Comparison between conventional-dose and high-dose rocuronium use in general anesthesia for Cesarean section.

Background: There have been few studies comparing the effects of high- and low-dose rocuronium during cesarean section by directly measuring the concentration. Therefore, we conducted a study to examine the blood concentrations and clinical effects of both doses of rocuronium on mothers and fetuses. Methods: Eighteen patients were randomly assigned to two groups: C Group (0.6 mg/kg), and H Group, (1.0 mg/kg). The primary outcome was the comparison of umbilical vein rocuronium concentration between two groups. We assessed ease of intubation, time from rocuronium administration to some TOF points, post-anesthesia care unit (PACU) stay time, infused remifentanil dose, maternal rocuronium concentration, and Apgar scores. Results: No differences were observed in demographic data, ease of intubation, PACU stay time, 1 min Apgar scores, umbilical venous blood gas analysis between both groups. However, the time from rocuronium administration to T3 disappearance was shorter (p=0.009) and time to T1 and T2 reappearance were longer (p=0.003, p=0.009) in H group than that in C group. The administered remifentanil dose (p=0.042) was lower in the H group than in the C group. Rocuronium concentrations in the umbilical vein (p=0.004) and maternal vein before cord clamping (p=0.002) and at discharge (p<0.001) were also found to be higher in the H group than in the C group. Conclusions: We observed no prolongation of PACU stay, and no differences in Apgar scores in H group compared to C group. It suggests that 1.0 mg/kg of rocuronium has no negative effects on the fetus and mother in cesarean section.

Comparing Neuromuscular Blockade Measurement Between Upper Arm (TOF Cuff®) and Eyelid (TOF Scan®) Using Mivacurium during General Anesthesia.

BACKGROUND Mivacurium is a non-depolarizing neuromuscular blocking agent. TOF-Cuff® is a device that monitors intraoperative neuromuscular blockade and blood pressure. TOF-Scan® measures muscle relaxation status of an anaesthetized patient. This study included 36 patients aged 18 to 75 years presenting for elective surgery, to compare neuromuscular blockade measured using the TOF-Cuff of the upper arm and the TOF-Scan of the facial corrugator supercilii muscle during general anesthesia and following administration of mivacurium. MATERIAL AND METHODS Train-of-four (TOF) values were obtained every 30 s before intubation and successively every 5 min until extubation. RESULTS The median onset time for TOF-Cuff was longer than for TOF-Scan (210 s vs 90 s, P<0.00001). Multiplying the time to relaxation (according to TOF-Scan) by 1 to 8, respectively, provided concordance with the TOF-Cuff result for the following cumulative percentages of patients: 5.5%, 38.9%, 58.3%, 77.8%, 83.3%, 86.1%, 88.9%, and 91.7%. Analogue values for time to recovery from the last dose were 11.1%, 63.9%, 83.3%, 86.1%, 86.1%, 88.9%, 88.9%, and 91.7%. The proportion of patients who still had TOFratio=0 in the assessment performed at min 15 did not differ significantly between these 2 methods (P=0.088). Both TOF-Scan and TOF-Cuff showed a false-negative result in patients with clinical symptoms of preterm recovery; the numerical difference favored TOF-Cuff (1.6% vs 2.1%) but without statistical significance (P=0.2235). CONCLUSIONS When measurement on the limb is not possible, TOF-Scan on the eyelid can be an alternative for TOF-Cuff on the upper arm, if the time to relaxation is multiplied by at least 8, which is enough for 90% of patients.

Comparison of rocuronium priming vs. standard rapid sequence intubation technique in emergency department patients requiring intubation.

OBJECTIVE: In our study, we aimed to compare the effect of standard rapid sequence intubation protocol and the application of rocuronium priming technique on the procedure time and hemodynamic profile. METHODS: Patients who applied to the emergency department and needed rapid sequence intubation were included in our study, which we conducted with a randomized controlled design. Randomization in the study was made according to the order of arrival of the cases. Rapid sequence intubation was performed in the standard group. In the priming group, 10% of the rocuronium dose was administered approximately 3 min before the induction agent. Intubation time, amount of drug used, vital signs, and end-tidal CO2 level before and after intubation used to confirm intubation were recorded. RESULTS: A total of 52 patients were included in the study, of which 26 patients were included in the standard group and 26 patients in the priming group. While intubation time was 121.2±21.9 s in the standard group, it was calculated as 68.4±11.6 s in the priming group (p<0.001). While the mean arterial pressure was 58.3±26.6 mmHg in the standard group after intubation, it was 80.6±21.1 mmHg in the priming group (p=0.002). CONCLUSION: It was observed that priming with rocuronium shortened the intubation time and preserved the hemodynamic profile better. CLINICAL TRIAL REGISTRATION NUMBER: NCT05343702.

