European Journal of Anaesthesiology最新文献

Background: No relevant clinical studies have investigated how epidural catheter design influences the transmeningeal flux of drugs.

Objective: To compare the analgesic outcomes between single-orifice and multiorifice wire-reinforced catheters following dural puncture epidural (DPE) for labour analgesia.

Design: Prospective double-blind randomised controlled study.

Setting: Shanghai First Maternity and Infant Hospital.

Patients: Between 1 September and 27 October 2024 healthy, nulliparous women with singleton pregnancies, cervical dilation of 2 to 5 cm, and requesting neuraxial analgesia were randomised to receive either a single-orifice or multiple-orifice polyurethane wire-reinforced epidural catheter as as part of the DPE technique along with a 25-G spinal needle.

Intervention: Epidural analgesia was initiated following DPE with 12 ml of 0.1% ropivacaine and 0.3 μg ml-1 sufentanil injected manually in two divided doses of 6 ml. Maintenance was then provided via programmed intermittent epidural boluses of the same solution, delivered as 10 ml every 40 min at an infusion rate of 360 ml h-1.

Main outcome measures: The primary endpoint was the time required to achieve a numeric rating scale pain score 3 or less following the initial bolus.

Results: Of 136 randomised participants, 131 were included in the analysis. Adequate analgesia was achieved significantly faster with single-orifice catheters than with multiorifice catheters, hazard ratio (HR) and 95% confidence intervals (CI) = 1.72 (1.17 to 2.53), P = 0.003. Post hoc sensitivity analysis confirmed these results, HR = 1.79 (1.19 to 2.71), P = 0.005.The median time (95% CI) to adequate analgesia was 11.0 (10.0 to 13.0) min for single-orifice and 14.0 (12.0 to 18.0) min for multiorifice catheters (P = 0.003). The single-orifice group demonstrated higher rates of adequate analgesia (89.2 vs. 72.7%, P = 0.02) and bilateral S2 sensory blockade (95.4 vs. 83.3%, P = 0.03) at 20 min, with no significant differences in other parameters.

Conclusions: DPE using a 25-G spinal needle and with a single-orifice catheter produced a significantly faster onset of analgesia than DPE with a multiorifice catheter during labour initiation.

Trial registration: Chinese Clinical Trial Registry (No: ChiCTR2400088640; Principal investigator: Yu Zang; Registration date: 22 August 2024).

Background: The combination of short- and long-acting local anaesthetics is traditionally associated with reduced block duration, though evidence remains inconsistent.

Objectives: To investigate the effects of a fixed or reduced dose of a long-acting local anaesthetic (ropivacaine) mixed with a short-acting agent (lidocaine-epinephrine) on duration of analgesia and sensory onset time in lateral infraclavicular blocks.

Design: Randomised, blinded, active-controlled superiority trial.

Setting: A tertiary hospital in the Capital Region of Denmark, from 18 April to 23 November 2024.

Patients: Seventy-eight patients undergoing hand surgery under lateral infraclavicular brachial plexus nerve block.

Intervention: Patients were allocated to three groups: R150: 30 ml ropivacaine 5 mg ml -1 , R100-L200: 20  ml ropivacaine 5 mg ml -1 + 10 ml lidocaine-epinephrine 20 mg ml -1 + 5 μg ml -1 and R150-L200: 20 ml ropivacaine 7.5 mg ml -1 + 10 ml lidocaine-epinephrine 20 mg ml -1 + 5 μg ml -1 .

Main outcome measures: The primary outcome was duration of analgesia, and secondary outcomes included sensory onset time.

Results: The duration of analgesia was 847 (152) min in the R150 group, 536 (198) min in the R100-L200 group, and 671 (234) min in the R150-L200 group. Compared with that in the R150 group, the mean duration of analgesia was reduced by 311 min (95% confidence interval [CI], 212 to 411; P  < 0.001) in the R100-L200 group and by 177 min (95% CI, 64 to 289; P = 0.003) in the R150-L200 group. The difference between the R100-L200 and R150-L200 groups was not statistically significant after adjustment for multiple testing (135 min; 95% CI, 13 to 257; P  = 0.031). Sensory onset times ranged insignificantly from 17 to 18 min across groups.

