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Background: Sugammadex rapidly reverses the nondepolarizing neuromuscular blocking agents (NMBAs) rocuronium and vecuronium. The role of sugammadex is not well-defined outside of the postoperative setting., Objective: This study aims to describe sugammadex use outside the postoperative setting for the reversal of nondepolarizing NMBAs., Methods: This was a single-center, retrospective cohort study conducted in patients who received sugammadex outside of the postoperative setting at an academic medical center between June 2016 and November 2022. The primary outcome was the effect of sugammadex use for rocuronium reversal, defined as any increase in train-of-four (TOF) after sugammadex administration and/or progress note documentation if TOF was unavailable. Secondary outcomes included adverse events and documentation of contraceptive counseling in patients taking hormonal contraceptives with child-bearing ability., Results: A total of 14 383 patients received sugammadex during the study period. Of those patients, 39 (0.3%) were outside of the postoperative setting for the reversal of rocuronium and included in the study. Twenty-nine (74%) patients had an increase in TOF after sugammadex administration and/or progress note documentation if TOF was unavailable. Ten (26%) patients lacked documentation regarding the effect of sugammadex. No adverse reactions were reported. Three (8%) patients included in the study were of child-bearing ability, and 1 of the 3 patients was counseled on using an alternative method of contraception following sugammadex administration., Conclusion and Relevance: There is a paucity of literature for the use of sugammadex outside of the postoperative setting. This study found that while the use of sugammadex was rare, overall, it was safe and well-tolerated., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Objective: To compare the effects of neostigmine/glycopyrrolate (a traditional agent) and sugammadex on bowel motility recovery and the occurrence of digestive system complications after colorectal surgery., Design: Prospective, randomized controlled trial., Setting: A single tertiary center., Patients: 111 patients undergoing laparoscopic colorectal surgery., Interventions: Patients were randomized into two groups based on the block reversal agent: 1) a mixture of 50 μg.kg -1 of neostigmine and 10 μg.kg-1 of glycopyrrolate (neostigmine group) and 2) 2 mg.kg -1 of sugammadex (sugammadex group)., Measurements: The primary outcome was the time from the surgery's completion to the first flatus. The time to the first postoperative defecation, incidences of postoperative nausea or vomiting, ileus, and dry mouth, as well as postoperative length of stay, were also assessed., Main Results: The time to the first flatus was significantly shorter in the sugammadex group than in the neostigmine group (59 [42-79] h vs 69 [53-90] h, P = 0.027). The time to the first defecation and the incidences of postoperative nausea or vomiting and ileus did not differ between the groups, nor did the postoperative length of stay. However, the incidence of postoperative dry mouth was significantly lower in the sugammadex group than in the neostigmine group (7 patients [13%] vs 39 patients [71%], P < 0.001)., Conclusions: The time to the first flatus was shorter using 2 mg.kg -1 sugammadex to reverse the neuromuscular block for laparoscopic colorectal surgery compared to reversal with conventional neostigmine/glycopyrrolate., Competing Interests: Declaration of competing interest No competing interests declared., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Neuromuscular blocking agents are used commonly to induce skeletal muscle relaxation during surgery. While muscle relaxation facilitates surgical procedures and tracheal intubation, adequate recovery of muscle function after surgery is required to support pulmonary function, and even mild residual neuromuscular block increases the risk of severe postoperative pulmonary complications. While recovery of muscle function after surgery involving neuromuscular blocking agents can be monitored and, in addition, be accelerated by use of current antagonists (reversal agents), there is a clear clinical need for a safe drug to antagonize all types of neuromuscular blocking agents. Here, we show that inhibition of the skeletal muscle-specific chloride ion (Cl - ) channel, the ClC-1 channel, markedly accelerates recovery of both single contraction (twitch) and, important physiologically, sustained (tetanic) contractions in a rat model mimicking neuromuscular blocking agent-induced muscle block used during surgery. This suggests ClC-1 inhibition as a mechanism for fast and efficacious recovery of neuromuscular function induced by any neuromuscular blocking agents., (© 2024. The Author(s).)

BACKGROUND To evaluate neuromuscular monitoring during anesthesia with mivacurium, this study assessed the correlation between measurements of TOF-Cuff® placed on the lower leg and stimulating the tibial nerve and TOF-Scan® values from the adductor pollicis muscle. Additionally, systolic (SBP) and diastolic (DBO) blood pressure measured in both locations were compared. MATERIAL AND METHODS Twenty-six patients participated in this observational clinical trial. The TOF-Cuff® was placed on the lower leg and the TOF-Scan® was placed on the thumb. Train-of-four (TOF) values were recorded simultaneously by both devices at 30-second intervals before intubation. Measurements continued every 5 minutes until extubation. Bland-Altman analyses compared TOF values obtained from the 2 devices. RESULTS Time to onset and relaxation time did not differ significantly; the number of patients presenting a lack of blockade despite TOF=0 was also concordant. The time from the last dose of mivacurium to TOF ratio >90 was shorter on the leg than on hand (median 20 [5-28, 0-65] min vs 30 [20-35, 0-60] min, p=0.025). The median (range, interquartile range) difference between measurements was: 11.6 (-41 to 45, 2-19) for SBP and -8 (-28 to 26, -15 to -4) for DBP at baseline (p=0.0495); 5 (-53 to 55, -2 to 9) for SBP and -11 (-45 to 29, -19 to -5) (p=0.0017) for DBP during the blockade. CONCLUSIONS Time-to-onset and SBP are comparable between these 2 methods, in contrast to time-to-recovery and diastolic blood pressure, and this should be considered in case of the inability to apply the TOF-Cuff on the leg.