A compressomyograph train of four monitoring device.

The monitoring of the neuromuscular blockade is critical for patient's safety during and after surgery. The monitoring of neuromuscular blockade often requires the use of Train of Four (TOF) technique. During a TOF test two electrodes are attached to the ulnar nerve, and a series of four electric pulses are applied. The electrical stimulation causes the thumb to twitch, and the amount of twitch varies depending on the amount of neuromuscular blockade in patient's system. Current medical devices used to assist anesthesiologists to perform TOF monitoring often require free hand movement and do not provide accurate or reliable results. The goal of this work is to design, prototype and test a new medical device that provides reliable TOF results when thumb movement is restricted. A medical device that uses a pressurized catheter balloon to detect the response thumb twitch of the TOF test is created. An analytical model, numerical study, and mechanical finger testing were employed to create an optimum design. The design is tested through a pilot human subjects study. No significant correlation is reported with subjects' properties, including hand size.

Unraveling the molecular dynamics of sugammadex-rocuronium complexation: A blueprint for cyclodextrin drug design.

Sugammadex, marketed as Bridion™, is an approved cyclodextrin (CD) based drug for the reversal of neuromuscular blockade in adults undergoing surgery. Sugammadex forms an inclusion complex with the neuromuscular blocking agent (NMBA) rocuronium, allowing rapid reversal of muscle paralysis. In silico methods have been developed for studying CD inclusion complexes, aimed at accurately predicting their structural, energetic, dynamic, and kinetic properties, as well as binding constants. Here, a computational study aimed at characterizing the sugammadex-rocuronium system from the perspective of docking calculations, free molecular dynamics (MD) simulations, and biased metadynamics simulations with potential of mean force (PMF) calculations is presented. The aim is to provide detailed information about this system, as well as to use it as a model system for validation of the methods. This method predicts results in line with experimental evidence for both the optimal structure and the quantitative value for the binding constant. Interestingly, there is a less profound preference for the orientation than might be assumed based on electrostatic interactions, suggesting that both orientations may exist in solution. These results show that this technology can efficiently analyze CD inclusion complexes and could be used to facilitate the development and optimization of novel applications for CDs.

Comparison of Deep and Moderate Neuromuscular Blockade for Major Laparoscopic Surgery in Children: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Neuromuscular blocking agents are routinely used in laparoscopic surgery to optimize operative conditions. We compared the effect of a deep and moderate neuromuscular blockade (NMB) on surgical conditions and postoperative outcomes in children undergoing major laparoscopic surgery. METHODS: Sixty children aged 2-14 years scheduled to undergo major laparoscopic surgery were randomly allocated to deep (post-tetanic count 1-2 twitches) or moderate (train-of-four 1-2 twitches) NMB groups. The anesthesia was maintained with propofol and remifentanil, and the NMB was maintained with a rocuronium continuous infusion. At the end of the operation, the NMB were antagonized with sugammadex. The intra-abdominal pressure, airway pressure, Leiden Surgical Rating Scale, intraoperative hemodynamics, drug usages, duration of surgery, postoperative recovery time, pain, and complications were compared between the groups. RESULTS: The maximum and mean intra-abdominal pressure, the peak inspiratory pressure, and mean airway pressure were significantly lower in the deep NMB group than in the moderate NMB group (p < 0.001). The Leiden Surgical Rating Scale and the dosage of rocuronium were significantly higher in the deep NMB group than the moderate NMB group (p < 0.001). The intraoperative hemodynamics, duration of surgery, post-operative recovery time, pain, and the incidence rate of complications were not significantly different between the groups (p > 0.05). CONCLUSIONS: A deep NMB provided better operative conditions and similar recovery profiles compared with a moderate NMB as reversed with sugammadex in children undergoing major laparoscopic surgery. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry, No. ChiCTR2100053821.

Pillar[6]MaxQ functions as an in vivo sequestrant for rocuronium and vecuronium.

