A randomized trial evaluating the safety profile of sugammadex in high surgical risk ASA physical class 3 or 4 participants

Background The aim of this randomized, double-blind trial was to evaluate the safety and tolerability profile, including cardiac safety, of sugammadex-mediated recovery from neuromuscular block in participants undergoing surgery who met the American Society of Anesthesiologists (ASA) Physical Class 3 or 4 criteria. Specifically, this study assessed the impact of sugammadex on cardiac adverse events (AEs) and other prespecified AEs of clinical interest. Methods Participants meeting ASA Class 3 and 4 criteria were stratified by ASA Class and NMBA (rocuronium or vecuronium) then randomized to one of the following: 1) Moderate neuromuscular block, sugammadex 2 mg/kg; 2) Moderate neuromuscular block, neostigmine and glycopyrrolate (neostigmine/glycopyrrolate); 3) Deep neuromuscular block, sugammadex 4 mg/kg; 4) Deep neuromuscular block, sugammadex 16 mg/kg (rocuronium only). Primary endpoints included incidences of treatment-emergent (TE) sinus bradycardia, TE sinus tachycardia and other TE cardiac arrhythmias. Results Of 344 participants randomized, 331 received treatment (61% male, BMI 28.5 ± 5.3 kg/m2, age 69 ± 11 years). Incidence of TE sinus bradycardia was significantly lower in the sugammadex 2 mg/kg group vs neostigmine/glycopyrrolate. The incidence of TE sinus tachycardia was significantly lower in the sugammadex 2 and 4 mg/kg groups vs neostigmine/glycopyrrolate. No significant differences in other TE cardiac arrythmias were seen between sugammadex groups and neostigmine/glycopyrrolate. There were no cases of adjudicated anaphylaxis or hypersensitivity reactions in this study. Conclusions Compared with neostigmine/glycopyrrolate, incidence of TE sinus bradycardia was significantly lower with sugammadex 2 mg/kg and incidence of TE sinus tachycardia was significantly lower with sugammadex 2 mg/kg and 4 mg/kg. These results support the safety of sugammadex for reversing rocuronium- or vecuronium-induced moderate and deep neuromuscular block in ASA Class 3 or 4 participants. Trial registration ClinicalTrials.gov Identifier: NCT03346057.

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.

Efficiency and Safety of the Selective Relaxant Binding Agent Adamgammadex Sodium for Reversing Rocuronium-Induced Deep Neuromuscular Block: A Single-Center, Open-Label, Dose-Finding, and Phase IIa Study

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.

Rapid arousal from anaesthesia after reversal of deep rocuronium-induced neuromuscular block with sugammadex in a neuroradiological procedure

We describe the case of a 42-year-old man undergoing elective embolisation of an arteriovenous malformation at the level of the right posterior cerebral artery under propofol anaesthesia. We used the SedLine Brain Function Monitor (Masimo) to titrate the anaesthetic depth with propofol. At the end of the procedure, the patient aroused from anaesthesia very rapidly after the reversal of deep neuromuscular block with sugammadex, despite still significant calculated doses of propofol at the effect site. This rapid arousal was monitored using the SedLine Brain Function Monitor.

The influence of moderate or deep neuromuscular block status on anesthetic depth monitoring system during total intravenous anesthesia using propofol and remifentanil: A randomized trial

The neuromuscular block state may affect the electroencephalogram-derived index representing the anesthetic depth. We applied an Anesthetic Depth Monitoring for Sedation (ADMS) to patients undergoing laparoscopic cholecystectomy under total intravenous anesthesia, and evaluated the requirement of propofol according to the different neuromuscular block state. Adult patients scheduled to undergo laparoscopic cholecystectomy were enrolled and randomly assigned to either the moderate (MB) or deep neuromuscular block (DB) group. The UniCon sensor of ADMS was applied to monitor anesthetic depth and the unicon value was maintained between 40 and 50 during the operation. According to the group assignment, intraoperative rocuronium was administered to maintain proper neuromuscular block state, moderate or deep block state. The unicon value, electromyography (EMG) index, and total dose of propofol and rocuronium were analyzed. At similar anesthetic depth, less propofol was used in the DB group compared to the MB group (6.19 ± 1.36 in the MB mg/kg/h group vs 4.93 ± 3.02 mg/kg/h in the DM group, p = 0.042). As expected, more rocuronium were used in the DB group than in the MB group (0.8 ± 0.2 mg/kg in the MB group vs 1.2 ± 0.2 mg/kg in the DB group, p = 0.023) and the EMG indices were lower in the DB group than in the MB group, at several time points as follows: at starting operation ( p < 0.001); at 15 ( p = 0.019), 45 ( p = 0.011), and 60 min ( p < 0.001) after the initiation of the operation; at the end of operation ( p = 0.003); and at 5 min after the administration of sugammadex ( p < 0.001). At similar anesthetic depth, patients under the deep neuromuscular block state required less propofol with lower intraoperative EMG indices compared to those under the moderate neuromuscular block state during general anesthesia.

Effects of deep neuromuscular block with low-pressure pneumoperitoneum on respiratory mechanics and biotrauma in a steep Trendelenburg position

We hypothesized that deep neuromuscular blockade (NMB) with low-pressure pneumoperitoneum (PP) would improve respiratory mechanics and reduce biotrauma compared to moderate NMB with high-pressure PP in a steep Trendelenburg position. Seventy-four women undergoing robotic gynecologic surgery were randomly assigned to two equal groups. Moderate NMB group was maintained with a train of four count of 1–2 and PP at 12 mmHg. Deep NMB group was maintained with a post-tetanic count of 1–2 and PP at 8 mmHg. Inflammatory cytokines were measured at baseline, at the end of PP, and 24 h after surgery. Interleukin-6 increased significantly from baseline at the end of PP and 24 h after the surgery in moderate NMB group but not in deep NMB group (Pgroup*time = 0.036). The peak inspiratory, driving, and mean airway pressures were significantly higher in moderate NMB group than in deep NMB group at 15 min and 60 min after PP (Pgroup*time = 0.002, 0.003, and 0.048, respectively). In conclusion, deep NMB with low-pressure PP significantly suppressed the increase in interleukin-6 developed after PP, by significantly improving the respiratory mechanics compared to moderate NMB with high-pressure PP during robotic surgery.

Neuromuscular block monitoring by smartphone application (i-TOF© system): an observational pilot study

Neuromuscular block monitoring is recommended by international guidelines to improve myorelaxation during surgery and reduce the risk of postoperative residual curarization. We conducted a pilot study to verify the efficacy of i-TOF, a wireless neuromuscular monitoring device connectable to a smartphone, comparing it with TOF WATCH SX. We enrolled 53 patients who underwent general anesthesia. For each patient, we recorded by both devices, in different time intervals, train-of-four (TOF) count/ratio after induction to general anesthesia (TI0–TI3) and during recovery (TR0–TR3). Moreover, post-tetanic count (PTC) was evaluated during deep neuromuscular block (TP0–TP2). We noticed no significant differences between the devices in recorded mean values of TOF ratio, TOF count, and PTC analyzed at time intervals for every phase of general anesthesia, although the i-TOF tends to an underestimation compared to TOF WATCH SX. For each patient, data sessions were successfully recorded by a smartphone. This aspect could be relevant for clinicians in order to have a stored proof of good clinical practice to be added on anesthesiologist records. By our results, i-TOF demonstrates a comparable efficacy to TOF WATCH SX, suggesting that it could be a proven alternative to standard devices for neuromuscular block monitoring. Further studies are needed to confirm our findings.