A Practical Dosing Algorithm for Deep Neuromuscular Blockade during Total Intravenous Anesthesia: ROCURITHM.

BACKGROUND: The number of trials investigating the effects of deep neuromuscular blockade (NMB) on surgical conditions and patient outcomes is steadily increasing. Consensus on which surgical procedures benefit from deep NMB (a posttetanic count [PTC] of 1 to 2) and how to implement it has not been reached. The European Society of Anaesthesiology and Intensive Care does not advise routine application but recommends use of deep NMB to improve surgical conditions on indication. This study investigates the optimal dosing strategy to reach and maintain adequate deep NMB during total intravenous anesthesia. METHODS: Data from three trials investigating deep NMB during laparoscopic surgery with total intravenous anesthesia (n = 424) were pooled to analyze the required rocuronium dose, when to start continuous infusion, and how to adjust. The resulting algorithm was validated (n = 32) and compared to the success rate in ongoing studies in which the algorithm was not used (n = 180). RESULTS: The mean rocuronium dose based on actual bodyweight for PTC 1 to 2 was (mean ± SD) 1.0 ± 0.27 mg · kg-1 ·h-1 in the trials, in which mean duration of surgery was 116 min. An induction dose of 0.6 mg ·kg-1 led to a PTC of 1 to 5 in a quarter of patients after a mean of 11 min. The remaining patients were equally divided over too shallow (additional bolus and direct start of continuous infusion) or too deep; a 15-min wait after PTC of 0 for return of PTC to 1 or higher. Using the proposed algorithm, a mean 76% of all 5-min measurements throughout surgery were on target PTC 1 to 2 in the validation cohort. The algorithm performed significantly better than anesthesiology residents without the algorithm, even after a learning curve from 0 to 20 patients (42% on target, P ≤ 0.001, Cohen's d = 1.4 [95% CI, 0.9 to 1.8]) to 81 to 100 patients (61% on target, P ≤ 0.05, Cohen's d = 0.7 [95% CI, 0.1 to 1.2]). CONCLUSIONS: This study proposes a dosing algorithm for deep NMB with rocuronium in patients receiving total intravenous anesthesia.

Machine learning based analysis and detection of trend outliers for electromyographic neuromuscular monitoring.

PURPOSE: Neuromuscular monitoring is frequently plagued by artefacts, which along with the frequent unawareness of the principles of this subtype of monitoring by many clinicians, tends to lead to a cynical attitute by clinicians towards these monitors. As such, the present study aims to derive a feature set and evaluate its discriminative performance for the purpose of Train-of-Four Ratio (TOF-R) outlier analysis during continuous intraoperative EMG-based neuromuscular monitoring. METHODS: Patient data was sourced from two devices: (1) Datex-Ohmeda Electromyography (EMG) E-NMT: a dataset derived from a prospective observational trial including 136 patients (21,891 TOF-R observations), further subdivided in two based on the type of features included; and (2) TetraGraph: a clinical case repository dataset of 388 patients (97,838 TOF-R observations). The two datasets were combined to create a synthetic set, which included shared features across the two. This process led to the training of four distinct models. RESULTS: The models showed an adequate bias/variance balance, suggesting no overfitting or underfitting. Models 1 and 2 consistently outperformed the others, with the former achieving an F1 score of 0.41 (0.31, 0.50) and an average precision score (95% CI) of 0.48 (0.35, 0.60). A random forest model analysis indicated that engineered TOF-R features were proportionally more influential in model performance than basic features. CONCLUSIONS: Engineered TOF-R trend features and the resulting Cost-Sensitive Logistic Regression (CSLR) models provide useful insights and serve as a potential first step towards the automated removal of outliers for neuromuscular monitoring devices. TRIAL REGISTRATION: NCT04518761 (clinicaltrials.gov), registered on 19 August 2020.

Good clinical research practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents III: The 2023 Geneva revision.

