. Methods: We studied 57 patients who were scheduled to undergo a diagnostic upper gastrointestinal endoscopy. According to age, it was divided into two groups: 65∼74 years old (group A) and over 75 years old (group B). Using the modified Dixon sequence test method, intravenous bolus of 0.1 µg/kg sufentanil was given 3 min before ciprofol is administered, the initial dose of ciprofol was 0.4 mg/kg, the upper gastrointestinal endoscopy was placed after reaching the depth of sedation, and vital signs and adverse events were recorded at each perioperative time point (T0-T7). Results: In the group A, when combined with 0.1 µg/kg sufentanil, the ED50 of ciprofol to inhibiting responses to insertion of upper gastrointestinal endoscopy was 0.23 mg/kg, and the 95% CI was 0.09∼0.30 mg/kg; in the group B, the ED50 was 0.18 mg/kg, and the 95% CI was 0.13∼0.22 mg/kg. Conclusion: The ED50 of ciprofol in combination with sufentanil (0.1 µg/kg) for upper gastrointestinal endoscopy in elderly patients: 0.23 mg/kg in group A and 0.18 mg/kg in group B.

Exploring the Median Effective Dose of Ciprofol for Anesthesia Induction in Elderly Patients: Impact of Frailty on ED50.

Purpose: Explore the median effective dose of ciprofol for inducing loss of consciousness in elderly patients and investigate how frailty influences the ED50 of ciprofol in elderly patients. Patients and Methods: A total of 26 non-frail patients and 28 frail patients aged 65-78 years, with BMI ranging from 15 to 28 kg/m2, and classified as ASA grade II or III were selected. Patients were divided into two groups according to frailty: non-frail patients (CFS<4), frail patients (CFS≥4). With an initial dose of 0.3 mg/kg for elderly non-frail patients and 0.25 mg/kg for elderly frail patients, using the up-and-down Dixon method, and the next patient's dose was dependent on the previous patient's response. Demographic information, heart rate (HR), oxygen saturation (SpO2), mean blood pressure (MBP), and bispectral index (BIS) were recorded every 30 seconds, starting from the initiation of drug administration and continuing up to 3 minutes post-administration. Additionally, the total ciprofol dosage during induction, occurrences of hypotension, bradycardia, respiratory depression, and injection pain were recorded. Results: The calculated ED50 (95% confidence interval [CI]) and ED95 (95% CI) values for ciprofol-induced loss of consciousness were as follows: 0.267 mg/kg (95% CI 0.250-0.284) and 0.301 mg/kg (95% CI 0.284-0.397) for elderly non-frail patients; and 0.263 mg/kg (95% CI 0.244-0.281) and 0.302 mg/kg (95% CI 0.283-0.412) for elderly frail patients. Importantly, no patients reported intravenous injection pain, required treatment for hypotension, or experienced significant bradycardia. Conclusion: Frailty among elderly patients does not exert a notable impact on the median effective dose of ciprofol for anesthesia induction. Our findings suggest that anesthesiologists may forego the necessity of dosage adjustments when administering ciprofol for anesthesia induction in elderly frail patients.

Ciprofol alleviates remifentanil-induced hyperalgesia by regulating α2GABAARs, NR2B, and P-CaMKIIα levels in the spinal cord and hippocampus.

OBJECTIVES: Several studies have shown that propofol administration during surgery effectively attenuates remifentanil-induced hyperalgesia (RIH). Ciprofol, a novel intravenous sedative agent analogous to propofol, has not yet been proven efficacious in alleviating RIH. The present study aimed to investigate the effect of ciprofol on RIH and the possible mechanisms involved. METHODS: The RIH model was established by an infusion of remifentanil (1 µg·kg-1·min-1) 60 min in rats with incisional pain. Ciprofol (0.1, 0.25, and 0.4 mg·kg-1·min-1) was simultaneously infused to evaluate its effect on RIH. The antinociception of ciprofol was verified by measured paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL). γ-aminobutyric acid type A receptor α2 subunit (α2GABAAR), N-methyl-d-aspartate receptor NR2B subunit (NR2B), calcium/calmodulin-dependent protein kinase II α (CaMKIIα), and phosphorylated CaMKIIα (P-CaMKIIα) in the spinal cord and hippocampus of rats were assessed by western blotting and immunohistochemistry. KEY FINDINGS: The results showed that ciprofol dose-dependently increased PWMT and PWTL values in RIH rats. Moreover, ciprofol upregulated α2GABAAR and downregulated NR2B and P-CaMKIIα in the rat spinal cord and hippocampus. CONCLUSIONS: Ciprofol alleviates RIH effectively, and the anti-hyperalgesic mechanisms may involve increasing α2GABAAR levels and decreasing NR2B and P-CaMKIIα levels in the spinal cord and hippocampus.

