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.

Remimazolam vs Etomidate: Haemodynamic Effects in Hypertensive Elderly Patients Undergoing Non-Cardiac Surgery.

Background: Remimazolam tosilate (RT) is a novel ultrashort-acting γ-aminobutyric acid subtype A (GABAA) agonist, with several advantages including rapid induction and recovery, stable haemodynamics, and mild respiratory inhibition. However, studies have not been conducted to explore the haemodynamic effects of RT in elderly hypertensive subjects undergoing non-cardiac surgery. Therefore, we sought to compare the effects of anaesthesia induction using different doses of RT and etomidate on the haemodynamics of this group of patients. Methods: Patients were recruited into this single-center, prospective, randomized, double-blind trial from October 2022 to June 2023. A total of 150 hypertensive elderly undergoing non-cardiac surgery were randomly assigned into 0.2 mg/kg RT group (Group RL), 0.3 mg/kg RT group (Group RH) and 0.3 mg/kg etomidate group (Group E). The primary outcome of the study was haemodynamic changes (mean arterial pressure fluctuation value -∆MAP and heart rate fluctuation value -∆HR) observed during anaesthesia induction. Secondary outcomes included incidence of adverse cardiovascular events and adverse drug reactions (injection pain and myoclonus), cumulative doses of vasoactive drugs and vital signs at different time points. Results: Patients in Group E and Group RL had significantly lower haemodynamic fluctuations (∆MAP), lower incidence of hypotension and cumulative dose of ephedrine than subjects in Group RH. Patients in groups RL and RH had significantly lower incidence of injection pain and myoclonus compared with patients in group E. The results showed no statistically significant differences in ∆HR, hypertension, bradycardia, tachycardia, and time to loss of eye-opening reflex and start of intubation, and vital signs at different time points among the three groups. Conclusion: Use of low-dose RT (0.2 mg/kg) for induction of non-cardiac surgical anaesthesia in elderly hypertensive patients is more effective in maintaining haemodynamic stability and has fewer adverse effects compared with etomidate.

Comparison of Remimazolam Tosilate and Etomidate on Hemodynamics in Cardiac Surgery: A Randomised Controlled Trial.

Background: Remimazolam tosilate (RT) is a new ultrashort-acting γ-aminobutyric acid subtype A (GABAA) agonist, with the characteristics of rapid onset and offset, minimal cardiorespiratory depression. Currently, few studies have compared the effect of RT and etomidate on hemodynamics during anesthesia induction. Here, we aimed to compare the hemodynamic effects of different doses of RT and etomidate for anesthesia induction in patients undergoing cardiac surgeries. Methods: Patients were recruited from January to September 2022 in this single-center, prospective, randomized, double-blind trial. A total of 117 patients undergoing selective valve replacement surgery were randomly divided into low-dose RT (0.2 mg/kg) group (group LR), high-dose RT (0.3 mg/kg) group (group HR), or etomidate (1.5 mg/kg) group (group E), respectively. The primary outcome was hemodynamic fluctuations (mean arterial pressure fluctuation value [∆MAP]; heart rate fluctuation value [∆HR]) during anesthesia induction. Secondary outcomes included the incidence of adverse drug reactions (injection pain and myoclonus) and adverse cardiovascular events, vital signs at different time points and the cumulative doses of vasoactive drugs. Results: The hemodynamic fluctuations (∆MAP) in group LR and group E were significantly lower than that in group HR. In addition, the incidence of hypotension and the cumulative norepinephrine doses in group E and group LR were also significantly lower than that in group HR. Furthermore, the incidence of injection pain and myoclonus in group LR and group HR were less frequently recorded compared with group E. There were no significant differences in terms of ∆HR, tachycardia, hypertension, severe bradycardia, vital signs at different time points, lactic acid and blood glucose between both groups. Conclusion: Compared with etomidate, low-dose RT (0.2mg/kg) can not only provide stable hemodynamic parameters but also cause fewer adverse reactions when used for anesthesia induction in patients with cardiac disease.

Effect of remimazolam tosilate versus etomidate on hemodynamics in patients undergoing valve replacement surgery: study protocol for a randomized controlled trial.