Objective: To compare sugammadex with neostigmine / atropine combination for reversal of neuromuscular blocker agents in terms of postoperative gastrointestinal motility in patients who underwent laparoscopic cholecystectomy., Study Design: Experimental study. Place and Duration of the Study: University of Health Sciences, Izmir Bozyaka Training and Research Hospital, Izmir, Turkiye, between December 2020 and June 2021., Methodology: Seventy-two patients undergoing laparoscopic cholecystectomy were included. At the end of the surgery, patients were antagonised for neuromuscular blockers either by atropine / neostigmine or sugammadex by an anaesthesiologist who was not involved in the study. Total anaesthesia time, pneumoperitoneum time, surgery time, number of postoperative opioid dose requirements and total opioid dose administered, number of medication requirements for postoperative nausea and vomiting, postoperative hospital stay, and first gas and stool output time of all the cases were evaluated by the researcher who was unaware of the medicines used for antagonisation., Results: There were no statistically significant differences between the two groups in terms of their effects on postoperative gastrointestinal motility (first gas and stool output time), duration of anaesthesia, duration of surgery, duration of pneumoperitoneum, the number of postoperative opioid dose requirements, the number of drug requirements for postoperative nausea / vomiting, and the postoperative hospitalisation duration of the cases., Conclusion: Effects of reversal agents on postoperative gastrointestinal motility are still debated. Studies on this subject in the literature are both limited in number and have been conducted with different medicine combinations in a wide variety of patient populations. The authors thought that further prospective randomised studies are needed to interpret this effect more clearly., Key Words: Sugammadex, Neostigmine / atropine, Gastrointestinal motility, Laparoscopic cholecystectomy.

Background: Neuromuscular blocking agents (NMBAs) are a crucial component of anesthesia and intensive care through the relaxation of skeletal muscles. They can lead to adverse reactions such as postoperative residual neuromuscular block. Only one agent is capable of an instant block reversal in deep block situations, but is restricted to aminosteroid agents. Among animal models, non-human primates are an essential model for a great diversity of human disease models. The main objective of this study was to establish a model for NMBA monitoring with current available drugs before testing new reversal agents., Methods: Seven healthy male cynomolgus macaques were randomly assigned to this study. Experiments using macaques were approved by the local ethical committee (CEtEA #44). All animals were anesthetized according to institutional guidelines, with ketamine and medetomidine, allowing IV line placement and tracheal intubation. Anesthesia was maintained with isoflurane. Either rocuronium bromine (with or without sugammadex reversal) or atracurium besylate was evaluated. Monitoring was performed with two devices, TOF-Watch and ToFscan, measuring the T4/T1 and the T4/Tref ratios, respectively. Nonparametric Mann-Whitney statistical analyses were done when indicated., Results: NMBA monitoring required adaptation compared to humans, such as stimulus intensity and electrode placement, to be efficient and valid in cynomolgus macaques. When administered, both NMBAs induced deep and persistent neuro-muscular block at equivalent doses to clinical doses in humans. The rocuronium-induced profound neuromuscular block could be reversed using the cyclodextrin sugammadex as a reversal agent. We report no adverse effects in these models by clinical observation, blood chemistry, or complete blood count., Conclusion: These results support the use of non-human primate models for neuromuscular block monitoring. This represented the first step before the forthcoming testing of new NMBA-reversal agents., (© 2024 The Author(s). Journal of Medical Primatology published by John Wiley & Sons Ltd.)