Efficacy and safety of ciprofol versus propofol for anesthesia induction in adult patients received elective surgeries: a meta­analysis.

BACKGROUND: Propofol is use widely used in anesthesia, known for its effectiveness, may lead to cardiopulmonary issues in some patients. Ciprofol has emerged as a possible alternative to propofol because it can achieve comparable effects to propofol while causing fewer adverse events at lower doses. However, no definitive conclusion has been reached yet. This meta-analysis aimed to evaluate the efficacy and safety of ciprofol versus propofol in adult patients undergoing elective surgeries under general anesthesia. METHODS: We searched PubMed, EMBASE, the Cochrane library, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) to identify potentially eligible randomized controlled trials (RCT) comparing ciprofol with propofol in general anesthesia until September 30, 2023. The efficacy outcomes encompassed induction success rate, time to onset of successful induction, time to disappearance of eyelash reflex, and overall estimate means in Bispectral Index (BIS). Safety outcomes were assessed through time to full alertness, incidence of hypotension, incidence of arrhythmia, and incidence of injection-site pain. Continuous variables were expressed as mean difference (MD) with 95% confidence interval (CI), and dichotomous variables were expressed as risk ratio (RR) with 95% CI. Statistical analyses were performed using RevMan 5.4 and STATA 14.0. The quality of the evidence was rated through the grading of recommendations, assessment, development and evaluation (GRADE) system. RESULTS: A total of 712 patients from 6 RCTs were analyzed. Meta-analysis suggested that ciprofol was equivalent to propofol in terms of successful induction rate, time to onset of successful induction, time to disappearance of eyelash reflex, time to full alertness, and incidence of arrhythmia, while ciprofol was better than propofol in overall estimated mean in BIS (MD: -3.79, 95% CI: -4.57 to -3.01, p < 0.001), incidence of hypotension (RR: 0.63, 95% CI: 0.42 to 0.94, p = 0.02), and incidence of injection-site pain (RR: 0.26, 95% CI: 0.14 to 0.47, p < 0.001). All results were supported by moderate to high evidence. CONCLUSIONS: Ciprofol may be a promising alternative to propofol because it facilitates achieving a satisfactory anesthesia depth and results in fewer hypotension and injection-site pain. However, we still recommend conducting more studies with large-scale studies to validate our findings because only limited data were accumulated in this study. TRIAL REGISTRATION: PROSPERO 2023 CRD42023479767.

The Effect of Ciprofol on Postoperative Delirium in Elderly Patients Undergoing Thoracoscopic Surgery for Lung Cancer: A Prospective, Randomized, Controlled Trial.

Purpose: This study was conducted to assess whether ciprofol vs propofol could affect the incidence of postoperative delirium (POD) in elderly patients with lung cancer after thoracoscopic surgery. Patients and Methods: In this study, a total of 84 elderly patients undergoing thoracoscopic surgery for lung cancer were recruited and randomized into two groups to receive anesthesia with either ciprofol or propofol. The primary outcome was the incidence of POD within three days after surgery. Secondary outcomes included the Confusion Assessment Method (CAM) score, intraoperative indicators related to mean arterial pressure (MAP), and cerebral tissue oxygen saturation (SctO2). Moreover, MAP- and SctO2-related indicators associated with POD were analyzed. Results: The incidence of POD was 7.1% and 16.7%, respectively, in the ciprofol group and the propofol group (risk ratio [RR], 0.37; 95% confidence interval [CI], 0.07 to 2.03; risk difference [RD], -9.6%; 95% CI, -23.3% to 4.1%; p = 0.178). Compared with those in the propofol group, patients in the ciprofol group had lower CAM scores three days after surgery (13 (12, 15) vs 15 (14, 17); 12 (11, 13) vs 14 (13, 16); 12 (11, 12) vs 13 (12, 14), p<0.05). Besides, patients in the ciprofol group exhibited higher mean and minimum MAP (88.63 ± 6.7 vs 85 ± 8.3; 69.81 ± 9.59 vs 64.9 ± 9.43, p<0.05) and SctO2 (77.26 ± 3.96 vs 75.3 ± 4.49, 71.69 ± 4.51 vs 68.77 ± 6.46, p<0.05) and percentage of time for blood pressure stabilization (0.6 ± 0.14 vs 0.45 ± 0.14, p<0.05) than those in the propofol group. Furthermore, MAP and SctO2-related indicators were validated to correlate with POD. Conclusion: Anesthesia with ciprofol did not increase the incidence of POD compared with propofol. The results demonstrated that ciprofol could improve intraoperative MAP and SctO2 levels and diminish postoperative CAM scores.

