Background: Rapid reversal of neuromuscular block after surgery and anesthesia is often necessary. Here, we reported the primary efficacy and safety data from a phase IIa study on adamgammadex sodium, a newly developed modified γ-cyclodextrin derivative.Methods: This was a phase IIa, single-center, randomized, open-label, and dose-finding study that enrolled 35 patients under general anesthesia who received the neuromuscular blocking agent rocuronium for induction and maintenance of neuromuscular blockade. The subjects were randomized to one of the five adamgammadex dose groups (2, 4, 6, 8, and 10 mg kg−1) and to the 4 mg kg−1 sugammadex group. Pharmacological efficacy was the recovery time from the start of adamgammadex or sugammadex administration to train-of-four (TOF) ratio ≥0.9, 0.8, and 0.7 among the different dose groups. Adverse events were recorded throughout the study.Results: The efficacy in reversing deep neuromuscular block was the same between 4 mg kg−1 sugammadex and adamgammadex. However, in the lowest dose groups of 2 and 4 mg kg−1 adamgammadex, adequate reversal could not be achieved in all subjects. The recovery time of TOF ratio to 0.9, 0.8, and 0.7 was shorter in the adamgammadex 10 mg kg−1 group than in the sugammadex 4 mg kg−1 group. The average values of the TOF ratio after 3 min of administration of adamgammadex 8 and 10 mg kg−1 and sugammadex 4 mg kg−1 were >90%. There were no serious adverse events after the use of adamgammadex, and no subjects had to be withdrawn from the trial.Conclusions: Adamgammadex enabled quick, predictable, and tolerable reversion of rocuronium-induced deep neuromuscular block in a dose-dependent manner. Adamgammadex doses of 6–10 mg kg−1 might be the recommended dose range for further exploration of efficacy. Clinical Trial Registration: This study was registered at chictr.org.cn, identifier: ChiCTR2000038391.

Introduction: This study investigated whether transcutaneous electrical acupuncture point stimulation (TEAS) at PC6 can reduce the proportion of elderly patients experiencing a drop of ⩾4% in peripheral capillary oxygen saturation (SpO2) while undergoing colonoscopy under sedation. Methods: A total of 32 elderly patients (aged ⩾ 65 years) scheduled for colonoscopy were randomly assigned in a 1:1 ratio to receive either real or sham TEAS (treatment or control groups, respectively). Each patient received oxygen (2 L/min) delivered routinely via nasal cannula. The treatment group was given TEAS at PC6 for 20 min at 2 Hz frequency and 6 mA intensity; the control group underwent the same procedures but with zero frequency/intensity. SpO2 and other physiological parameters were measured prior to sedation and colonoscopy (baseline) and at seven other timepoints through departure from recovery. Depth of anesthesia was measured using a Narcotrend monitor. Results: Significantly fewer patients in the treatment group experienced a ⩾4% decrease from baseline SpO2 (2/16) than patients in the control group (10/16; p = 0.004). The two groups were comparable with regard to respiratory rate, systolic and diastolic blood pressures, mean arterial pressure, and heart rate. Conclusion: TEAS applied at PC6 with 2 Hz frequency was feasible and may be helpful in reducing the rate of hypoxia in elderly patients during colonoscopy. Trial registration number: NCT03775122 (ClinicalTrials.gov).