Conclusion: Mixing lidocaine-epinephrine with ropivacaine significantly shortened the duration of analgesia by up to 5 h without affecting the sensory onset time. This effect was independent of the ropivacaine dose.

Trial registration number: ClinicalTrials.gov identifier: NCT06381622.

Background: We have previously introduced a long-acting, nondepolarising, neuromuscular blocking agent, p NMB ( para -neuromuscular blocker). However, its neuromuscular, haemodynamic and autonomic effects as well as reversibility were not fully characterized.

Objective: We compared p NMB to rocuronium and tested the hypotheses that p NMB has a fast-onset, is long-acting, and its effects are reversed by sugammadex.

Design: Animal study.

Setting: Laboratory from January 2021 to February 2025.

Participants: Thirty-three adult male Sprague-Dawley rats.

Interventions: Rats were anesthetised and mechanically ventilated. Stimulating electrodes were attached to the sciatic and vagus nerves. Parasympathetic nerve activity was measured by vagal-induced bradycardia and sympathetic nerve activity by the nicotine pressor response.

Main outcome measures: Mechanomyography, mean arterial pressure (MAP) and heart rate (HR).

Results: Rocuronium and p NMB inhibited muscle twitch dose-dependently with effective dose (ED)50s (50% inhibition) of 0.28 (95% confidence interval (CI), 0.25 to 0.31) mg/kg, n  = 6, and 1.05 (95% CI, 0.93 to 1.20) mg/kg, n  = 6, respectively. Rocuronium and p NMB, at doses up to 3 mg/kg, had no effect on HR. Rocuronium 0.7 mg/kg and p NMB 6 mg/kg had no effect on MAP, mean ± SD, 153 ± 12 vs. 154 ± 14 mmHg, n  = 4, P  = 0.61, or decreased MAP 147 ± 9 vs. 72 ± 9 mmHg, n  = 4, P  < 0.01, respectively. Both rocuronium and p NMB were parasympatholytic with ED50s of 0.08 (95% CI, 0.06 to 0.09) mg/kg, n  = 5, and 0.18 (95% CI, 0.14 to 0.22) mg/kg, n  = 7, respectively. Rocuronium 0.7 mg/kg was not sympatholytic whereas p NMB 6 mg/kg was. Both rocuronium 0.7 mg/kg and p NMB 6 mg/kg decreased MAP in the presence of nicotine. Onset times of rocuronium 0.7 mg/kg and p NMB 6 mg/kg did not differ ( P  = 0.22). Rocuronium 0.7 mg/kg inhibited twitch for approximately 8 min, whereas p NMB 6 mg/kg inhibited twitch at a steady 80% for 60 min after administration. Sugammadex 10.9 mg/kg reversed the p NMB 3 mg/kg twitch blockade of 92.5% (95% CI, 85.9% to 99%), n  = 6.

Conclusions: The nondepolarising NMBA, p NMB, had a fast-onset similar to rocuronium and was long-acting and reversible by sugammadex. Both rocuronium and p NMB had autonomic effects that were apparent at subparalytic doses and decreased blood pressure in the presence of nicotine. When administered alone, rocuronium did not decrease MAP whereas p NMB caused a marked hypotension. Neither NMBA affected HR. These findings are limited to rats, and generalisability to other animal species and humans is unknown.

Registration: University of Missouri IACUC (#9750, #40189), Columbia, Missouri, USA.

Background: Activation of mast cells and systemic histamine release are major side effects of intravenously administered neuromuscular blocking agents (NMBAs). Mas-related G protein-coupled receptor-X2 (MRGPRX2) plays a key role in mediating anaphylactoid reactions.

Objective: To explore the mechanism of acute anaphylactic shock induced by muscle relaxants through the typical shock cases.

Design: Case report and case control study.

Patients: A 68-year-old male patient (80 kg) underwent surgical treatment in September 2023 and developed anaphylactic shock during anaesthesia induction.