Background: Sugammadex, a selective steroidal neuromuscular blocking agent reversal agent, is increasingly employed for the rapid restoration of neuromuscular function. This study aimed to conduct a comprehensive evaluation of sugammadex's safety profile., Methods: Adverse events (AEs) related to sugammadex reported in the FDA Adverse Event Reporting System (FAERS) database from January 2009 to September 2023 were extracted. Disproportionality analysis with four measures: reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) were employed to detect significant AEs. We also inspected for unexpected AEs absent from the sugammadex FDA approval documentation and categorized AEs based on the latest version (26.1) of 'Important Medical Event Terms List (IME list)' developed by the EudraVigilance Expert Working Group., Results: A total of 1452 reports were linked to sugammadex. At the preferred terms (PTs) levels, 98 sugammadex-related AEs were identified, including "anaphylactic reaction", "bradycardia", "bronchospasm" and "cardiac arrest". Among them, 37 representing unexpected events were absent from official FDA labeling, and 50 AEs were recognized as IME warranting observation. Notably, 19 PTs denoted serious AEs were absent from labeling yet needing IME surveillance, including: "Kounis syndrome", "angioedema", "pulseless electrical activity" and "laryngeal edema"., Conclusion: The study identified unexpected and potentially life-threatening AEs associated with sugammadex, a valuable agent for rapidly reversing neuromuscular blockade. Clinicians are advised to be mindful of these potential risks, particularly in patients with allergies or existing cardiovascular or respiratory conditions., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests. This work was supported by the National Natural Science Foundation of China (No.82301389) and the “Three million for Three Years” Project of the Academic Backbone of Shenshan Medical Center, Sun Yat-Sen Memorial Hospital (No.1303000002)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective:  Bronchopulmonary dysplasia (BPD) is the most common late morbidity for premature infants. Continuous neuromuscular blockade (CNMB) is suggested for the most unstable phase of BPD, despite no outcome data. We explored the association between duration of CNMB for severe BPD and mortality., Design:  Medical record review of children <5 years old admitted from 2016 to 2022 with BPD and one or more course of CNMB for ≥14 days., Results:  Twelve children received a total of 20 episodes of CNMB for ≥14 days (range 14-173 d) during their hospitalization. Most (10/12) were born at <28 weeks' gestation and most (11/12) with birth weight <1,000 g; 7/12 were of Black race/ethnicity. All were hospitalized since birth. Most (10/12) were initially transferred from an outside neonatal intensive care unit (ICU), typically after a >60-day hospitalization (9/12). Half (6/12) of them had a ≥60-day stay in our neonatal ICU before transferring to our pediatric ICU for, generally, ≥90 days (8/12). The primary study outcome was survival to discharge: 2/12 survived. Both had shorter courses of CNMB (19 and 25 d); only one child who died had a course ≤25 days. Just two infants had increasing length Z-scores during hospitalization; only one infant had a final length Z-score > - 2., Conclusion:  In this case series of infants with severe BPD, there were no survivors among those receiving ≥25 days of CNMB. Linear growth, an essential growth parameter for infants with BPD, decreased in most patients. These data do not support the use of ≥25 days of CNMB to prevent mortality in infants with severe BPD., Key Points: · This is a case series of neuromuscular blockade for severe BPD.. · Neuromuscular blockade did not improve linear growth.. · Ten out of 12 infants who were on prolonged neuromuscular blockade died.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: Early neuromuscular blockade with cisatracurium has been associated with improved outcomes in moderate-severe acute respiratory distress syndrome (ARDS). Previous studies have demonstrated increased drug utilization without benefits in oxygenation using fixed dose cisatracurium compared to train-of-four (TOF) titration. Objective: We sought to compare a novel, lower fixed dose cisatracurium protocol to TOF titration evaluating the impact on PaO2:FiO2 ratio (P/F). Methods: We conducted a single-center retrospective cohort study comparing fixed dose cisatracurium to TOF titration. We included patients aged 18-89 treated for COVID-19 ARDS with a baseline P/F≤200 who received a cisatracurium infusion for ≥12 h. The primary outcome was change in P/F at 48 h from baseline. Secondary outcomes included change in P/F at 24 h and 7 days, need for mechanical ventilation at day 28, and cisatracurium utilization. Results: Analyses included 125 patients (fixed dose = 65, TOF = 60). Severe ARDS was common with a baseline median P/F of 73.7 vs 79.5, P = .133. The change in P/F at 48 h was larger in the TOF cohort in the adjusted analysis (24.9 vs 70.8, P < .005). The rate and total cumulative dose of cisatracurium were higher in the fixed dose cohort (5 vs 3 mcg/kg/min, P < .001; 1034 vs 612 mg, P < .001) despite similar infusion durations (44.1 h vs 48.5 h, P = .642). Conclusions: Patients in the TOF cisatracurium cohort had improved P/F at 48 h compared to the fixed dose cohort, while also using only 60% of the cumulative dose. Future directions should include analysis of the implications of increased cisatracurium exposure on patient outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Efficacy and safety of sugammadex for the reversal of neuromuscular blocking agents (NMBAs) in patients with neuromuscular diseases remains unclear. We summarised the available evidence and evaluated the quality of data reporting and the validity of published reports., Methods: We searched for reports (any design) on the usage of sugammadex (any regimen) for the reversal of an NMBA in patients (any age) with any neuromuscular disease. We used a modified CARE checklist (maximum score 23) to assess the quality of data reporting and an original specific validity checklist (maximum score 41) that was developed through a Delphi process., Results: We retrieved 126 observational reports (386 patients). Most dealt with myasthenia gravis patients receiving rocuronium. The train-of-four ratio returned to ≥0.9 in 258 of 265 (97.4%) patients in whom neuromonitoring was used. Adverse events occurred in 14 of 332 (4.2%) patients in whom adverse events were reported as present or absent. In 90 case reports, the median score of the 23-point CARE checklist was 13.5 (inter-quartile range [IQR] 11-16). In all 126 reports, the median score of the 41-point validity checklist was 23 (IQR 20-27). Scores were positively correlated., Conclusions: These uncontrolled observations (of mainly low to moderate quality and validity) do not allow confident assessment of the efficacy and safety of sugammadex for the reversal of NMBAs in patients with neuromuscular diseases. Reporting of observational data should follow established guidelines, include specific information to ensure validity, and emphasise what the new data add to current knowledge., Systematic Review Protocol: PROSPERO 2019 (CRD42019119924)., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Purpose: Neuromuscular blocking agents (NMBAs) are commonly used during surgery, and restoring neuromuscular function at the end of surgery is vital in preventing complications of residual paralysis. Recent guidelines from the American Society of Anesthesiology recommend using sugammadex over neostigmine; however, sugammadex is significantly more expensive than neostigmine and may increase drug expenditure for pharmacy departments. This review summarizes evidence evaluating sugammadex dose adjustments and the potential of these dose adjustments to lead to cost savings for pharmacy departments., Summary: We found evidence suggesting that the manufacturer-recommended sugammadex dose may not be needed in many patients and that dosing based on an adjusted body weight or based on depth of neuromuscular blockade may lead to lower sugammadex usage. Combining sugammadex with neostigmine could also decrease the dose of sugammadex required. We have highlighted the importance of objective neuromuscular monitoring to guide sugammadex dosing and evaluation for residual neuromuscular blockade. Cost savings for pharmacy departments may be realized by these alternative dosing strategies and/or vial-splitting practices., Conclusion: Implementing practices related to sugammadex vial splitting and dose adjustment based on body weight and depth of neuromuscular blockade shows potential benefits in terms of sugammadex cost savings., (© American Society of Health-System Pharmacists 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Early recovery of neuromuscular and bowel function after abdominal surgery are important clinical indicators of postoperative recovery. This study aimed to investigate the effects of sugammadex, and neostigmine added to sugammadex, on postoperative bowel function and recovery from neuromuscular blocking agents., Methods: Ninety gynecological surgery patients, aged 18 to 65 years, with American Society of Anesthesiologists of 1 to 2 were randomly assigned to 3 groups: sugammadex 2 mg/kg (Group S), sugammadex 1 m/kg with neostigmine 20 µg/kg + atropine 10 µg/kg (Group S1N), and sugammadex 1.5 mg/kg with neostigmine 20 µg/kg + atropine 10 µg/kg (Group S2N), for reversal at the end of surgery during moderate block (train-of-four [TOF] count 1-2). Propofol, remifentanil, rocuronium, and sevoflurane were used for general anesthesia, and neuromuscular function was assessed using kinemyography. The primary outcomes assessed the effects of sugammadex alone and in combination with neostigmine on the time to first flatus. The secondary outcomes included time to first defecation and recovery time; defined as the administration of reversal agent to TOF ratio 90%., Results: Data from 90 female patients who underwent abdominal gynecological surgery were analyzed. No significant differences were found between the groups in term of the time to first flatus, defecation, or postoperative nausea and vomiting after surgery. However, significant differences were observed in the time to reach a TOF ratio 90% (P < .001) and extubation time (P = .003)., Conclusion: The addition of neostigmine to sugammadex did not affect bowel function recovery. However, combining 20 μg/kg neostigmine with 1.5 mg/kg sugammadex or 2 mg/kg sugammadex alone antagonized moderate-depth nondepolarizing neuromuscular blockade with similar efficacy., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The optimal pharmacological reversal strategy for neuromuscular blockade remains undefined even in the setting of strong recommendations for quantitative neuromuscular monitoring by several national and international anesthesiology societies. We evaluated a protocol for managing rocuronium blockade and reversal, using quantitative monitoring to guide choice of reversal agent and to confirm full reversal before extubation., Methods: We conducted a prospective cohort study and enrolled 200 patients scheduled for elective surgery involving the intraoperative use of rocuronium. Providers were asked to adhere to a protocol that was similar to local practice recommendations for neuromusculalr block reversal that had been used for >2 years; the protocol added quantitative monitoring that had not previously been routinely used at our institution. In this study, providers used electromyography-based quantitative monitoring. Pharmacological reversal was accomplished with neostigmine if the train-of-four (TOF) ratio was 0.40 to 0.89 and with sugammadex for deeper levels of blockade. The primary end point was the incidence of postoperative residual neuromuscular blockade (PRNB), defined as TOF ratio <0.9 at time of extubation. We further evaluated the difference in pharmacy costs had all patients been treated with sugammadex., Results: A total of 189 patients completed the study: 66 patients (35%) were reversed with neostigmine, 90 patients (48%) with sugammadex, and 33 (17%) patients recovered spontaneously without pharmacological reversal. The overall incidence of residual paralysis was 0% (95% CI, 0-1.9). The total acquisition cost for all reversal drugs was United States dollar (USD) 11,358 (USD 60 per patient) while the cost would have been USD 19,312 (USD 103 per patient, 70% higher) if sugammadex had been used in all patients., Conclusions: A protocol that includes quantitative monitoring to guide reversal with neostigmine or sugammadex and to confirm TOF ratio ≥0.9 before extubation resulted in the complete prevention of PRNB. With current pricing of drugs, the selective use of sugammadex reduced the total cost of reversal drugs compared to the projected cost associated with routine use of sugammadex for all patients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Competing Interests: Conflicts of Interest: See Disclosures at the end of the article.