Background: Although major joint replacement surgery has a high overall success rate, postoperative cognitive dysfunction (POCD) is a common complication after anesthesia and surgery, increasing morbidity and mortality. Identifying POCD risk factors would be helpful to prevent and decrease the occurrence of POCD. We hypothesized that preoperative chronic pain increases the risk of POCD.Methods: A single-center, observational, prospective cohort study was conducted from January 2018 to March 2020. All consecutive elderly patients (>65 years) who underwent elective total hip arthroplasty or hemiarthroplasty with general anesthesia by the same surgeon were enrolled. The patients underwent neuropsychological testing preoperatively and at 7 days and 2 months after surgery. To determine POCD, a nonsurgical control group was recruited from the general community.Results: Of the 141 patients who finished the neuropsychological testing 7 days after surgery, 61 (43.2%) had preoperative chronic pain. Of the 61 patients, 17 (27.9%) developed POCD; of the 79 patients with no chronic pain, 10 (12.7%) had developed POCD by 7 days after surgery. Multivariate logistic regression analysis identified preoperative chronic pain as a risk factor of POCD assessed 7 days after surgery (odds ratio 6.527; P = 0.009). There was no significant difference in the POCD incidence 2 months after surgery between patients with and without preoperative chronic pain.Conclusion: Preoperative chronic pain was a risk factor of developing POCD within 7 days after surgery in elderly patients following hip joint replacement surgery.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03393676].

Background Gastrointestinal endoscopy has been associated with difficult experiences and can leave patients with an unpleasant impression. Propofol and midazolam are the most commonly used intravenous anesthetics for sedation during gastrointestinal endoscopy. However, cardiac and pulmonary adverse events are the primary concerns associated with the use of these sedatives. Remimazolam tosylate is an ultra-short-acting benzodiazepine drug with a mild inhibitory effect on the respiratory and circulatory systems. These properties qualify remimazolam tosylate to be used as a replacement for propofol or midazolam as a sedative during gastrointestinal endoscopy. This study aims to describe the efficacy and safety of remimazolam tosylate as a sedative for upper gastrointestinal endoscopy. Methods A multicenter, randomized, single-blind, parallel-controlled, noninferiority clinical study will be conducted to evaluate the efficacy and safety of remimazolam tosylate as a sedative during upper gastrointestinal endoscopy. Participants (n = 1800) will be randomized to receive remimazolam tosylate at 0.15 mg/kg (experimental group 1), remimazolam tosylate at 0.2 mg/kg (experimental group 2), or propofol at 1.5 mg/kg (control group). Procedure success will be assessed and defined as the completion of upper gastrointestinal endoscopy without the administration of a rescue sedative agent or more than two top-up doses of the trial drug in any 5-min period after initial administration. Sedation quality will be evaluated using the Modified Observer’s Assessment of Alertness/Sedation score. Adverse events will be recorded to evaluate safety. Discussion This study will determine the optimal dosage of remimazolam tosylate during upper gastrointestinal endoscopy and will describe its efficacy and safety. These findings may contribute to a more comfortable and safer experience for patients compared with that when the conventional sedative propofol is used. Trial registration ClinicalTrials.gov NCT04727034. Registered on February 18, 2021.

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BackgroundThis study explored the effectiveness of pre-operative intravenous injection of butorphanol in the alleviation of emergence agitation (EA) in patients undergoing functional endoscopic sinus surgery (FESS).MethodsPatients (n = 708) were randomized into two groups. The butorphanol group (Group B, n = 358) received butorphanol infusion (20 ug/kg) before anesthesia induction, while the control group (Group C, n = 350) received an equal volume of normal saline infusion. General anesthesia was induced with sufentanil, propofol, and rocuronium, and was maintained with sevoflurane and remifentanil. Vasoactive drugs maintained the hemodynamic indices within 20% of the baseline.ResultsThe incidence of EA was significantly lower in Group B than that in Group C (Group B vs. C: 24.3% vs. 31.4%, respectively; P = 0.034). The times to spontaneous breathing (26.5 min vs. 23.7 min, P = 0.011), verbal response (36.0 min vs. 33.4 min, P = 0.012), and extubation (31.0 min vs. 28.7 min, P = 0.025) were longer in Group B, and the grade of cough (0.33 vs. 0.43, P = 0.024) at extubation in Group B was lower than that in Group C (P = 0.024). The mean arterial pressure at the end of the operation (P = 0.004) and at 5 min after extubation (P = 0.008) was higher and hypotension was less prominent (0.6% vs. 2.6%, P = 0.030) in Group B.ConclusionPre-operative intravenous injection of butorphanol decreased the incidence of EA after FESS and provided smooth and hemodynamically stable emergence without extending the stay in post-anesthesia care unit.Clinical trial registrationhttps://www.clinicaltrials.gov/, identifier NCT03398759.