The set of guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents was developed following an international consensus conference in Copenhagen in 1996 (Viby-Mogensen et al., Acta Anaesthesiol Scand 1996, 40, 59-74); the guidelines were later revised and updated following the second consensus conference in Stockholm in 2005 (Fuchs-Buder et al., Acta Anaesthesiol Scand 2007, 51, 789-808). In view of new devices and further development of monitoring technologies that emerged since then, (e.g., electromyography, three-dimensional acceleromyography, kinemyography) as well as novel compounds (e.g., sugammadex) a review and update of these recommendations became necessary. The intent of these revised guidelines is to continue to help clinical researchers to conduct high-quality work and advance the field by enhancing the standards, consistency, and comparability of clinical studies. There is growing awareness of the importance of consensus-based reporting standards in clinical trials and observational studies. Such global initiatives are necessary in order to minimize heterogeneous and inadequate data reporting and to improve clarity and comparability between different studies and study cohorts. Variations in definitions of endpoints or outcome variables can introduce confusion and difficulties in interpretation of data, but more importantly, it may preclude building of an adequate body of evidence to achieve reliable conclusions and recommendations. Clinical research in neuromuscular pharmacology and physiology is no exception.

Evaluation of continuous wound infusion with local analgesics in postoperative renal transplantation patients: A retrospective study.

Objectives: The objective is to evaluate the efficacy of the continuous wound infusion (CWI) with Ropivacaine (naropeine 2 mg/ml) on postoperative pain, analgesics consumption, and bowel function in renal transplantation patients. Materials and Methods: A retrospective study trial including 79 patients who underwent renal transplantation. Patients were separated into two groups (catheter or without catheter). We identified 52 (65.8%) patients who received catheter wound infusion during the first 48 h postoperatively. On the other hand, 27 (34.1%) patients received standard without catheter anesthetic technique. Catheter wound infusion was achieved through a 12 cm catheter, inserted subcutaneously after abdominal closure. The catheter was placed above the external oblique aponeurosis. All postoperative data were examined to evaluate the first postoperative 48 h. This study aims to assess three variables: postoperative pain analysis through a visual analog scale, analgesics consumption, and bowel function. Results: The overall score of the three variables was studied. Regarding pain assessment, we have determined that the group of patients with catheter scored better than patients without catheter with borderline significance (66.3 vs. 61.2 consecutively; P = 0.0843). An early bowel function was noted in patients with catheters on the 2nd postoperative day (P = 0.0209). Moreover, patients without catheter consumed more painkillers with nonsignificant difference (P = 0.2499). Conclusion: Patients with catheter showed earlier bowel function than the noncatheter group on the 2nd postoperative day. The catheter group had better pain evaluation.

Peri-operative management of neuromuscular blockade: A guideline from the European Society of Anaesthesiology and Intensive Care.

Recent data indicated a high incidence of inappropriate management of neuromuscular block, with a high rate of residual paralysis and relaxant-associated postoperative complications. These data are alarming in that the available neuromuscular monitoring, as well as myorelaxants and their antagonists basically allow well tolerated management of neuromuscular blockade. In this first European Society of Anaesthesiology and Intensive Care (ESAIC) guideline on peri-operative management of neuromuscular block, we aim to present aggregated and evidence-based recommendations to assist clinicians provide best medical care and ensure patient safety. We identified three main clinical questions: Are myorelaxants necessary to facilitate tracheal intubation in adults? Does the intensity of neuromuscular blockade influence a patient's outcome in abdominal surgery? What are the strategies for the diagnosis and treatment of residual paralysis? On the basis of this, PICO (patient, intervention, comparator, outcome) questions were derived that guided a structured literature search. A stepwise approach was used to reduce the number of trials of the initial research ( n  = 24 000) to the finally relevant clinical studies ( n  = 88). GRADE methodology (Grading of Recommendations, Assessment, Development and Evaluation) was used for formulating the recommendations based on the findings of the included studies in conjunction with their methodological quality. A two-step Delphi process was used to determine the agreement of the panel members with the recommendations: R1 We recommend using a muscle relaxant to facilitate tracheal intubation (1A). R2 We recommend the use of muscle relaxants to reduce pharyngeal and/or laryngeal injury following endotracheal intubation (1C). R3 We recommend the use of a fast-acting muscle relaxant for rapid sequence induction intubation (RSII) such as succinylcholine 1 mg kg -1 or rocuronium 0.9 to 1.2 mg kg -1 (1B). R4 We recommend deepening neuromuscular blockade if surgical conditions need to be improved (1B). R5 There is insufficient evidence to recommend deep neuromuscular blockade in general to reduce postoperative pain or decrease the incidence of peri-operative complications. (2C). R6 We recommend the use of ulnar nerve stimulation and quantitative neuromuscular monitoring at the adductor pollicis muscle to exclude residual paralysis (1B). R7 We recommend using sugammadex to antagonise deep, moderate and shallow neuromuscular blockade induced by aminosteroidal agents (rocuronium, vecuronium) (1A). R8 We recommend advanced spontaneous recovery (i.e. TOF ratio >0.2) before starting neostigmine-based reversal and to continue quantitative monitoring of neuromuscular blockade until a TOF ratio of more than 0.9 has been attained. (1C).

