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Monitoring the nociception/antinociception balance for analgesic guidance during general anesthesia may improve the quality of anesthesia. The University Hospital of Lille (France) has developed an expert software system for automatic remifentanil administration based on the continuous monitoring of the Analgesia Nociception Index (MDoloris, France). We assessed the clinical efficacy and safety of the ANI-REMI-LOOP \"expert-system software\" during burn surgery in a monocentric randomized controlled trial. The trial was approved by the French Ethics Committee, and all patients gave written informed consent. From 2018 to 2022, 52 adults were randomized into two groups: manual remifentanil infusion (standard practice) or automatic remifentanil infusion (expert-system software) during BIS-guided propofol anesthesia at the burn center of the hospital. In the standard practice group, remifentanil administration was based on Minto's model and guided by the analgesia nociception index. In both groups, propofol was administered based on Schnider's model and guided by the BiSpectral Index (Covidien). The primary endpoint was the cumulative remifentanil dose administered during anesthesia and secondary endpoints were related to the clinical safety of automatic remifentanil administration with the incidence and duration of hypotension, bradycardia, hypertension or tachycardia related to nociception. After anesthesia, the endpoints were pain and analgesic requirements during 2 hours. A p value < 0.05 was considered statistically significant. Data are presented as median [1st to 3rd quartile]. The cumulative remifentanil dose was significantly lower in the automatic group 0.125 µg.kg-1.min-1 [0.106 to 0.149] vs. 0.152 µg.kg-1.min-1 [0.137 to 0.237], p = 0.004), and the cumulative proportion of time with hemodynamic impairment or reactivity was significantly lower in the expert-system automatic group 4.2% [2.5 to 5.7] vs. 19.4% [6.9 to 59.9], p = 0.010). There were no safety issues, and pain and analgesic requirements were similar in both groups after surgery. Automatic remifentanil administration demonstrated good clinical performances during propofol anesthesia for burn surgery. It is likely that these results can be extrapolated to any surgical setting under general anesthesia, but this needs to be tested with further randomized clinical trials.

Background Intraoperation hypotension (IOH) is commonly observed in patients undergoing surgery under general anesthesia, and even a brief episode of IOH can lead to unfavorable outcomes. To reduce the risk, blood pressure is closely measured during general anesthesia, and norepinephrine (NE) is frequently administered if hypotension is detected. Despite its routine application, information on the dose-exposure-response relationship of NE remains limited. Additionally, quantification of the influence of general anesthesia on the pharmacokinetics (PK) of NE is lacking. Objective In this study, we aimed to describe NE PK in healthy volunteers and the influence of general anesthesia on its PK. Methods A single-center, cross-over study was conducted in healthy volunteers. The volunteers received a step-up NE dosing scheme (0.04, 0.08, 0.12, 0.16 and 0.20 mcg –1 /kg –1 /min –1 ) first in the awake state and then under general anesthesia. General anesthesia was administered using a propofol/remifentanil Eleveld target-controlled infusion. During general anesthesia, a 30-second electrical stimulus was given as surrogate for surgical incision to the volunteers at each dosage step. Blood samples were drawn before the initial dosing and after each dosing step, and plasma NE, propofol and remifentanil concentrations were subsequently determined. A population PK model was developed using non-linear mixed effects modelling. Simulations were conducted to predict the plasma NE concentration in patients at different measured propofol concentrations. Results A total of 1219 samples were analyzed from 36 volunteers. A two-compartment model with a first-order elimination best described the data. Weight, age, and session effect (awake vs general anesthesia) were identified as relevant covariates on the clearance (CL) of NE. A 10% decrease in NE CL was observed after general anesthesia induction. This difference between sessions is better explained by the measured concentration of propofol, rather than the anticipated impact of cardiac output. The estimated post-stimulation NE concentration is 0.66 nmol/L –1 (95% CI 0.06–1.20 nmol/L –1 ) lower than the pre-stimulation NE concentration. Model simulation indicates that patients at a higher measured propofol concentration (e.g., 6 mcg/mL –1 ) exhibited higher NE concentrations (95% PI 18.10–43.89 nmol/L –1 ) than patients at a lower measured propofol concentration (e.g., 3 mcg/mL –1 ) (95% PI 16.81–38.91 nmol L –1 ). Conclusion The NE PK is well described with a two-compartment model with a first-order elimination. NE CL exhibiting a 10% decrease under general anesthesia, with this difference being attributed to the measured concentration of propofol. The impact of stimulation on NE PK under general anesthesia is very limited. Clinical Trials Registration Number NL9312.