Introduction So far, the recovery quality after general anesthesia is still unsatisfied. Nalmefene is a drug to treat opioid overdose and reverse opioid actions. We aim to investigate the efficacy of nalmefene on optimizing the recovery quality of patients after general anesthesia. Methods It is a prospective, placebo-controlled, two-arm parallel groups, multicentre, double-blind, randomized (PPPMDR) clinical trial. The participants (n = 520) will be randomly assigned into two groups. Each patient will receive either: a single dose of nalmefene 0.25 µg/kg in the intervention group, or the same volume of 0.9% NaCl solution in the control group at the end of the surgery. The primary outcome will be the time interval between the end of anaesthesia and recovery endpoints achieved (Aldrete recovery score ≥ 9) in post-anesthesia care unit (PACU). The other variables are the time interval from the end of operation to extubation; Richmond Agitation Sedation Scale (RASS) score at extubation; the time at Montreal Cognitive Assessment Scale (MoCA) orientation score ≥ 5; visual analog scale (VAS) score and adverse effects including postoperative nausea and vomiting (PONV), and pruritus in PACU and 24 h postoperatively. Analysis This trial aims to study whether small dose of nalmefene can shorten the time from the end of surgery to Aldrete score ≥ 9 and improve opioid-induced side effects.This trial focuses on providing the reliable clinical evidence for satisfactory quality of recovery. Ethics and dissemination This clinical trial has been approved and supported by the ethics committee of the Renji Hospital, Shanghai Jiaotong University, School of Medicine (KY2020-150); Shanghai Tongren Hospital (2021–030-01);The First Affiliated Hospital of Guangxi Medical University (2021–032); and The First Affiliated Hospital of Zhengzhou University(2021-KY-0495–003). Analysis of the study results will be submitted to a peer-reviewed journal for publication. Trial registration ClinicalTrials.gov, NCT04713358, Registered on September 23, 2021.

Background: This study explored the effectiveness of preoperative intravenous injection of butorphanol in the alleviation of emergence agitation (EA) in patients undergoing functional endoscopic sinus surgery (FESS).Methods: Patients (n = 708) were randomized into two groups. The butorphanol group (Group B, n=358) received butorphanol infusion (20 ug/kg) before anaesthesia induction, while the control group (Group C, n=350) received an equal volume of normal saline infusion. General anaesthesia was induced with sufentanil, propofol and rocuronium, and was maintained with sevoflurane and remifentanil. Vasoactive drugs maintained the haemodynamic indices within 20% of the baseline.Results: The incidence of EA (Group B vs. C: 24.3 vs. 31.4%, P = 0.034). The times to spontaneous breathing (26.5 min vs. 23.7 min, P = 0.011), verbal response (36.0 min vs. 33.4 min, P = 0.012) and extubation (31.0 min vs. 28.7 min, P = 0.025) were longer in Group B, and the grade of cough (0.33 vs. 0.43, P = 0.024) at extubation in Group B was lower than that in Group C (P = 0.024). The mean arterial pressure at the end of the operation (P = 0.004) and at 5 min after extubation (P = 0.008) was higher and hypotension was less prominent (0.6% vs. 2.6%, P = 0.030) in Group B.Conclusions: Preoperative intravenous injection of butorphanol decreased the incidence of EA after FESS, and provided smooth and haemodynamically stable emergence without extending the stay in post-anaesthesia care unit.Trial registration: Clinicaltrials.gov, NCT03398759. Registered 21 December 2017, https://www.clinicaltrials.gov/ct2/show/NCT03398759?term=03398759&draw=2&rank=1