Efficacy and safety of Ciprofol compared with Propofol during general anesthesia induction: A systematic review and meta-analysis of randomized controlled trials (RCT).

BACKGROUND: Ciprofol, a newer entrant with similarities to propofol, has shown promise with a potentially improved safety profile, making it an attractive alternative for induction of general anesthesia. This meta-analysis aimed to assess the safety and efficacy of ciprofol compared with propofol during general anesthesia induction. METHODS: A comprehensive literature search was conducted using PubMed, Clinical Trial.gov, and Cochrane Library databases from inception to July 2023 to identify relevant studies. All statistical analyses were conducted using R statistical software version 4.1.2. RESULTS: Thirteen Randomized Controlled Trials (RCTs) encompassing a total of 1998 participants, were included in our analysis. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for postoperative hypertension, bradycardia, or tachycardia. CONCLUSION: In conclusion, Ciprofol is not inferior to Propofol in terms of its effectiveness in general anesthesia. Ciprofol emerges as a valuable alternative sedative with fewer side effects, especially reduced injection pain, when compared to Propofol. SUMMARY: Propofol, frequently utilized as an anesthetic, provides swift onset and quick recovery. However, it has drawbacks such as a narrow effective dosage range and a high occurrence of adverse effects, particularly pain upon injection. Ciprofol, a more recent drug with propofol-like properties, has demonstrated promise and may have an improved safety profile, making it a compelling alternative for inducing general anesthesia. This meta-analysis compared the safety and effectiveness of Ciprofol with Propofol for general anesthesia induction in a range of medical procedures, encompassing thirteen Randomized Controlled Trials (RCTs) and 1998 individuals. The pooled analysis indicated that Ciprofol was associated with a notably lower incidence of pain upon injection [RR: 0.15; 95% CI: 0.10 to 0.23; I^2 = 43%, p < 0.0000001] and was non-inferior to propofol in terms of anesthesia success rate [RR: 1.00; 95% CI: 0.99 to 1.01; I^2 = 0%; p = 0.43]. In terms of safety, the incidence of hypotension was significantly lower in the ciprofol group [RR:0.82; 95% CI:0.68 to 0.98; I^2 = 48%; p = 0.03]. However, no statistically significant differences were found for hypertension, bradycardia, or tachycardia. In conclusion, ciprofol is equally effective at inducing and maintaining general anesthesia as propofol. When compared to propofol, ciprofol is a better alternative sedative for operations including fiberoptic bronchoscopy, gynecological procedures, gastrointestinal endoscopic procedures, and elective surgeries because it has less adverse effects, most notably less painful injections.

Effective doses of ciprofol combined with alfentanil in inhibiting responses to gastroscope insertion, a prospective, single-arm, single-center study.

BACKGROUND: Ciprofol is a novel intravenous sedative and anesthetic. Studies have shown that it features a rapid onset of action, a fast recovery time, slight inhibition of respiratory and cardiovascular functions, and a low incidence of adverse reactions. This study aims to explore the median effective dose (ED50) and the 95% effective dose (ED95) of ciprofol in inhibiting responses to gastroscope insertion when combined with a low dose of alfentanil, and to evaluate its safety, to provide a reference for the rational use of ciprofol in clinical practices. METHODS: We included 25 patients aged 18-64 years of either sex who underwent gastroscopy under intravenous general anesthesia, with a Body Mass Index (BMI) 18-28 kg/m2, and an American Society of Anesthesiologists (ASA) grade I or II. In this study, the dose-finding strategy of ciprofol followed a modified Dixon's up-and-down method with an initial dose of 0.30 mg/kg and an increment of 0.02 mg/kg. Ciprofol was administered after intravenous injection of 7 µg/kg of alfentanil, and 2 min later a gastroscope was inserted. When the insertion response of one participant was positive (including body movement, coughing, and eye opening), an escalation of 0.02 mg/kg would be given to the next participant; otherwise, a de-escalation of 0.02 mg/kg would be administered. The study was terminated when negative response and positive response alternated 8 times. A Probit model was used to calculate the ED50 and ED95 of ciprofol in inhibiting responses to gastroscope insertion when combined with alfentanil. Patients' recovery time, discharge time, vital signs and occurrence of adverse reactions were recorded. RESULTS: The ED50 of single-dose intravenous ciprofol injection with 7 µg/kg of alfentanil in inhibiting gastroscope insertion responses was 0.217 mg/kg, and the ED95 was 0.247 mg/kg. Patients' recovery time and discharge time were 11.04 ± 1.49 min and 9.64 ± 2.38 min, respectively. The overall incidence of adverse reactions was 12%. CONCLUSION: The ED50 of ciprofol combined with 7 µg/kg of alfentanil in inhibiting gastroscope insertion responses was 0.217 mg/kg, and the ED95 was 0.247 mg/kg. Ciprofol showed a low incidence of anesthesia-related adverse events. TRIAL REGISTRATION: http://www.chictr.org.cn (ChiCTR2200061727).