Methods: A trial was conducted to evaluate the patient who experienced anaphylactic shock during the peri-operative period in comparison to control patients. The levels of MRGPRX2 and total immunoglobulin E (IgE) were measured in patient plasma, along with allergic mediators such as histamine and tryptase. Mast cell activation assay was performed to assess degranulation effectiveness by measuring β-hexosaminidase, histamine release, and calcium influx. Additionally, mast cell activation by peri-operative drugs was investigated. Local inflammatory experiments were conducted in a mouse model to evaluate rocuronium bromide-induced allergic reactions. Finally, MRGPRB2-CKO mice and siRNA silencing were used to elucidate the mechanism of rocuronium-induced anaphylactic shock.

Results: Plasma analysis of the patient experiencing anaphylaxis revealed normal total IgE levels (38.4 IU ml -1 ) but significantly elevated histamine concentration (53.78 ng ml -1 ). The MRGPRX2 concentration (52.22 ng ml -1 ) in this patient was markedly higher than the negative control group (16.40 ng ml -1 ). Serum-activated mast cell assays demonstrated that the anaphylaxis patient's plasma induced a significant release of β-hexosaminidase, calcium, and histamine from mast cells (significantly higher than the histamine levels naturally present in the plasma). Drug-activated mast cell experiments confirmed that rocuronium bromide triggered dose-dependent mast cell activation, leading to MCP-1, histamine, and calcium release. Local paw oedema experiments in mice further validated that rocuronium bromide induced local allergic reactions. Using MRGPRB2-CKO mice and siRNA silencing, we determined that rocuronium bromide-induced anaphylactic shock was mediated through MRGPRX2 activation, resulting in mast cell degranulation.

Conclusion: This study highlights the critical role of MRGPRX2 in rocuronium bromide-induced anaphylactic shock. In vitro diagnosis of MRGPRX2 levels may provide new criteria for reducing intra-operative risks.

Trial registration: The clinical trial was registered at the China Clinical Trial Registration Center (Registration Number: ChiCTR2300077364).

Background: The relationship between the residual amount of rocuronium and the dose of sugammadex required to reverse neuromuscular blockade (NMB) remains unclear.

Objectives: To determine the required dose of sugammadex based on the estimated residual rocuronium in the body using pharmacokinetic simulation and evaluate the reversal of NMB using sugammadex.

Design: Observational study.

Setting: Single-centre, randomised, controlled, four-group, single-blind study conducted at Osaka University Hospital, Japan.

Patients: Patients without cardiac, hepatic, renal or neuromuscular disorders scheduled for elective surgery.

Main outcome measures: For induction, 0.6 mg kg -1 rocuronium was administered. During maintenance, the effect site concentration of rocuronium was maintained at greater than 1 μg ml -1 . The residual amount of rocuronium in the body was calculated postoperatively through pharmacokinetic simulation. Considering the ratio of sugammadex to rocuronium molecules, patients were divided into four groups based on sugammadex dose: control (2 mg kg -1 ), and four, six and eight times the residual amount of rocuronium. Sugammadex was administered shortly after surgery, and the recovery time from administration of sugammadex to the train-of-four (TOF) ratio of 0.9 was recorded.

Results: Overall, 123 patients were analysed and successfully extubated, and no signs of recurarisation were observed. Regardless of the sugammadex dose (7.57 ± 2.35 vs. 4.08 ± 0.16 vs. 6.01 ± 0.19 vs. 8.00 ± 0.23 mg kg -1 , P  < 0.01), no significant differences in recovery times were observed among the groups (142 ± 74 vs. 161 ± 98 vs. 152 ± 82 vs. 120 ± 49 s, P  = 0.21).

Conclusion: Based on pharmacokinetic simulation, all patients successfully recovered from NMB using rocuronium, and excellent recovery profiles were achieved.

Background: Emergence agitation is common after nasal surgery under general anaesthesia. Remimazolam, a novel ultra-short-acting benzodiazepine, allows haemodynamic stability and prompt postoperative recovery, but the specific impact of remimazolam on emergence agitation is not well understood.

Objectives: The primary aim of this study was to compare the effects of remimazolam-based total intravenous anaesthesia (TIVA) and sevoflurane-based volatile induction and maintenance of anaesthesia (VIMA) on the occurrence of emergence agitation.

Design: A prospective, randomised, assessor-blinded clinical trial.

Setting: A single-centre study in a university-affiliated tertiary hospital.

Participants: Ninety-eight adults undergoing nasal surgery under general anaesthesia.