Although current clinical practice guidelines have discordant conclusions, a judicious approach to using NMBA infusions may include reserving their use for patients with early severe ARDS who are already deeply sedated and for patients under light sedation who have significant ventilator dyssynchrony, despite attempts to adjust both ventilator settings and sedation requirements. Based on current evidence, the duration of NMBA use should be limited to 48 hours, whenever possible., Competing Interests: Disclosure Drs K.E.A. Burns and S.N. Myatra have no financial or nonfinancial conflicts of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The correct use of muscle relaxants and neuromuscular monitoring during anesthesia has been subject of controversial discussions for decades. Particularly important in clinical practice are identification and management of residual neuromuscular blockages and avoidance of associated complications. Despite the differences in the molecular mechanisms of action between depolarizing and non-depolarizing muscle relaxants the blockade of the postsynaptic nicotinic acetylcholine receptor remains a common ending pathway. Due to its unfavorable side effect profile, succinylcholine should only be used in justified exceptional cases. The use of muscle relaxants generally reduces the complication rate in airway management. However, even the single use of muscle relaxants increases the likelihood of postoperative pulmonary complications. These complications associated with the use of muscle relaxants, such as residual neuromuscular blockade, must be anticipated. The application of guideline-based approaches, including continuous neuromuscular monitoring and the application of muscle relaxant reversal agents, may significantly reduce the rate of adverse events associated with the use of muscle relaxants., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht‐Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein Erklärung zu nichtfinanziellen Interessen DGAI, Wissenschaftliche Arbeitskreise Neuroanästhesie, Gynäkologie und Geburtshilfe ESAIC EMHG, (Thieme. All rights reserved.)