Dreaming during gastrointestinal endoscopy under propofol, ciprofol, or remimazolam anesthesia: study protocol for a parallel-design double-blind, single-center trial.

BACKGROUND: Dreaming sometimes occurs during sedation. It has been reported that factors such as different anesthetics, depth of anesthesia, age, sex, and preoperative psychological state may affect dreams. Ciprofol and remimazolam are novel choices for painless endoscopy. Herein, we aimed to investigate dreaming during gastrointestinal endoscopy under propofol, ciprofol, and remimazolam anesthesia respectively. METHODS: This is a prospective, parallel-design double-blind, single-center clinical trial. Three hundred and sixty subjects undergoing elective painless gastroscopy, colonoscopy, or gastroenteroscopy will be enrolled. Eligible subjects will undergo propofol-, ciprofol-, or remimazolam-induced anesthesia to finish the examination. Interviews about the modified Brice questionnaire will be conducted in the recovery room. Incidence of dreaming is set as the primary outcome. Secondary outcomes include type of dreams, improvement of sleep quality, evaluation of patients, incidence of insufficient anesthesia, and intraoperative awareness. Safety outcomes are the incidences of hypotension and hypoxia during examination and adverse events during recovery. DISCUSSION: This study may observe different incidences of dreaming and diverse types of dreams, which might lead to different evaluations to the anesthesia procedure. Based on the coming results, anesthesiologists can make a better medication plan for patients who are going to undergo painless diagnosis and treatment. TRIAL REGISTRATION: This trial was registered at the Chinese Clinical Trial Registry on May 18, 2023 (registration number ChiCTR2300071565).

Ciprofol is primarily glucuronidated by UGT1A9 and predicted not to cause drug-drug interactions with typical substrates of CYP1A2, CYP2B6, and CYP2C19.

Ciprofol is a novel intravenous anesthetic agent. Its major glucuronide metabolite, M4, is found in plasma and urine. However, the specific isoforms of UDP-glucuronosyltransferases (UGTs) that metabolize ciprofol to M4 remain unknown. This study systematically characterized UGTs that contribute to the formation of M4 using human liver microsomes (HLM), human intestinal microsomes (HIM), and human recombinant UGTs. The inhibitory potential of ciprofol and M4 against major human UGTs and cytochrome P450 enzymes (P450s) was also explored. In vitro-in vivo extrapolation (IVIVE) and physiologically-based pharmacokinetic (PBPK) simulations were performed to predict potential in vivo drug-drug interactions (DDIs) caused by ciprofol. Glucuronidation of ciprofol followed Michaelis-Menten kinetics in both HLM and HIM with apparent Km values of 345 and 412 µM, Vmax values of 2214 and 444 nmol min-1·mg protein-1, respectively. The in vitro intrinsic clearances (CLint = Vmax/Km) for ciprofol glucuronidation by HLM and HIM were 6.4 and 1.1 µL min-1·mg protein-1, respectively. Human recombinant UGT studies revealed that UGT1A9 is the predominant isoform mediating M4 formation, followed by UGT1A7, with UGT1A8 playing a minor role. Ciprofol competitively inhibited CYP1A2 (Ki = 12 µM) and CYP2B6 (Ki = 4.7 µM), and noncompetitively inhibited CYP2C19 (Ki = 29 µM). No time-dependent inhibition by ciprofol was noted for CYP1A2, CYP2B6, or CYP2C19. In contrast, M4 showed limited or no inhibitory effects against selected P450s. Neither ciprofol nor M4 inhibited UGTs significantly. Initial IVIVE suggested potential ciprofol-mediated inhibition of CYP1A2, CYP2B6, and CYP2C19 inhibition in vivo. However, PBPK simulations showed no significant effect on phenacetin, bupropion, and S-mephenytoin exposure or peak plasma concentration. Our findings are pertinent for future DDI studies of ciprofol as either a perpetrator or victim drug.