Interventions: Patients were randomised into two groups. The Sevoflurane group ( n  = 49) received VIMA with sevoflurane and nitrous oxide, while the Remimazolam group ( n  = 49) received TIVA with remimazolam and remifentanil.

Main outcome measures: The primary outcome was the occurrence of emergence agitation, which was evaluated using the Richmond Agitation-Sedation Scale and the Riker Sedation-Agitation Scale. The secondary outcomes were immediate complications after extubation and postoperative pain, and the interval between discontinuation of anaesthesia and extubation.

Results: Emergence agitation, as measured by the Richmond Agitation-Sedation Scale, occurred in six of 49 patients (12.2%) in the Sevoflurane group and none (0.0%) in the Remimazolam group. The risk difference was 12.2 (95% CI, 3.0 to 21.4, P  = 0.008). The occurrence measured by the Riker Sedation-Agitation Scale was identical to that with the Richmond Agitation-Sedation Scale. Coughing was more frequent in the Sevoflurane group, 53.1 vs. 12.2%, risk difference = 40.8 (95% CI, 24.0 to 57.5, P  < 0.001). In addition, the interval between discontinuation of anaesthesia and extubation was lower in the Remimazolam group than the Sevoflurane group (9.00 ± 4.25 min vs. 12.18 ± 4.18 min, respectively, P <  0.001).

Conclusion: The occurrence of emergence agitation in adult patients after nasal surgery under general anaesthesia can be significantly reduced using remimazolam-based TIVA.

Trial registration: Clinical Research Information Service (KCT0007387).

Background: Remimazolam tosylate, a novel short-acting benzodiazepine, is increasingly being used in general anaesthesia, but its role in the incidence of postoperative delirium is uncertain, particularly in frail elderly patients.

Objective: To compare the effects of remimazolam tosylate with propofol on the incidence of postoperative delirium in frail elderly patients undergoing hip surgery.

Design: Randomised, single-centre, single-blind controlled trial.

Setting: A tertiary teaching hospital in China, conducted from March to December 2023.

Patients: Frail elderly patients (Reported Edmonton Frail Scale Score ≥ 6) undergoing hip surgery under general anaesthesia.

Interventions: Patients were randomly assigned to either the propofol or remimazolam group. Both groups received total intravenous anaesthesia following a standardised protocol with either propofol or remimazolam tosylate for induction and maintenance.

Main outcome measures: The primary outcome was the incidence of postoperative delirium within three postoperative days, assessed twice daily using the 3D Confusion Assessment Method (3D-CAM). The secondary outcomes included the quality of postoperative recovery and adverse events.

Result: A total of 136 patients were enrolled. The incidence of postoperative delirium was significantly lower in the remimazolam group than in the propofol group [3 of 68 (4.4%) vs. 12 of 68 (17.6%), risk differece (RD) -13.2%, 95% CI -23.5% to -2.9%, relative risk (RR) 0.25, 95% CI 0.074 to 0.847, NNT 7.6, P  = 0.0143]. The incidence of hypotension after induction was also lower in the remimazolam group [16 of 68 (23.5%) vs. 32 of 68 (47.1%), RD -23.5%, 95%CI -39.1% to -8.0%, RR 0.5, 95% CI 0.304 to 0.822, NNT 4.3, P  = 0.004], with fewer patients requiring vasopressors [55 of 68 (80.9%) vs. 66 of 68 (97.1%), RD -16.2%, 95% CI -26.3 to -6.0, RR 0.8, 95% CI 0.737 to 0.942, NNT 6.2, P  = 0.003]. Notably, the remimazolam group exhibited significantly less burst suppression compared with the propofol group, both in terms of burst suppression time (2.2 s [0 to 17.6] vs. 21.9 s [2.3 to 115.3] median difference = 11.98 s, 95% CI 2.44 to 27.90, P  < 0.001) and its proportion relative to the total surgery time (0.3‰ [0 to 2.1] vs. 2.8‰ [0.2 to 14.7], median difference 1.30‰, 95% CI 0.27 to 3.34, P  < 0.001).

Conclusion: In frail elderly patients, remimazolam tosylate was associated with a lower incidence of postoperative delirium compared with propofol.

Trial registration: Chinese Clinical Trial Registry, Chictr.org.cn, identifier: ChiCTR2300068632.