The binding affinity of pillar[6]MaxQ toward a panel of neuromuscular blockers and neurotransmitters was measured in phosphate buffered saline by isothermal titration calorimetry and 1H NMR spectroscopy. In vivo efficacy studies showed that P6MQ sequesters rocuronium and vecuronium and reverses their influence on the recovery of the train-of-four (TOF) ratio.

Trapping and reversing neuromuscular blocking agent by anionic pillar[5]arenes: Understanding the structure-affinity-reversal effects.

Selective relaxant binding agents (SRBA) have great potential in clinical surgeries for the precise reversal of neuromuscular blockades. Understanding the relationship between the structure-affinity-reversal effects of SRBA and neuromuscular blockade is crucial for the design of new SRBAs, which has rarely been explored. Seven anionic pillar[5]arenes (AP5As) with different aliphatic chains and anionic groups at both edges were designed. Their binding affinities to the neuromuscular blocking agent decamonium bromide (DMBr) were investigated using 1H NMR, isothermal titration calorimetry (ITC), and theoretical calculations. The results indicate that the capture of DMBr by AP5As is primarily driven by electrostatic interactions, ion-dipole interactions and C-H‧‧‧π interactions. The optimal size matching between the carboxylate AP5As and DMBr was ∼0.80. The binding affinity increased with an increase in the charge quantity of AP5As. Further animal experiments indicated that the reversal efficiency increased with increasing binding affinity for carboxylate or phosphonate AP5As. However, phosphonate AP5As exhibited lower reversal efficiencies than carboxylate AP5As, despite having stronger affinities with DMBr. By understanding the structure-affinity-reversal relationships, this study provides valuable insights into the design of innovative SRBAs for reversing neuromuscular blockade.

Sugammadex shortens operation time and improves operation turnover efficacy in video-assisted thoracoscopic surgery.

BACKGROUND: This study compared sugammadex and neostigmine as agents for routine neuromuscular blockade reversal in video-assisted thoracoscopic surgery (VATS) to determine the optimal choice that achieves a shorter operation time and improved turnover efficiency while enhancing postoperative outcomes and ensuring patient safety during thoracic surgery. METHODS: This prospective study, conducted from July 2022 to March 2023, compared the effect of sugammadex and neostigmine on operation time and turnover efficiency in VATS, involving 60 participants randomly assigned to either group, with the primary objective of identifying the optimal anesthesia reversal choice for improved outcomes and patient safety during thoracic surgery. RESULTS: In the study, the sugammadex group showed a significantly shorter total operation room occupancy time (130 ± 7 vs 157 ± 7 minutes; p = 0.009) than the neostigmine group. Patients in the neostigmine group had higher mean pulse rates when leaving the operation room (85 ± 3 vs 73 ± 3 beats/min; p = 0.002) and 120 minutes later in the postanesthesia care unit (76 ± 2 vs 68 ± 2; p = 0.016). CONCLUSION: This study's findings suggest that sugammadex may enhance total operating room occupancy time, operation turnover efficacy, and respiratory recovery outcomes in VATS, potentially improving patient care and anesthesia management.

Effects of a single dose of rocuronium in patients with different body fat percentages: A randomised controlled trial.

The pharmacodynamics in patients with high body fat percentage might be similar to those in obese patients. This randomised controlled clinical trial observed the effects of rocuronium in patients with different percent body fats (PBFs). Fifty-four patients who underwent elective urological or pelvic surgery under general anaesthesia at Shanghai General Hospital were included in the present study; 51 patients were included for data analysis. Patients with normal PBF (<25%) were given a single dose of rocuronium calculated based on total body weight (N-TBW, control group). Patients with a higher PBF (≥25%) were given a single dose of rocuronium calculated based on total body weight (H-TBW). Patients with higher PBF and rocuronium were dosed based on fat-free mass (H-FFM). A train of four (TOF)-Watch acceleromyography monitor was used to measure the effects of the rocuronium. H-TBW (91.9 ± 28.8 s) had significantly shorter onset time than N-TBW and H-FFM (p = 0.003). H-TBW had significantly longer clinical duration time and pharmacological duration time than the other groups (p = 0.000 and 0.000, respectively); the TOF ratio0.25-0.9 time was significantly different among the three groups (p = 0.005). There were no significant differences in the recovery time (p = 0.103) or recovery index (p = 0.159) among the three groups. The effects of rocuronium dosed based on FFM in patients with high PBFs are similar to those in normal patients. A single dose of rocuronium calculated based on TBW might shorten the onset time, prolong the clinical and pharmacological duration times, and prolong the recovery time.

