Neuromuscular end-point predictive capability of published rocuronium pharmacokinetic/pharmacodynamic models: An observational trial.

BACKGROUND: Objective neuromuscular monitoring remains the single most reliable method to ensure optimal perioperative neuromuscular management. Nevertheless, the prediction of clinical neuromuscular endpoints by means of Pharmacokinetic (PK) and Pharmacodynamic (PD) modelling has the potential to complement monitoring and improve perioperative neuromuscular management.s STUDY OBJECTIVE: The present study aims to assess the performance of published Rocuronium PK/PD models in predicting intraoperative Train-of-four (TOF) ratios when benchmarked against electromyographic TOF measurements. DESIGN: Observational trial. SETTING: Tertiary Belgian hospital, from August 2020 up to September 2021. PATIENTS AND INTERVENTIONS: Seventy-four patients undergoing general anaesthesia for elective surgery requiring the administration of rocuronium and subject to continuous EMG neuromuscular monitoring were included. PK/PD-simulated TOF ratios were plotted and synchronised with their measured electromyographic counterparts and their differences analysed by means of Predictive Error derivatives (Varvel criteria). MAIN RESULTS: Published rocuronium PK/PD models overestimated clinically registered TOF ratios. The models of Wierda, Szenohradszky, Cooper, Alvarez-Gomez and McCoy showed significant predictive consistency between themselves, displaying Median Absolute Performance Errors between 38% and 41%, and intra-individual differences (Wobble) between 14 and 15%. The Kleijn model outperformed the former with a lower Median Absolute Performance Error (16%, 95%CI [0.01; 57]) and Wobble (11%, 95%CI [0.01; 34]). All models displayed considerably wide 95% confidence intervals for all performance metrics, suggesting a significantly variable performance. CONCLUSIONS: Simulated TOF ratios based on published PK/PD models do not accurately predict real intraoperative TOF ratio dynamics. TRIAL REGISTRATION: NCT04518761 (clinicaltrials.gov), registered on 19 August 2020.

A survey on the availability, usage and perception of neuromuscular monitors in Europe.

PURPOSE: Neuromuscular blocking agents (NMBAs) are routinely administered to patients in a multiplicity of anesthetic settings. Absence of postoperative residual neuromuscular block is widely considered an anesthetic patient safety mandate. Despite the increasing availability of a wider range of commercial quantitative neuromuscular monitors, the availability and use of neuromuscular monitoring devices is deemed to be suboptimal even in countries with above-average health system ratings. The present study aims to more precisely characterize the perceived availability, cost sensitivity and usability of neuromuscular monitoring devices within European anesthesia departments. METHODS: A pre-registered internet-based survey assessing the availability, cost sensitivity and usability of neuromuscular monitoring devices was distributed as e-mail newsletter by the European Society of Anaesthesiology and Intensive Care (ESAIC) to all of its active full members. The survey was available online for a total of 120 days. RESULTS: Having targeted a total of 7472 ESAIC members, the survey was completed by a total of 692 anesthesiologists (9.3%) distributed across 37 different European countries. Quantitative monitors were reported to be proportionally more available than qualitative ones (87.6% vs. 62.6%, respectively), as well as in greater monitor-per-operating room ratios. Most anesthesiologists (60.5%) expressed moderate confidence in quantitative monitors, with artifactual recordings and inaccurate measurements being the most frequently encountered issues (25.9%). The commercial pricing of quantitative devices was considered more representative of a device's true value, when compared to qualitative instruments (average cost of €4.500 and €1.000 per device, respectively). CONCLUSION: The availability of quantitative NMM in European operating theaters has increased in comparison with that reported in previous decades, potentially indicating increasing monitoring rates. European anesthesiologists express moderate confidence in quantitative neuromuscular monitors, along with a sentiment of adequate pricing when compared to their qualitative counterparts. Trust in quantitative monitors is marked by caution and awareness for artifactual recordings, with a consequent expectation that developments focusing on accuracy, reliability and ergonomics of neuromuscular monitors be prioritized.

Goals, Expectations, and the Definition of Success for Neuromodulation for Pain According to Representatives of Neuromodulation Device Manufacturers.