Background: Breast surgery is a cornerstone in the treatment of breast cancer but can cause persistent or worsening pain lasting beyond 3 months. Perioperative risk factors for chronic pain remain an area of ongoing research.

Objective: To assess the incidence of chronic pain following breast surgery and identify its associated factors.

Design: A retrospective cohort study.

Setting: A single high-volume tertiary medical centre.

Patients: Women undergoing first-time unilateral breast surgery as part of breast cancer treatment, without pre-existing chronic pain, between January 2020 and September 2022.

Main outcome measures: The incidence of chronic postoperative pain at 3 and 6 months, pain scores, perioperative and in-hospital analgesic use, and predictive factors related to anaesthetic and treatment modalities.

Methods: Univariable and multivariable analysis of peri-operative data associated with chronic postoperative pain at 3 and 6 months. A multivariable model was constructed by stepwise selection of data.

Results: Chronic pain was reported in 32% (95% confidence interval (CI), 28.8 to 35.4%) of patients at 3 months and in 39% (95% CI, 35.9 to 42.2%) at 6 months postoperatively. During postanaesthetic care, 31% of patients recorded a pain score above four on the numeric rating scale (NRS), while 3% reported a score above seven. On subsequent days, the mean pain score fell below one. The use of sufentanil and propofol during general anaesthesia was strongly associated with a lower incidence of pain at 3 months, odds ratio (OR) 0.548 (95% CI 0.381 to 0.788) P  = 0.0012, as well as sentinel node biopsy, OR 0.520 (95% CI 0.274 to 0.988) P  = 0.0459. Adjuvant radiotherapy, OR 3.294 (95% CI 1.610 to 6.741) P  = 0.0011, and the presence of chronic pain at 3 months, OR 10.706 (95% CI 7.399 to 15.489) P  < 0.0001, were the strongest predictors of persistent pain at 6 months. Mastectomy, OR 0.610 (95% CI 0.456 to 0.817) P  = 0.0009, and age, OR 0.983 (95% CI 0.972 to 0.995) P  = 0.0051, were significantly associated after model construction.

Conclusions: Multiple factors are associated with chronic pain following breast surgery. While perioperative factors play a role, long-term treatment modalities also significantly influence its occurrence.

Background: Anaesthesiology and intensive care use monitoring to identify patients in danger of deterioration. Traditionally, trends and early warning scores allow clinicians to predict deterioration with moderate reliability. Reduced mean arterial blood pressure has been associated with complications, and models have been sought to predict its value. Machine learning methods with complex inputs have been used for predictive monitoring in hospital care.

Objectives: This study evaluates whether machine learning can predict mean arterial pressure (MAP) from previous values.

Design: This is a monocentre, retrospective, exploratory, observational cohort study using the MIMIC-III-WDB, VitalDB and an internal study centre dataset, training machine learning models on adult patients with invasively measured blood pressure (IBP) as input during an observation window up to 20 min before the prediction horizon (5 to 20 min).

Setting: Kepler University Hospital, Linz, Austria.

Participants: Two thousand three hundred and forty-six patients from the internal dataset, 4741 patients from MIMIC-III-WDB and 3357 patients from VitalDB were analysed.

Main outcome measures: The primary endpoint was model performance in predicting whether MAP would fall below 65 mmHg in a given time frame. In a secondary analysis, we restricted the input set to stable patients with current MAP above 65 mmHg.

Results: Models using the complete training data achieved receiver operating characteristic area under the curves (ROC AUCs) of 0.963, 0.946, 0.934 and 0.923 on the internal dataset for 5, 10, 15 and 20 min of prediction horizon, respectively, and 0.856, 0.837, 0.821 and 0.804 in the secondary analysis. The maximum difference of ROC AUC to baseline measurement (ROC AUC of last measured MAP as trivial estimator) was 0.006 for the complete training data and 0.051 for stable patients. The prediction of MAP may allow clinicians to intervene in time before MAP deterioration becomes clinically relevant.

Conclusion: Predicting MAP below 65 mmHg within 5, 10, 15 and 20 min for patients with and without a MAP above 65 mmHg is possible and requires only MAP as input for machine learning models.

Trial registration: ClinicalTrials.gov (NCT05471193).