Sugammadex Versus Neostigmine for Reversal of Neuromuscular Blockade in Patients With Severe Renal Impairment: A Randomized, Double-Blinded Study.

BACKGROUND: Sugammadex is not advised for patients with severe renal impairment, but has been shown in a variety of other populations to be superior to neostigmine for reversal of neuromuscular blockade. The objective of this study was to determine if reversal of rocuronium-induced neuromuscular blockade with sugammadex versus reversal of cisatracurium-induced neuromuscular blockade with neostigmine results in a faster return to a train-of-four ratio (TOFR) ≥90% in patients with severe renal impairment. METHODS: We conducted a prospective, randomized, blinded, controlled trial at a large county hospital. A total of 49 patients were enrolled. Inclusion criteria included patients age ≥18, American Society of Anesthesiologists (ASA) physical status III and IV, with a creatinine clearance <30 mL/min, undergoing general anesthesia with expected surgical duration ≥2 hours and necessitating neuromuscular blockade. Subjects received either cisatracurium 0.2 mg/kg or rocuronium 0.6 mg/kg for induction of anesthesia to facilitate tracheal intubation. Subjects were kept at moderate neuromuscular blockade during surgery and received either 2 mg/kg sugammadex or 50 µg/kg neostigmine with 10 µg/kg glycopyrrolate for reversal of neuromuscular blockade. Neuromuscular monitoring was performed with electromyography (TwitchView), and the TOFR was recorded every minute after administration of the reversal agent. The time from administration of neuromuscular reversal until the patient reached a TOFR ≥90% was recorded as the primary outcome. RESULTS: The mean time to recovery of TOFR ≥90% was significantly faster with sugammadex at 3.5 (±1.6) min compared with neostigmine at 14.8 (±6.1) min ( P < .0001; mean difference, 11.3 minutes; 95% confidence interval [CI], 9.0-13.5 minutes). There were no major adverse events in either group. CONCLUSIONS: In patients with severe renal impairment, neuromuscular blockade with rocuronium followed by reversal with sugammadex provides a significantly faster return of neuromuscular function compared to cisatracurium and neostigmine, without any major adverse effects.

Rocuronium Dosing by Ideal vs Total Body Weight in Obesity: A Prospective, Observational Non-inferiority Study.

Background: Providing adequate paralysis and appropriate sedation is challenging in patients with obesity during rapid sequence intubation (RSI). Pharmacokinetic parameters play an important role in dosing of rocuronium due to low lipophilicity. Rocuronium may be dosed based on ideal body weight (IBW). Current guidelines do not offer recommendations for dosing in the setting of obesity. Dosing depends on clinician preference based on total body weight (TBW) or IBW. Objective: In this study we performed non-inferiority analysis to compare the intubation conditions, duration of paralysis, and incidence of new-onset tachycardia or hypertension after intubation in obese patients requiring RSI in the emergency department (ED). Methods: This was a single-center, prospective, observational study. Eligible for enrollment were adult patients with a TBW ≥30% IBW or body mass index ≥30 kilograms per meters squared who presented to the ED requiring RSI with the use of rocuronium. Rocuronium was dosed according to intubating physicians' preference. Physicians completed a survey assessing intubation conditions. Height and weight used for the calculation of the dose, the dose of rocuronium, time of administration, and time of muscle function recovery were recorded. Endpoints assessed included grading of view during laryngoscopy, first-past success, and duration of paralysis. Results: In total, 96 patients were included, 54 in TBW and 42 in IBW. The TBW cohort received a mean of 1 milligram per kilogram (mg/kg) compared to 0.71 mg/kg in the IBW group. Excellent intubation conditions were observed in 68.5% in the TBW group and 73.8% in the IBW group. The non-inferiority analysis for relative risk of excellent intubation was 1.12 (P = 0.12, [90% CI 0.80-1.50]). Conclusion: Non-inferiority analysis suggests that IBW dosing provides similar optimal intubation conditions when compared to TBW dosing, but the noninferiority comparison did not reach statistical significance. This study was unable to show statistical non-inferiority for IBW dosing.

Is adamgammadex the brother of sugammadex or the next generation of reversal agent?