Representatives of neuromodulation device manufacturers are expected to facilitate the relationship between patients and healthcare providers. Nevertheless, the goals, expectations, and definition of success for neuromodulation for pain have not yet been explored. Representatives present at the 2nd Joint Congress of the INS European Chapters in September 2021 completed a survey to ascertain their opinions about the goals to achieve with neuromodulation, the factors that they expect to change, and their definition of success for neuromodulation. In total, 39 representatives completed the survey. To provide excellent service for patients (22.4%), to become a trusted partner for physicians (21.5%), and to provide excellent service for physicians (20.7%) were the highest ranked goals. The most frequently reported factors that were expected to change were pain intensity (23.1%), patient satisfaction (19.7%), mobility/functioning (14.5%), and capacity to return to work (13.7%). Within the definitions of success, increased quality of life of the patient was stated in 21% of the definitions, closely followed by pain control (19.3%) and happiness/patient satisfaction (15.8%). The goals of representatives of neuromodulation device manufacturers seem to focus on ensuring a good relationship with physicians on the one hand and providing good service towards patients on the other hand, whereby pain control, quality of life, and patient satisfaction seem to be important for company representatives.

Atrial Fibrillation Global Changes after Pulmonary Vein and Posterior Wall Isolation: A Charge Density Mapping Study.

BACKGROUND: Non-contact charge density (CD) mapping allows a global visualization of left atrium (LA) activation and of activation patterns during atrial fibrillation (AF). The aim of this study was to analyze, with CD mapping, the changes in persistent AF induced by pulmonary vein isolation (PVI) and LA posterior wall isolation (LAPWI). METHODS: Patients undergoing PVI + LAPWI using the Arctic Front Advance PROTM cryoballoon system were included in the study. CD maps were created during AF at baseline, after PVI and after LAPWI. Three distinct activation patterns were identified in the CD maps: localized irregular activation (LIA), localized rotational activation (LRA) and focal centrifugal activation (FCA). LA maps were divided into the following regions: anterior, septal, lateral, roof, posterior, inferior. RESULTS: Eleven patients were included, with a total of 33 maps and 198 AF regions analyzed. Global and regional AF cycle lengths significantly increased after PVI and LAPWI. Baseline analysis demonstrated higher LIA, LRA and FCA numbers in the posterior and anterior regions. After PVI, there was no change in LIA, LRA and FCA occurrence. After PVI + LAPWI, a significant decrease in LRA was observed with no difference in LIA and FCA occurrence. In the regional analysis, there was a significant reduction in the LIA number in the inferior region, in the LRA number in the roof and posterior regions and in the FCA number in the lateral region. CONCLUSIONS: A global reduction in the LRA number was observed only after PVI + LAPWI; it was driven by a reduction in rotational activity in the roof and posterior regions.

Propofol for Induction and Maintenance of Anesthesia in Patients With Brugada Syndrome: A Single-Center, 25-Year, Retrospective Cohort Analysis.

BACKGROUND: Propofol administration in patients with Brugada syndrome (BrS) is still a matter of debate. Despite lacking evidence for its feared arrhythmogenicity, up to date, expert cardiologists recommend avoiding propofol. The main aim of this study is to assess the occurrence of malignant arrhythmias or defibrillations in patients with BrS, during and 30 days after propofol administration. The secondary aim is to investigate the occurrence of adverse events during propofol administration and hospitalization, as the 30-day readmission and 30-day mortality rate. METHODS: We performed a retrospective cohort study on patients with BrS who received propofol anytime from January 1, 1996 to September 30, 2020. Anesthesia was induced by propofol in both groups. In the total intravenous anesthesia (TIVA) group, anesthesia was maintained by propofol, while in the BOLUS group, volatile anesthesia was provided. The individual anesthetic charts and the full electronic medical records up to 30 postprocedural days were scrutinized. RESULTS: One hundred thirty-five BrS patients who underwent a total of 304 procedures were analyzed. The TIVA group included 27 patients for 33 procedures, and the BOLUS group included 108 patients for 271 procedures. In the TIVA group, the median time of propofol infusion was 60 minutes (interquartile range [IQR] = 30-180). The estimated plasma or effect-site concentration ranged between 1.0 and 6.0 µg·mL-1 for target-controlled infusion (TCI). The infusion rate for manually driven TIVA varied between 0.8 and 10.0 mg·kg-1·h-1. In the BOLUS group, the mean propofol dose per kilogram total body weight was 2.4 ± 0.9 mg·kg-1. No malignant arrhythmias or defibrillations were registered in both groups. The estimated 95% confidence interval (CI) of the risk for malignant arrhythmias in the BOLUS and TIVA groups was 0-0.011 and 0-0.091, respectively. CONCLUSIONS: The analysis of 304 anesthetic procedures in BrS patients, who received propofol, either as a TIVA or as a bolus during induction of volatile-based anesthesia, revealed no evidence of malignant arrhythmias or defibrillations. The present data do not support an increased risk with propofol-based TIVA compared to propofol-induced volatile anesthesia. Prospective studies are needed to investigate the electrophysiologic effects of propofol in BrS patents.