BACKGROUND: Patients with a history of cardiac disease are prone to develop cardiovascular adverse events such as hypotension, hypertension, and tachycardia during anesthesia induction. Therefore, hemodynamic stability is one of the most important concerns for induction of anesthesia in patients undergoing cardiac surgery. Remimazolam tosilate is a new, ultra-short-acting benzodiazepine agent, with the advantages of rapid onset, rapid offset, and minimal cardiorespiratory depression. We aim to compare the effect of remimazolam tosilate and etomidate on hemodynamics during anesthesia induction in patients undergoing valve replacement surgery. METHODS/DESIGN: The trial is a prospective, randomized, double-blinded, controlled, single-center trial to compare the effect of remimazolam tosilate and etomidate on hemodynamics in patients undergoing valve replacement surgery. One hundred seventeen patients undergoing selective valve replacement surgery between January 1, 2022, and December 31, 2023, will be enrolled and randomly allocated into one of three groups: low-dose remimazolam group (Group LR), high-dose remimazolam group (Group HR), or etomidate group (Group E). The primary outcome is hemodynamic fluctuations during anesthesia induction (the difference between mean arterial pressure [MAP] to baseline, ▴MAP; and the difference between maximum or minimum heart rate [HR] and baseline, ▴HR). Secondary outcomes include the incidence of adverse cardiovascular events (hypotension, severe bradycardia, hypertension, tachycardia, and arrhythmia), the cumulative doses of vasoactive drugs used per patient, incidence and degree of injection pain and myoclonus, blood glucose values, and vital signs at different time points. DISCUSSION: This research will determine the effectiveness and safety of remimazolam tosilate induction on hemodynamics in patients undergoing valve replacement surgery. TRIAL REGISTRATION: www.chictr.org .cn identifier ChiCTR2100052535 . Registered on 17th Dec 2021, http://www.chictr.org.cn/ ).

Effect of Remimazolam Tosilate on Respiratory Depression in Elderly Patients Undergoing Gastroscopy: A Multicentered, Prospective, and Randomized Study.

Background: Remimazolam tosilate (RT) is a new type of γ-aminobutyric acid subtype A (GABAA) receptor agonist, having the possibility to be an ideal sedative drug for procedural sedation. At present, there are few studies on the effect of RT on respiratory depression in elderly patients. We aimed to evaluate the effect of RT on respiratory depression in elderly patients undergoing gastroscopy. Methods: This prospective, randomized, single-blinded trial recruited patients from eight centers in China between May 2022 and July 2022. A total of 346 elderly patients undergoing gastroscopy were randomly divided into RT group (0.2 mg/kg) or propofol group (1.5 mg/kg), respectively. The primary outcome was the incidence of respiratory depression. Secondary outcomes include the incidence of sedative-related adverse events, the success rate of sedation, time to fully alert, time to loss of consciousness (LOC), time to ready for discharge, as well as the the patients, endoscopists and anethetists' satisfaction. Results: The incidence of respiratory depression was significantly reduced in the RT group compared with the propofol group (9.8% vs 17.9%, P=0.042). The time of LOC and fully alert in the RT group were longer than that in the propofol group (P < 0.05). The incidences of hypotention (50.9% vs 32.4%, P=0.001) and hypotension requiring treatment (5.8% vs 1.7%, P=0.031) were significantly higher in the propofol group than that in the RT group. The incidence and severity of injection pain were more frequently recorded in the propofol group than that in the RT group (40.5% vs 12.1%, P<0.05). There were no statistically significant differences between the two groups in terms of sedation success rates, time to ready for discharge, endoscopists and anethetists' satisfaction and other sedative-related adverse events. Conclusion: RT may be a suitable alternative sedative agent for elderly patients undergoing gastroscopy due to its safety profile.

Effect of different doses of esketamine compared with fentanyl combined with propofol on hypotension in patients undergoing painless abortion surgery: a prospective, randomized, double-blind controlled clinical trial.