The administration of neuromuscular blocking agents has been used in anesthesia for decades and continues to play an important role in modern anesthesia. Special patient populations, such as very young or very old patients, require adapted use. The following article discusses the specifics of neuromuscular blocking agents administration in geriatric patients., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht‐Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein Erklärung zu nichtfinanziellen Interessen DGAI; Wissenschaftlicher Arbeitskreis Kardioanästhesie; Wissenschaftlicher Arbeitskreis Kinderanästhesie; Paul-Ehrlich-Gesellschaft für Chemotherapie e.V.; Marburger Bund, (Thieme. All rights reserved.)

The administration of muscle relaxants has been used in anesthesia for decades and continues to play an important role in modern anaesthesia. Special patient populations, such as infants or very young patients require adapted use. The article discusses the specifics of muscle relaxant administration in these patient groups., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht‐Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein Erklärung zu nichtfinanziellen Interessen Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

The management of sedation in intensive care medicine has changed substantially in the last few years. Neuromuscular blocking agents (NMBA) are only rarely indicated in modern intensive care medicine. In this review, the mechanism of action, potential side effects, and special considerations for the application of NMBA to critically ill patients will be discussed. We further present the rationale for the use of NMBA for the remaining indications, such as endotracheal intubation, selected cases of severe acute respiratory distress syndrome, and shivering during temperature control after cardiac arrest. The review will close with a description of potential side effects of NMBA use in the intensive care setting, such as awareness, acquired skeletal muscle weakness as well as corneal injuries, and how monitoring of sedation and peripheral muscle blockade may be handled., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: nein; Honorar/geldwerten Vorteil für Referententätigkeit erhalten: nein; Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Nicht‐Sponsor der Veranstaltung): nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an Firma (Sponsor der Veranstaltung): nein Erklärung zu nichtfinanziellen Interessen CJ ist Mitglied in der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin (DGAI)., (Thieme. All rights reserved.)

Background: The accuracy and precision of currently available, widely used acceleromyograph and electromyograph neuromuscular blockade monitors have not been well studied. In addition, the normalization of the train-of-four ratio from acceleromyography (train-of-four ratio [T4/T1] divided by the baseline train-of-four ratio) has not been validated in comparison to mechanomyography., Methods: Enrolled patients had surgery under general anesthesia with a supraglottic airway and without any neuromuscular blocking drugs. Three acceleromyograph monitors, three electromyograph monitors, and a mechanomyograph built in the authors' laboratory were tested. Most patients had an electromyograph and the mechanomyograph on one arm and a third monitor on the contralateral arm. Train-of-four ratios were collected every 12 to 20 s for the duration of the anesthetic. At least 1,000 train-of-four ratios were recorded for each device. Gauge repeatability and reproducibility analysis was performed., Results: Twenty-eight patients were enrolled. In total, 9,498 train-of-four ratio measurements were collected. Since no neuromuscular blocking drugs were used, the expected train-of-four ratio was 1.0. All of the acceleromyograph monitors produced overshoot in the train-of-four ratio (estimated means, 1.10 to 1.13) and substantial variability (gauge SDs, 0.07 to 0.18). Normalization of the train-of-four ratio measured by acceleromyography improved the estimated mean for each device (0.97 to 1.0), but the variability was not improved (gauge SDs, 0.06 to 0.17). The electromyograph and the mechanomyograph monitors produced minimal overshoot (estimated means, 0.99 to 1.01) and substantially less variation (gauge SDs, 0.01 to 0.02). For electromyography and mechanomyography, 0.3% of all train-of-four ratios were outside of the range 0.9 to 1.1. For acceleromyography, 27 to 51% of normalized train-of-four ratios were outside the range of 0.9 to 1.1., Conclusions: Three currently available acceleromyograph monitors produced overshoot and substantial variability that could be clinically significant. Normalization corrected the overshoot in the average results but did not reduce the wide variability. Three electromyograph monitors measured the train-of-four ratio with minimal overshoot and variability, similar to a mechanomyograph., (Copyright © 2024 American Society of Anesthesiologists. All Rights Reserved.)