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.

Medical disease and ambulatory surgery, new insights in patient selection based on medical disease.

PURPOSE OF REVIEW: Improvements in perioperative care contributed to enlarge the eligibility criteria for day case surgery and more and more patients with comorbidities may be concerned. However, underlying medical diseases may influence postoperative outcomes, and therefore, must be considered when selecting patients to undergo ambulatory surgery. RECENT FINDINGS: To limit postoperative complications, rigid patient selection criteria are often applied in ambulatory surgery. In practice, however, most of these criteria predict the occurrence of treatable perioperative adverse events but not the need for unanticipated admission or readmission. SUMMARY: The underlying medical diseases should not be considered as sole criteria but they should rather be regarded as a dynamic process, which includes the surgical procedure as well as the experience and expertise of the perioperative setting.

A modified TOF-ratio to assess rocuronium-induced neuromuscular block: a comparison with the usual TOF-ratio.

BACKGROUND: The TOFscan is an acceleromyographic neuromuscular monitor that calculates and displays two measurements: first, a train-of-four (TOF) ratio, or ratio of the fourth twitch in the TOF-sequence, T4, and the first twitch, T1 (T4/T1). In addition, a second, modified ratio is displayed (T4/Tr), which refers to the ratio between T4 and a reference twitch (Tr), calculated as the mean value of the four twitches in a TOF-sequence [Tr = (T1 + T2 + T3 + T4)/4]. T4/Tr is calculated before establishment of neuromuscular block. METHODS: This prospective observational study included 35 adult patients. NMB induced by a rocuronium bolus of 0.6 mg/kg was continuously monitored at the adductor pollicis with the TOFscan and both TOF-ratios were simultaneously assessed. Primary outcome was the comparison of recovery to a TOF-ratio ≥ 0.9 calculated as T4/T1 and T4/Tr. RESULTS: The first value of the T4/T1 ≥ 90% was 90.9 (1.1) % and the simultaneously calculated T4/Tr was 69.6 (9.3) %, P < 0.001. The first value of the T4/Tr ≥ 90% was 90.5 (1.1) %, the simultaneously T4/T1 was 97.3 (2.5) %, P < 0.001. Time from injection of rocuronium to a TOF-ratio ≥ 90% was 56.2 ± 17.1 min for the T4/T1 and 65.3 ± 19.3 min for the T4/Tr, P < 0.001. During onset, a TOF ratio ≤ 20% was reached 145.5 (50.5) s after rocuronium when considering T4/T1, and 114.5 (45) s with the T4/Tr, P < 0.001. CONCLUSION: The present study shows the limitations of the usually determined acceleromyographic TOF ratio (T4/T1) in determining adequate neuromuscular recovery. The T4/T1 ratio significantly overestimates recovery compared with the T4/Tr ratio. Clinical decisions of adequate neuromuscular recovery based on the new T4/Tr ratio may reduce the incidence of residual paralysis and improve patient safety.

The impact of deep versus standard neuromuscular block on intraoperative safety during laparoscopic surgery: an international multicenter randomized controlled double-blind strategy trial - EURO-RELAX TRIAL.