Electrocardiographic Effects of Propofol versus Etomidate in Patients with Brugada Syndrome.

BACKGROUND: Brugada Syndrome is an inherited arrhythmogenic disease, characterized by the typical coved type ST-segment elevation in the right precordial leads from V1 through V3. The BrugadaDrugs.org Advisory Board recommends avoiding administration of propofol in patients with Brugada Syndrome. Since prospective studies are lacking, it was the purpose of this study to assess the electrocardiographic effects of propofol and etomidate on the ST- and QRS-segments. In this trial, it was hypothesized that administration of propofol or etomidate in bolus for induction of anesthesia, in patients with Brugada Syndrome, do not clinically affect the ST- and QRS-segments and do not induce arrhythmias. METHODS: In this prospective, double-blinded trial, 98 patients with established Brugada syndrome were randomized to receive propofol (2 to 3 mg/kg) or etomidate (0.2 to 0.3 mg/kg) for induction of anesthesia. The primary endpoints were the changes of the ST- and QRS-segment, and the occurrence of new arrhythmias upon induction of anesthesia. RESULTS: The analysis included 80 patients: 43 were administered propofol and 37 etomidate. None of the patients had a ST elevation greater than or equal to 0.2 mV, one in each group had a ST elevation of 0.15 mV. An ST depression up to -0.15mV was observed eleven times with propofol and five with etomidate. A QRS-prolongation of 25% upon induction was seen in one patient with propofol and three with etomidate. This trial failed to establish any evidence to suggest that changes in either group differed, with most percentiles being zero (median [25th, 75th], 0 [0, 0] vs. 0 [0, 0]). Finally, no new arrhythmias occurred perioperatively in both groups. CONCLUSIONS: In this trial, there does not appear to be a significant difference in electrocardiographic changes in patients with Brugada syndrome when propofol versus etomidate were administered for induction of anesthesia. This study did not investigate electrocardiographic changes related to propofol used as an infusion for maintenance of anesthesia, so future studies would be warranted before conclusions about safety of propofol infusions in patients with Brugada syndrome can be determined.

Safe single-dose administration of propofol in patients with established Brugada syndrome: a retrospective database analysis.

BACKGROUND: Propofol is an anesthetic drug with a very attractive pharmacokinetic profile, which makes it the induction agent of choice, especially in day-case surgery. Data on its potential proarrhythmic effects in patients with Brugada syndrome (BS) patients are still lacking. The aim of our study was to investigate whether a single dose of propofol triggered any adverse events in consecutive high-risk patients with BS. METHODS: All consecutive patients with BS having undergone an implantable cardiac defibrillator implantation under general anesthesia were eligible for this study. The anesthetic chart of each patient was reviewed, and the occurrence of malignant arrhythmic events as well as the need for defibrillation during induction and maintenance of anesthesia was investigated. Further monitoring of the patient comprised five-lead electrocardiogram (ECG), pulse oxymetry, and continuous carbon dioxide monitoring through side sampling from the ventilator tubes. Anesthesia was induced with propofol and sufentanyl. Injection of propofol occurred in a single-shot bolus-as often performed by most anesthetists-over a few seconds. Anesthesia was maintained with volatile anesthetics (sevoflurane or desflurane) in an oxygen-air mixture. RESULTS: From 1996 to 2011, 57 high-risk patients with BS (35 males; mean age: 43 ± 16 years) underwent an automated implantable cardioverter defibrillator implantation at our center using propofol as induction drug of general anesthesia. Three patients had a history of spontaneous type I ECG, three had aborted sudden death, and 51 had a history of recurrent or unexplained syncope. The induction dose ranged between 0.8 mg/kg and 5.0 mg/kg (2.2 ± 0.7 mg/kg). Only one case received propofol to maintain anesthesia. The surgical procedure involved an anesthetic period of 75 ± 25 minutes. No patient developed a malignant rhythm during induction and maintenance of anesthesia. All patients were then safely discharged from the postanesthetic care unit after 1 hour. No adverse events were noticed during the recovery phase. In our study, administration of a single-dose propofol in patients with BS was safe. Nevertheless, extreme caution is still recommended when conducting general anesthesia in patients with BS, especially if BS patients are sedated with propofol for longer periods.