Background: The neuromuscular blocking agent mivacurium can be used during anesthesia to facilitate tracheal intubation. Data on onset time, duration of action, and effect on intubating conditions in patients 80 years and older are however limited. We hypothesized that onset time and duration of action of mivacurium would be longer in elderly patients than in younger adults., Methods: This prospective observational study included 35 elderly (≥80 years) and 35 younger (18-40 years) patients. Induction of anesthesia comprised fentanyl 1-3 μg kg -1 and propofol 1.5-2.5 mg kg -1 and propofol and remifentanil for maintenance. Acceleromyography was used for monitoring neuromuscular blockade. The primary outcome was onset time defined as time from injection of mivacurium 0.2 mg kg -1 to a train-of-four (TOF) count of zero. Other outcomes included duration of action (time to TOF ratio ≥0.9), intubating conditions using the Fuchs-Buder scale and the intubating difficulty scale (IDS), and occurrence of hoarseness and sore throat postoperatively., Results: No difference was found in onset time comparing elderly with younger patients; 219 s (SD 45) versus 203 s (SD 74) (difference: 16 s (95% CI: -45 to 14), p = .30). Duration of action was significantly longer in elderly patients compared with younger patients; 52 min (SD 17) versus 30 min (SD 8) (difference: 22 min [95% CI: 15 to 28], p < .001). No difference was found in the proportion of excellent intubating conditions (Fuchs-Buder); 31/35 (89%) versus 26/35 (74%) (p = .12) or IDS score (p = .13). A larger proportion of younger patients reported sore throat 24 h postoperatively; 34% versus 0%, p = .0002. No difference was found in hoarseness., Conclusion: No difference in onset time of mivacurium 0.2 mg kg -1 was found comparing elderly and younger patients. However, elderly patients had significantly longer duration of action. No difference was found in intubating conditions., (© 2024 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.)

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., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Anesthesiologists.)

Purpose: Post-operative urinary retention (POUR) is a known complication of hernia surgery. Minimally invasive inguinal hernia repair (IHR) is typically done under general anesthesia with neuromuscular blockade (NMB), which is commonly reversed with an anticholinesterase inhibitor paired with an anticholinergic agent. Sugammadex is a unique NMB reversal agent that does not have to be paired with an anticholinergic. We sought to explore the role of sugammadex in reducing the rate of POUR following these procedures., Methods: Data were collected retrospectively at a single institution between February 2016 and October 2019. We identified and studied patients who underwent minimally invasive IHR and received either sugammadex or neostigmine/glycopyrrolate for NMB reversal. The primary endpoint was POUR requiring bladder catheterization. Secondary endpoints included post-operative and 30-day readmissions., Results: 274 patients were included in this study (143 received neostigmine and glycopyrrolate, 131 sugammadex). The sugammadex patients were on average 5 years older than the neostigmine/ glycopyrrolate patients (63.2 vs 58.2, p = 0.003), and received less median intravenous fluids (IVF) (900 ml vs 1000 ml; p = 0.015). There was a significant difference in the rate of POUR between the sugammadex and neostigmine/glycopyrrolate patients (0.0% vs 8.4%, p ≤ 0.001). The difference remained significant after controlling for age and IVF. The odds of POUR for those who received neostigmine/glycopyrrolate were 25 × higher than the odds of those who received sugammadex., Conclusion: The results of this study reflect the protective role of sugammadex against POUR in minimally invasive IHR cases., (© 2024. The Author(s), under exclusive licence to Springer-Verlag France SAS, part of Springer Nature.)

Background: Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta-analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients., Method: We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results., Results: We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance., Conclusions: The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent., (© 2024 John Wiley & Sons Ltd.)