BACKGROUND: Muscle relaxants are routinely used during anesthesia to facilitate endotracheal intubation and to optimize surgical conditions. However, controversy remains about the required depth of neuromuscular block (NMB) needed for optimal surgical working conditions and how this relates to other outcomes. For instance, a deep neuromuscular block yields superior surgical working conditions compared to a standard NMB in laparoscopic surgery, however, a robust association to other (safety) outcomes has not yet been established. METHODS: Trial design: an international multicenter randomized controlled double-blind strategy trial. Trial population: 922 patients planned for elective, laparoscopic or robotic, abdominal surgery. INTERVENTION: Patients will be randomized to a deep NMB (post-tetanic count 1-2 twitches) or standard care (single-dose muscle relaxant administration at induction and repeated only if warranted by surgical team). Main trial endpoints: Primary endpoint is the difference in incidence of intraoperative adverse events during laparoscopic surgery graded according to ClassIntra® classification (i.e., ClassIntra® grade ≥ 2) between both groups. Secondary endpoints include the surgical working conditions, 30-day postoperative complications, and patients' quality of recovery. DISCUSSION: This trial was designed to analyze the effect of deep neuromuscular block compared to standard neuromuscular block on intra- and postoperative adverse events in patients undergoing laparoscopic surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT04124757 (EURO-RELAX); registration URL: https://clinicaltrials.gov/ct2/show/NCT04124757 , registered on October 11th, 2019.

Neuromuscular block in patients 80 years and older: a prospective, controlled study.

BACKGROUND: An increasing number of patients older than 80 years are undergoing anesthesia, but little information is available regarding pharmacodynamic effects of myorelaxants in this population. This study aims to compare the time course of rocuronium neuromuscular block in patients ≥ 80 years with those of younger adults. METHODS: Under total intravenous anesthesia with propofol and sufentanil, time course of a bolus of rocuronium 0.6 mg/kg neuromuscular block was assessed with acceleromyography in patients ≥ 80 and in patients 20-50 years old. Onset time, clinical duration, duration until 90% and 100% recovery of baseline were determined. RESULTS: Data from 32 patients were analyzed, 16 were ≥ 80 years and 16 were 20-50 years old. Demographic data are shown in Table 1. In the group ≥ 80, onset time was 190 s ± 46 s compared to 123 s ± 40 s in the group 20-50, P < 0.001 and the clinical duration was 52 [48-69.5] min and 36 [34-41] min, respectively, P < 0.001. Duration to 90% recovery of baseline was 77.5 [71-88.5] min and duration to 100% recovery of baseline was 91.2 [82.2-98] min in patients ≥ 80 years and the corresponding values in the patients 20-50 years old were 53.5 [49-55.5] min and 59.5 [56.5-70.25] min, respectively, P < 0.001. CONCLUSION: Compared to younger adults rocuronium shifted in patients ≥ 80 years from a rapid onset, intermediate acting compound to a slower onset, long-acting compound. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03551652 (29/05/2018).

Impact of rocuronium on intraoperative neuromonitoring vagal amplitudes during thyroidectomy.

PURPOSE: Neuromuscular blocking agents (NMBA) facilitate endotracheal intubation and reduce related laryngeal morbidity. However, NMBA interfere with intraoperative neuromonitoring amplitudes during thyroidectomy. The goal of this study was to evaluate the impact of rocuronium used for tracheal intubation on early intraoperative neuromonitoring vagal amplitudes observed during first thyroid lobe dissection. METHODS: This is an observational pharmacoepidemiological study with prospective data collection and retrospective analysis. During the study period, all consecutive patients who underwent thyroid surgery with neuromonitoring were included. Patients underwent endotracheal intubation either using a single dose of rocuronium (NMBA group) or without NMBA (NMBA-free group) according to the anesthesiologist's preference. RESULTS: Six hundred six patients were included (213 NMBA and 393 NMBA-free group patients). At V1, 39 patients (18%) in the NMBA group had an amplitude < 100 µV (need for curarization reversal in 30 patients) and 13 patients (3.3%) in the NMBA-free group (p < 0.001). In the remaining 554 patients, the mean V1 amplitude was significantly decreased in the NMBA group (544 versus 685 µV; p < 0.001). After exclusion of 25 patients with loss of signal types 1 and 2 during dissection, the difference between mean V1 and mean V2 was significantly lower in NMBA group patients (- 22 versus - 86 µV; p = 0.016). CONCLUSION: This study provides new data showing how NMBA used for tracheal intubation significantly decrease V1 amplitude baseline and modify amplitude variations from V1 to V2 values during the first thyroid lobe dissection. LEVEL OF EVIDENCE: Pharmacoepidemiological study.