BACKGROUND: Opioids analgesics commonly used in abortion procedures are associated with respiratory and circulatory depression. Esketamine is a N-methyl-D-aspartate receptor (NMDA) antagonist and a common analgesic. The drug has several advantages including rapid onset and offset and it causes minimal cardiorespiratory depression. However, studies have not explored the effects of esketamine in patients undergoing painless abortion surgery. Therefore, the present study sought to evaluate the effect of different doses of esketamine compared with the effect of fentanyl on incidence of perioperative hypotension in patients undergoing painless abortion surgery and to explore the optimal esketamine dose for this population. METHODS: A total of 178 female patients undergoing painless abortion surgery were enrolled to the current study. The patients were aged 18-45 years, had a body mass index (BMI) of 18-28 kg m- 2 and a class I or II physical status as determined using the American Society of Anesthesiologists (ASA) system. Patients were randomly assigned to four groups as follows: group F (n = 45) in which patients underwent intravenous (IV) administration of 1 µg kg- 1 fentanyl followed by IV administration of 2 mg kg- 1 propofol, and group EL, group EM and group EH (n = 45, 44, 44) with patients receiving IV administration of 0.2 mg kg- 1, 0.25 mg kg- 1, 0.3 mg kg- 1 esketamine, respectively, followed by IV administration of 2 mg kg- 1 propofol. The primary outcome of the study was the incidence of hypotension whereas secondary outcomes included incidence of adverse events, perioperative changes of vital signs, anesthesia induction time, recovery time and dischargeable time, propofol addition, as well as patient, surgeon and anesthesiologist satisfaction levels. RESULTS: The findings showed that the incidence of hypotension was significantly lower in subjects in group EL, group EM and group EH (0, 0, 0%) relative to the incidence in patients in group F (20%) (χ2 = 19.648; P = 0.000). In this study, the incidence of hypoxia of subjects in group EL, group EM and group EH (0, 2.3, 2.3%) was significantly lower compared with that of patients in group F (11.1%) (χ2 = 8.622; P = 0.035). The findings indicated that the incidence of somatic motor reactions was significantly lower in participants in group EM and group EH (9.1, 4.5%) relative to that of patients in group F and group EL (26.7, 15.6%) (χ2 = 10.254; P = 0.016). The results showed that the incidence of nausea and vomiting and potential psychiatric symptoms were significantly higher in patients in group EH (15.9, 11.4%) compared with that of participants in group F (2.2, 0%), group EL (4.4, 0%) and group EM (2.3, 2.3%) (χ2 = 7.493; P = 0.038 and χ2 = 8.248; P = 0.003). In this study, the mean arterial pressure (MAP) and heart rate (HR) of subjects in group EL, group EM and group EH were more stable compared with that of patients in group F. Frequency of the additional propofol dose was markedly less in group EM and EH (26.7%, 17,8%) compared with that in group F and EL (9.1, 4.5%) (χ2 = 10.254; P = 0.016). The findings indicated that the dischargeable time was significantly shorter for patients in group EM compared with that of subjects in group F, group EL and group EH. CONCLUSIONS: The findings of the present study showed that single-dose esketamine (0.25 mg kg- 1) effectively decreased incidence of hypotension and total adverse events and reduced the frequency of additional propofol dose required for patients undergoing painless abortion with preservation of physician-patient satisfaction.

T1AM Attenuates the Hypoxia/Reoxygenation-Induced Necroptosis of H9C2 Cardiomyocytes via RIPK1/RIPK3 Pathway.