Sugammadex is now in widespread use to reverse the neuromuscular blocking effects of rocuronium. Adverse effects from sugammadex are rare, but anaphylactic and cardiovascular reactions to the drug have been reported. In an attempt to reduce such side-effects, a modified gamma-cyclodextrin, adamgammadex, has been developed. Phase 3 clinical trials suggest that it is slightly less potent than sugammadex and has a non-inferior speed of onset. In a multicentre trial of 310 patients, there was a suggestion of a lower incidence of allergic responses and recurarisation after adamgammadex compared with sugammadex. The clinical implications of this study are discussed in this editorial.

Sugammadex for reversal of moderate-to-deep rocuronium block in a clinical setting: A retrospective report of 10 dogs.

OBJECTIVE: To compare recovery times of sugammadex with spontaneous recovery from rocuronium-induced neuromuscular block (NMB) in dogs. STUDY DESIGN: Retrospective, unmatchedcase-control study. ANIMALS: A total of 10 dogs administered sugammadex and 10 dogs recovering spontaneously from rocuronium-induced NMB. METHODS: Files of dogs administered rocuronium between March and August 2023 were inspected. The train-of-four (TOF) count at the time of sugammadex administration and the time between administration and TOF ratio >90% (recovery time) were recorded. The recovery time for those not administered reversal agents was considered from the first TOF value >0 until TOF ratio >90%. The dose of sugammadex and the cumulative dose of rocuronium were recorded. Rocuronium doses and recovery times were compared using Mann-Whitney tests. The coefficient of determination (R2) between the cumulative rocuronium dose and sugammadex dose and the recovery time were calculated. RESULTS: Dogs in the sugammadex and spontaneous recovery groups were administered intravenously (IV) 0.76 (0.4-2.6) and 0.61 (0.3-2.9) mg kg-1 of rocuronium, respectively (p = 0.325). Recovery time after 3.9 (2.9-5.5) mg kg-1 of sugammadex IV was 1 (1-3) minutes and was 20 (10-35) min for spontaneous recovery (p < 0.0001). The R2 for rocuronium and sugammadex doses and recovery times were 0.19 (p = 0.2) and 0.012 (p = 0.758). CONCLUSIONS AND CLINICAL RELEVANCE: Sugammadex 2.9-5.5 mg kg-1 reversed moderate (TOF count 1-3) or deep (TOF count 0) rocuronium-induced NMB within 3 minutes, substantially faster than spontaneous recovery.

Sugammadex and urinary retention after hysterectomy: A propensity-matched cohort study.

Postoperative urinary retention (POUR) is a well-known complication after gynecologic surgery. Our objective was to investigate whether the choice of pharmacologic agent for reversing neuromuscular blockade at the end of a hysterectomy is a risk factor for POUR. Among adult patients undergoing hysterectomy with general anesthesia from 2012 to 2017, those who received aminosteroid nondepolarizing neuromuscular agents followed by pharmacologic reversal were identified, and electronic health records were reviewed. The cohort was dichotomized into two groups by reversal agent: 1) sugammadex and 2) neostigmine with glycopyrrolate. The primary outcome, POUR, was defined as unplanned postoperative bladder recatheterization. A propensity-adjusted analysis was performed to investigate the association between POUR and reversal agent by using inverse probability of treatment weighting to adjust for potential confounders. We identified 1,974 patients, of whom 1,586 (80.3%) received neostigmine-glycopyrrolate and 388 (19.7%) received sugammadex for reversal of neuromuscular blockade. The frequency of POUR was 24.8% (393/1,586) after reversal with neostigmine-glycopyrrolate and 18.3% (71/388) with sugammadex. Results from the propensity-adjusted analysis showed that sugammadex was associated with a lower POUR risk than neostigmine-glycopyrrolate (odds ratio 0.53, 95% confidence interval [CI] 0.37 - 0.76, P < 0.001). A post hoc analysis of sugammadex recipients who received glycopyrrolate for another indication showed a higher POUR risk than among those who did not receive glycopyrrolate (odds ratio 1.86, 95% CI 1.07 - 3.22, P = 0.03). Use of sugammadex to reverse aminosteroid neuromuscular blocking agents is associated with decreased risk of POUR after hysterectomy. A potential mechanism is the omission of glycopyrrolate, which is coadministered with neostigmine to mitigate unwanted cholinergic effects.