Background: Prolong effects of non-depolarizing neuromuscular blocking agents after rapid sequence intubation may prevent meaningful neurological examination, delaying appropriate diagnosis and neurosurgical intervention. Sugammadex is indicated for the reversal of neuromuscular blockade induced by rocuronium. Objective: The objective of this study was to evaluate low- (2 mg/kg) vs standard-dose (4 mg/kg) sugammadex for rocuronium-induced deep neuromuscular blockade reversal in the emergency department (ED) by achieving a post-treatment train-of-four (TOF) of 4 to facilitate neurological examination. Methods: This was a single-center, retrospective, cohort study evaluating low-vs standard-dose sugammadex for neuromuscular blockade reversal in the ED. Results: 34 patients were identified within the designated time period, 24 of which were included in the final analysis ([n = 9 low-dose], [n = 15 standard-dose]). Median sugammadex doses were 2.3 mg/kg and 4.1 mg/kg for low- and standard-dose, respectively. The majority of patients presented for intraparenchymal hemorrhage (54.2%). No significant difference in success rate of NMBA reversal was found between low- and standard-dose sugammadex ([100.0% vs 93.3%], P = 1.000). A total of 9 patients had a neurosurgical procedure performed after sugammadex administration. Low-dose sugammadex was associated with significantly less acquisition cost compared to the standard dose ( P < .001). Conclusion: Low- (2 mg/kg) and standard-dose (4 mg/kg) sugammadex successfully reversed rocuronium-induced deep neuromuscular blockade in the ED by achieving a post-treatment TOF of 4 to facilitate neurologic examination. Low-dose sugammadex may be a viable option for deep NMBA reversal in the ED and is associated with decreased institutional cost., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Low-pressure pneumoperitoneum (LPP) is an attempt to improve laparoscopic surgery. Lower pressure causes lesser inflammation and better hemodynamics. There is a lack of literature comparing inflammatory markers in LPP with deep NMB to standard pressure pneumoperitoneum (SPP) with moderate NMB in laparoscopic cholecystectomy., Methodology: This was a single institutional prospective randomized control trial. Participants included all patients undergoing laparoscopic cholecystectomy for symptomatic gall stone disease. Participants were divided into 2 groups group A and B. Group A-Low-pressure group in which pneumoperitoneum pressure was kept low (8-10 mmHg) with deep Neuromuscular blockade (NMB) and Group B-Normal pressure group (12-14 mmHg) with moderate NMB. A convenience sample size of 80 with 40 in each group was selected. Lab investigations like CBC, LFT, RFT and serum IL-1, IL-6, IL-17, TNF alpha levels were measured at base line and 24 h after surgery and compared using appropriate statistical tests. Other parameters like length of hospital stay, post-operative pain score, conversion rate (low-pressure to standard pressure), and complications were also compared., Results: Eighty participants were analysed with 40 in each group. Baseline characteristics and investigations were statistically similar. Difference (post-operative-pre-operative) of inflammatory markers were compared between both groups. Numerically there was a slightly higher rise in most of the inflammatory markers (TLC, ESR, CRP, IL-6, TNFα) in Group B compared to Group A but not statistically significant. Albumin showed significant fall (p < 0.001) in Group B compared to Group A. Post-operative pain was also significantly less (p < 0.001) in Group A compared to Group B at 6 h and 24 h. There were no differences in length of hospital stay and incidence of complications. There was no conversion from low-pressure to standard pressure., Conclusion: Laparoscopic cholecystectomy performed under low-pressure pneumoperitoneum with deep NMB may have lesser inflammation and lesser post-operative pain compared to standard pressure pneumoperitoneum with moderate NMB. Future studies with larger sample size need to be designed to support these findings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Patients with neurologic injuries often receive neuromuscular blocking agents to facilitate airway management. The urgent nature of intubation may result in paralytic administration prior to neurologic examination, delaying clinical assessment, prognostication, and surgical interventions. Objective: In October 2018, an institutional guideline was implemented to extend institutional sugammadex use to include patients with uncertain neurologic examinations with recent rocuronium administration. The guideline allowed for a dose range of 2 mg/kg to 16 mg/kg. The objective of this continuous quality improvement project was to describe the use of sugammadex after implementation of an institutional guideline. Methods: Patient records between October 2018 and March 2020 were reviewed for guideline adherence and outcomes. Information assessed included patient weight, injury mechanism, the dosage and timing of rocuronium and sugammadex administration, and neurologic examination findings. Descriptive statistics were used to assess outcomes. Results: During the study period, eleven patients received sugammadex to facilitate neurologic examinations. The most common dose of sugammadex was 4 mg/kg with a mean total dose of 498.4 ± 333.5 mg. The mean time between rocuronium and sugammadex administration was 73.9 ± 41 minutes. Most patients (72.7%) had definitive changes in neurologic examination after sugammadex administration. Five patients had neurosurgical interventions offered and performed, with 1 of the patients surviving. Conclusions: This case series suggests that sugammadex is useful for reversing rocuronium induced paralysis to facilitate neurologic examination needed to determine management strategies for patients with a neurologic injury., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Muscle relaxants and their reverse drugs should be carefully administered to patients with acute polymyositis and/or dermatomyositis. However, the use of these drugs in controlled polymyositis and/or dermatomyositis is controversial. This case report describes the use of rocuronium and sugammadex in a 27-year-old female patient with controlled polymyositis who was scheduled for minor oral surgery under general anesthesia. General anesthesia was induced rapidly, and 0.66 mg/kg of rocuronium was administered prior to nasotracheal intubation. No additional muscle relaxants were administered during the surgery. At the end of surgery, approximately 2 hours after the rocuronium was administered, her train-of-four (TOF) ratio was still 49%. A dose of 3.3 mg/kg of sugammadex was administered, and it took 12 minutes for the TOF ratio to exceed 90%. The prolonged duration of muscle relaxation in patients with polymyositis may be due to a decrease in skeletal muscle and capillary volume. The slow onset of sugammadex may be caused by slow diffusion of rocuronium from the neuromuscular junction. Patients with polymyositis require close perioperative neuromuscular function monitoring, regardless of their disease control status.