Purpose: To investigate the detailed mechanism of 3-iodothyronamine (T1AM) in cell apoptosis and programmed necrosis of hypoxia/reoxygenation- (H/R-) induced H9C2 injury. Materials and Methods: Cardiomyocyte H9C2 cells were cultured in vitro for the establishment of cardiomyocyte H/R models. Cells were randomly divided into four groups: the control group, H/R group, T1AM pretreatment group, T1AM pretreatment and H/R (6 µm T1AM+H/R) group. The degree of myocardial injury was determined by the detection of the cardiomyocyte inhibition rate by CCK8 and the detection of lactic dehydrogenase (LDH) activity. Cell apoptosis was assessed through TUNEL assay and flow cytometry analysis. The protein level and mRNA level of RIPK1, RIPK3, and CAMKII were detected by western blotting and qRT-PCR. Results: Compared with the control group, the cell inhibition rate was dramatically elevated in the H/R group. LDH release of cardiomyocytes was significantly increased. Protein and mRNA expressions of RIPK1, RIPK3, and CAMKII were significantly enhanced. Compared with the H/R group, the cell inhibition rate, LDH release, cardiomyocyte necroptosis rate, and protein and mRNA levels of RIPK1, RIPK3, and CAMKII of the T1AM+H/R group were significantly decreased. Conclusion: Pretreatment with T1AM could alleviate cardiomyocytes' H/R injury and inhibit necroptosis of cardiomyocytes, which might exert a protective function upon activation of the RIPK1/RIPK3 pathway.

3-iodothyronamine inhibits apoptosis induced by myocardial ischemia reperfusion via the Akt/FoxO1 signaling pathway.

Background: This study investigated the potential effects of 3-iodothyronamine (T1AM) on myocardial ischemia reperfusion injury (MIRI) and the underlying molecular mechanisms. Methods: A total of 16 adult male Sprague-Dawley rats were randomly divided into 4 groups and administered the following: control [60% dimethyl sulfoxide (DMSO) and 40% saline, pH 7.4], T1AM (25 mg/kg), T1AM (50 mg/kg), or T1AM (100 mg/kg). The rectal temperatures of the rats were measured at different time points. A further 30 adult male Sprague-Dawley rats were randomized and divided into the following 3 groups (n=10 in each group): sham operation, ischemia/reperfusion (I/R), and I/R + T1AM. In the I/R and I/R + T1AM groups, the left anterior descending (LAD) coronary artery of the rats were occluded for 0.5 hour to induce myocardial ischemia, followed by reperfusion for 3 hours in the I/R group. The electrocardiography (ECG), cardiac function, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were examined in rats to evaluate the myocardial injury. The differences in the expression of apoptosis-related and Akt-FoxO1 signaling-related proteins were determined via Western blot. Results: This work verified that T1AM reduced the body temperature of rats in a dose-dependent manner. Additionally, T1AM improved cardiac function and decreased the infarction size caused by MIRI. T1AM reduced the expression of biochemical parameters and apoptosis of myocardial cells. In addition, after treatment with T1AM, the expression of Glut1, pFoxO1 and Akt were reduced, while the expression of FoxO1 and PPARα were increased significantly. Conclusions: Pretreatment of cardiomyocytes with T1AM inhibited apoptosis and protected against ischemia reperfusion injury via the Akt/FoxO1 signaling pathway.

Higher versus lower mean arterial pressure target management in older patients having non-cardiothoracic surgery: A prospective randomized controlled trial.

STUDY OBJECTIVE: This study aimed to evaluate the effects of low versus high mean arterial pressure (MAP) levels on the incidence of postoperative delirium during non-cardiothoracic surgery in older patients. DESIGN: Multicenter, randomized, parallel-controlled, open-label, and assessor-blinded clinical trial. SETTING: University hospital. PATIENTS: Three hundred twenty-two patients aged ≥65 with an American Society of Anesthesiologists physical status of I-II who underwent non-cardiothoracic surgery with general anaesthesia. INTERVENTIONS: Participants were randomly assigned into a low-level MAP (60-70 mmHg) or high-level MAP (90-100 mmHg) group during general anaesthesia. The study was conducted from November 2016 to February 2020. Participants were older patients having non-cardiothoracic surgery. The follow-up period ranged from 1 to 7 days after surgery. The primary outcome was the incidence of postoperative delirium. MAIN RESULTS: In total, 322 patients were included and randomized; 298 completed in-hospital delirium assessments [median (interquartile range) age, 73 (68-77) years; 173 (58.1%) women]. Fifty-four (18.1%) patients total, including 36 (24.5%) and 18 (11.9%) in the low-level and high-level MAP groups [relative risk (RR) 0.48, 95% confidence interval (CI) 0.25 to 0.87, P = 0.02], respectively, experienced postoperative delirium. The adjusted RR was 0.34 (95% CI 0.16 to 0.70, P < 0.01) in the multiple regression analysis. High-level MAP was associated with a shorter delirium span and a higher intraoperative urine volume than low-level MAP. CONCLUSIONS: In older patients during non-cardiothoracic surgery, high-level blood pressure management might help reduce the incidence of postoperative delirium.