Remimazolam's benefits for patients undergoing painless flexible fiberoptic bronchoscopy remain uncertain. We aimed to compare the efficacy and safety of remimazolam and dexmedetomidine in flexible fiberoptic bronchoscopy (FFB). Randomized controlled trial. University hospital. Between April 2021 and September 2022, patients undergoing painless flexible fiberoptic bronchoscopy were recruited. The patients were randomly assigned with a 1:1 ratio to remimazolam-remifentanil group (RR group) or dexmedetomidine-remifentanil group (DR group). The primary outcome was the procedure interruption rate during bronchoscopy. Secondary outcomes were hemodynamic changes, resuscitation time, rescue medication usage rate and dose, satisfaction scores of patients and bronchoscopists, operation-related complications, and adverse events. A total of 363 patients were included for final analysis. The interruption rates of bronchoscopy were 8.2 % in the RR group and 39.2 % in the DR group (P < 0.05). The rescue medication usage rate (4.4 % vs. 38.7 %, P < 0.05) and dose (1.51 ± 8.15 mg vs. 13.17 ± 18.86 mg, P < 0.05) were lower in the RR group compared with the DR group. The incidence of oxygen desaturation was significantly lower in the RR group than in the DR group (14.3 % vs. 44.2 %, P < 0.05). Hemodynamic changes in patients in the DR group were significant, with longer recovery time and lower satisfaction scores for both inpatients and bronchoscopists (P < 0.05), compared with the RR group. However, there were no significant differences between groups in terms of operation-related complications (P > 0.05) except for postoperative dizziness, which was more common in the DR group (P < 0.05). Remimazolam is effective and safe in painless flexible fiberoptic bronchoscopy. It allows a lower procedure interruption rate and incidence of oxygen desaturation, providing better hemodynamic stability compared to dexmedetomidine. •Remimazolam, an ultra-short-acting benzodiazepine, induced better sedation during bronchoscopy than dexmedetomidine.•Remimazolam had a better safety profile than that of dexmedetomidine.•Remimazolam anesthesia had higher bronchoscopist and patient satisfaction score.

We conducted a non-inferiority study to assess the postoperative quality of recovery (QoR) in elderly patients receiving ciprofol or propofol total intravenous anesthersia(TIVA)after elective laparoscopic major abdominal surgery, with QoR-15 scores as the main measure. A prospective, double-blind, randomized non-inferiority trial was conducted in the theater, post-anesthesia care unit (PACU), and the ward. 144 elderly patients (age ≥ 65 years) were randomly assigned to either the ciprofol group or the propofol group. The ciprofol group received continuous infusion of ciprofol with remifentanil, and the propofol group received infusion of propofol with remifentanil. The primary outcome was the QoR-15 on the first postoperative day (POD1), assessed in both intention-to-treat and per-protocol populations, with the mean difference between groups compared to a non-inferiority threshold of −8. Additional assessments included QoR-15 scores on POD2, 3, and 5 for both analysis sets. Other evaluated perioperative value factors included hemodynamic parameters and injection discomfort in the intention-to-treat analysis. A linear mixed model was utilized to examine the impact of group-time interactions on hemodynamic data and QoR-15. The QoR-15 scores on POD1 in the ciprofol group were non-inferior to those in the propofol group both in intention-to-treat set (mean [95 %CI], 95.9[93.7–98.2] vs. 95.6 [93.3–97.8]; mean difference [95 % CI], 0.4 [−2.8–3.5]; P<0.001 for noninferiority) and per-protocol set (mean [95 %CI], 96.7 [94.4–99.0] vs. 95.7 [93.4–98.0]; mean difference [95 % CI], 1.0 [−2.2–4.3]; P<0.001 for noninferiority). Comparable outcomes were noted on postoperative days 2, 3, and 5 following the procedure in both analysis sets. Additionally: compared with propofol group, the occurrence of injection pain was lower (2.8 % vs. 27.8 %, P < 0.001); the hypotension was less frequent (33.3 % vs. 54.2 %, P = 0.012); the bradycardia was more common (38.9 % vs. 23.6 %, P = 0.048). Ciprofol is not inferior to propofol in QoR. Ciprofol can be suitably administered to elderly patients undergoing elective laparoscopic major abdominal surgery. •Ciprofol is a novel intravenous anesthetic agent.•Ciprofol offers a comparable quality of recovery to propofol, with reduced injection pain, more stable intraoperative hemodynamics.•For elderly patients with cardiovascular diseases undergoing major laparoscopic surgery, ciprofol may be preferable to propofol.

Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15-0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery. A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction. Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62-0.79), anxiety level (OR, 0.77; 95% CI, 0.62-0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56-0.98) were identified as significant predictors associated with patient satisfaction. A subanesthetic dose of esketamine (0.15-0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery. ChiCTR2400080363.

Propofol and sevoflurane are two anesthetic agents widely used to induce and maintain general anesthesia (GA). Their intrinsic antinociceptive properties remain unclear and are still debated. To determine whether propofol presents stronger antinociceptive properties than sevoflurane using intraoperative clinical and experimental noxious stimulations and evaluating postoperative pain outcomes. A prospective randomized monocentric trial. Perioperative care. 60 adult patients with ASA status I to III who underwent elective abdominal laparoscopic surgery under GA were randomized either in propofol or sevoflurane group to induce and maintain GA. We used clinical and experimental noxious stimulations (intubation, tetanic stimulation) to assess the antinociceptive properties of propofol and sevoflurane in patients under GA and monitored using the NOL index, BIS index, heart rate, and mean arterial blood pressure. We measured the difference in the NOL index alterations after intubation and tetanic stimulation during either intravenous anesthesia (propofol) or inhaled anesthesia (sevoflurane). We also intraoperatively measured the NOL index and remifentanil consumption and recorded postoperative pain scores and opioid consumption in the post-anesthesia care unit. Intraoperative management was standardized by targeting similar values of depth of anesthesia (BIS index), hemodynamic (HR and MAP), NOL index values (below the threshold of 20), same multimodal analgesia and type of surgery. We found the antinociceptive properties of propofol and sevoflurane similar. The only minor difference was after tetanic stimulation: the delta NOL was higher in the sevoflurane group (39 ± 13 for the propofol group versus 47 ± 15 for sevoflurane; P = 0.04). Intraoperative and postoperative pain outcomes and opioid consumption were similar between groups. Despite a precise intraoperative experimental and clinical protocol using the NOL index, propofol does not provide a higher level of antinociception during anesthesia or analgesia after surgery when compared to sevoflurane. Anesthesiologists may prefer propofol over sevoflurane to reduce PONV or anesthesia-related pollution, but not for superior antinociceptive properties. •Propofol and sevoflurane's intrinsic antinociceptive properties are not yet clear.•Objective measurement of intraoperative nociception using the multiparametric NOL index helps precisely evaluate noxious stimulations.•Propofol and sevoflurane intraoperative antinociceptive properties were found to be similar.•No difference was observed in postoperative pain scores and consumption of analgesics.

Investigate the potential role of (mu-opioid receptor) and (catechol-O-methyltransferase enzyme) polymorphisms in postoperative acute, chronic and experimental thermal pain. A secondary analysis of 125 adult cardiac surgery patients that were randomized between fentanyl and remifentanil during surgery and genotyped. Patients in the fentanyl group with the high-pain sensitivity haplotype required less postoperative morphine compared with the average-pain sensitivity haplotype (19.4 [16.5; 23.0] vs 34.6 [26.2; 41.4]; p = 0.00768), but not to the low-pain sensitivity group (30.1 [19.1; 37.7]; p = 0.13). No association was found between haplotype and other pain outcomes or polymorphisms and the different pain modalities. haplotype appears to explain part of the variability in acute postoperative pain in adult cardiac surgery patients.