Dexmedetomidine inhibits pyroptosis by down-regulating miR-29b in myocardial ischemia reperfusion injury in rats.

OBJECTIVE: Dexmedetomidine (DEX) was reported to protect heart against ischemic-reperfusion (IR) but the mechanism herein remains elusive. This study aims to explore the mechanism of DEX on pyroptosis induced by myocardial ischemic reperfusion (MIR). METHODS: MIR rat models were established and injected DEX or miR-29b agomir/antagomir separately. The possible effect of DEX or miR-29b on myocardial cells was assessed according to measurement on creatine kinase-MB (CK-MB), cardiac troponin I (cTnI), interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), myocardial infarction size, myocardial injury and apoptosis. Western blot determined the expression levels of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and cleaved-caspase-1. Hypoxia/reoxygenation (H/R) cell model was established. The lactate dehydrogenase (LDH) content released by myocardial cells was examined. The relation between miR-29b and FoxO3a was confirmed by dual luciferase reporter gene assay. FoxO3a or ARC level was elevated in H/R myocardial cells to detect its effect on pyroptosis. RESULTS: MIR rat models were successfully established, in which cell pyroptosis was triggered as evidenced by increased expression levels of NLRP3, ASC and cleaved-caspase-1. Rats with DEX precondition had attenuated cell pyroptosis and ameliorated inflammatory response. FoxO3a was a target of miR-29b. MiR-29b agomir or miR-29b antagomir could inhibit or promote the protective effect of DEX on MIR. Overexpression of FoxO3a/ARC axis could suppress myocardial pyroptosis induced by H/R. CONCLUSION: DEX could ameliorate MIR injury (MIRI) and H/R injury in rats and inhibit H/R induced pyroptosis in myocardial cells via down-regulating miR-29b to activate FoxO3a/ARC axis.

A Comparison of Dexmedetomidine and Midazolam for the Prevention of Postoperative Nausea and Vomiting Caused by Hemabate in Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To compare the efficacy of dexmedetomidine and midazolam in the prevention of postoperative nausea and vomiting (PONV) caused by hemabate in postpartum hemorrhage during cesarean delivery. METHODS: One hundred and five parturients with American Society of Anesthesiology (ASA) physical status I and II, aged 20-40 years, undergoing elective cesarean delivery under epidural anesthesia were randomly allocated into dexmedetomidine group (group D, n=35), midazolam group (group M, n=35) and control group (group C, n=35). Patients received an intrauterine injection of 250 µg hemabate and continuous intravenous infusion of 5 units oxytocin immediately following the delivery of the infant. At the same time, patients in group D received 1µg/kg intravenous dexmedetomidine, group M received 0.02 mg/kg intravenous midazolam and group C received 20 mL intravenous saline. Parameters such as the PONV, other adverse reactions (chest distress, flush, etc.) caused by hemabate, patient satisfaction, the sedation (OAA/S) scores, and the hemodynamic parameters were recorded in both groups. RESULTS: The PONV incidence in group D and group M was significantly lower compared with group C (6%, 17%, and 71% for group D, group M, and group C, respectively, P<0.05). The sedation (OAA/S) scores in group D and group M was significantly higher compared with group C (1.62±0.28, 1.75±0.31, and 1.00±0.00 for group D, group M, and group C, respectively, P<0.05). The patient satisfaction in group D and group M was significantly higher compared with group C (94%, 69%, and 46% for group D, group M, and group C, respectively, P<0.05). Furthermore, there were more patients satisfied with group D than group M (94% vs.69%, P<0.05). CONCLUSION: Intravenous dexmedetomidine (1 µg/kg) and midazolam (0.02 mg/kg) were equally effective in preventing PONV introduced by hemabate and dexmedetomidine is superior to midazolam in patient satisfaction.