IntroductionMotor-evoked potentials (MEP) are widely used to mitigate the risk of nerve injury resulting from surgical manipulation. Infants are more susceptible to anaesthetics that suppress MEP because of the immaturity of their nervous structures. Current evidence of the impact of the interaction between a small dose of sevoflurane and propofol-based total intravenous anaesthesia (TIVA) on MEP in infants is controversial. This current study aims to evaluate the impact of the coadministration of low-dose sevoflurane with propofol-based TIVA on MEP in infants.Methods and analysisA randomised controlled study will be conducted at a single tertiary care children’s hospital in Japan between July 2024 and June 2029. Children between 35 and 87 weeks of postconceptual age undergoing spinal surgery requiring MEP under general anaesthesia will be enrolled in this study. The participants will be randomly allocated into two groups: propofol+remifentanil with (intervention group) or without (control group) low-dose sevoflurane (0.10–0.15 age-adjusted minimum alveolar concentration). MEP top-to-bottom amplitudes will be measured at two chronological points: T1 (first transcranial MEP (TcMEP) recording), T2 (second TcMEP recording) in the same patient. The primary and secondary endpoints will be a reduction in MEP amplitudes (T1–T2) in the right upper and lower extremities between the control and intervention groups, respectively. The sample size was calculated to be a total of 40 based on the preliminary data of 10 infants, which showed a 35% reduction in mean values of MEP amplitudes in the right adductor muscle (SD=31) with a 10% assumed dropout rate.Ethics and disseminationThe study protocol was approved by the Institutional Review Board of the Aichi Children’s Health and Medical Center (2022058). The results will be reported in a peer-reviewed journal at the relevant academic conference.Trial registration numberjRCT1041230094.

IntroductionEmergence agitation (EA), defined as acute postoperative restlessness after general anaesthesia, is a common complication in the post-anaesthesia care unit (PACU). The reported incidence of EA is nearly 30% in neurosurgical surgery, which bears tremendous risks for neurosurgical patients. Although current evidence suggests that remifentanil may reduce EA risk in non-cardiac settings, its preventive efficacy in patients undergoing intracranial surgery remains unclear.Methods and analysisIn this single-centre, randomised, double-blind, parallel-group prospective clinical trial, patients scheduled for elective craniotomy will be screened to confirm their eligibility. After surgery under general anaesthesia, patients will be assigned to groups to receive either remifentanil or placebo infusion on admission to the PACU. The remifentanil group will be given remifentanil infusion at a dose of 0.1 µg/(kg×min), whereas the control group will be given the same volume of normal saline. The primary outcome is the effect of remifentanil on EA incidence during the emergence period. Secondary outcomes include the following: time to regain consciousness, extubation time, total PACU duration, extubation comfort score measured by the modified Minogue Scale, postoperative pain intensity assessed using a Numerical Rating Scale, awakening quality and postoperative delirium assessed by alertness and orientation score, and a 3-Minute Diagnostic Interview for Confusion Assessment Method.Ethics and disseminationThe study protocol (V.4.0, dated 14 August 2025, No. 2025–0954) has been approved by the Institutional Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine and complies with the Declaration of Helsinki and relevant regulations for research involving human participants. Findings will be disseminated through peer-reviewed publications and conference presentations.Trial registration numberChiCTR2500096691.

Purpose This study aimed to compare the hemodynamic effects of remimazolam- and propofol-based total intravenous anesthesia in patients who underwent transcatheter aortic valve replacement. Methods This was a single-center, single-blind, randomized controlled trial set at Nara Medical University, Kashihara, Japan. We included 36 patients aged ≥ 20 years scheduled to undergo elective transfemoral transcatheter aortic valve replacement (TAVR) under general anesthesia. The participants were randomly assigned to the remimazolam and propofol groups ( n  = 18 each). Remimazolam- or propofol-based total intravenous anesthesia was initiated at 12 mg/kg/min or 2.5 mcg/mL via target-controlled infusion, respectively, along with remifentanil. After confirming the loss of consciousness, the administration rate was adjusted using electroencephalographic monitoring. The primary outcome was the rate of arterial hypotension, defined as a mean arterial pressure < 60 mmHg, from anesthesia induction until the beginning of the surgical incision. The total doses of ephedrine and phenylephrine were also assessed. Results During anesthesia induction, the arterial hypotension rates were 11.9% and 21.6% in the remimazolam and propofol groups, respectively ( P  = 0.01). The total dose of ephedrine was higher in the propofol group (14.4 mg) than in the remimazolam group (1.6 mg) ( P  < 0.001); however, the total dose of phenylephrine was not significantly different between the two groups (propofol 0.31 mg vs. remimazolam: 0.17 mg, P  = 0.10). Conclusion Remimazolam-based total intravenous anesthesia resulted in a lower hypotension rate than propofol-based total intravenous anesthesia during induction in patients undergoing TAVR. Remimazolam-based total intravenous anesthesia can be used safely during anesthetic induction in patients with severe aortic stenosis.