Background: Peripheral nerve stimulation with a train-of-four (TOF) pattern can be used intraoperatively to evaluate the depth of neuromuscular block and confirm recovery from neuromuscular blocking agents (NMBAs). Quantitative monitoring can be challenging in infants and children due to patient size, equipment technology, and limited access to monitoring sites. Although the adductor pollicis muscle is the preferred site of monitoring, the foot is an alternative when the hands are unavailable. However, there is little information on comparative evoked neuromuscular responses at those 2 sites., Methods: Pediatric patients undergoing inpatient surgery requiring NMBA administration were studied after informed consent. Electromyographic (EMG) monitoring was performed simultaneously in each participant at the hand (ulnar nerve, adductor pollicis muscle) and the foot (posterior tibial nerve, flexor hallucis brevis muscle)., Results: Fifty patients with a mean age of 3.0 ± standard deviation (SD) 2.9 years were studied. The baseline first twitch amplitude (T1) of TOF at the foot (12.46 mV) was 4.47 mV higher than at the hand (P <.0001). The baseline TOF ratio (TOFR) before NMBA administration and the maximum TOFR after antagonism with sugammadex were not different at the 2 sites. The onset time until the T1 decreased to 10% or 5% of the baseline value (T1) was delayed by approximately 90 seconds (both P =.014) at the foot compared with the hand. The TOFR at the foot recovered (TOFR ≥0.9) 191 seconds later than when this threshold was achieved at the hand (P =.017). After antagonism, T1 did not return to its baseline value, a typical finding with EMG monitoring, but the fractional recovery (maximum T1 at recovery divided by the baseline T1) at the hand and foot was not different, 0.81 and 0.77, respectively (P =.68). The final TOFR achieved at recovery was approximately 100% and was not different between the 2 sites., Conclusions: Although this study in young children demonstrated the feasibility of TOF monitoring, interpretation of the depth of neuromuscular block needs to consider the delayed onset and the delayed recovery of TOFR at the foot compared to the hand. The delay in achieving these end points when monitoring the foot may impact the timing of tracheal intubation and assessment of adequate recovery of neuromuscular block to allow tracheal extubation (ie, TOFR ≥0.9)., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2024 International Anesthesia Research Society.)

Aims: Residual neuromuscular blockade has been linked to pulmonary complications in the postoperative period. This study aimed to determine whether sugammadex was associated with a lower risk of postoperative pulmonary complications (PPCs) compared with neostigmine., Methods: This retrospective cohort study was conducted in a tertiary academic medical center. Patients ≥18 year of age undergoing noncardiac surgical procedures with general anesthesia and mechanical ventilation were enrolled between January 2019 and September 2021. We identified all patients receiving rocuronium and reversal with neostigmine or sugammadex via electronic medical record review. The primary endpoint was a composite of PPCs (including pneumonia, atelectasis, respiratory failure, pulmonary embolism, pleural effusion, or pneumothorax). The incidence of PPCs was compared using propensity score analysis., Results: A total of 1786 patients were included in this study. Among these patients, 976 (54.6%) received neostigmine, and 810 (45.4%) received sugammadex. In the whole sample, PPCs occurred in 81 (4.54%) subjects (7.04% sugammadex vs. 2.46% neostigmine). Baseline covariates were well balanced between groups after overlap weighting. Patients in the sugammadex group had similar risk (overlap weighting OR: 0.75; 95% CI: 0.40 to 1.41) compared to neostigmine. The sensitivity analysis showed consistent results. In subgroup analysis, the interaction P-value for the reversal agents stratified by surgery duration was 0.011., Conclusion: There was no significant difference in the rate of PPCs when the neuromuscular blockade was reversed with sugammadex compared to neostigmine. Patients undergoing prolonged surgery may benefit from sugammadex, which needs to be further investigated., (© 2024 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Competing Interests: The author declares no conflict of interest.

Introduction: Sugammadex, a novel selective antagonist of non-depolarizing neuromuscular blocking agents, has been shown to rapidly and effectively reverse moderate and deep paralysis in adults and pediatric patients over age 2, improving patient recovery and reducing the risk of postoperative complications., Areas Covered: Since the use of sugammadex in patients under age 2 is not widely studied, we aim to provide an overview on the drug's application and potential use in infants and neonates. There is a limited but growing body of evidence for the safe, efficacious use of sugammadex in children under age 2. Relevant studies were identified from the most updated data including case reports, clinical trials, systematic reviews, and meta analyses., Expert Opinion: The results suggest that at a dose of 2 to 4 mg/kg of sugammadex can be safely used to rapidly and effectively reverse neuromuscular blockade in neonates and infants; it is non-inferior based on incidence of adverse events compared to neostigmine. Additionally, sugammadex doses between 8 and 16 mg/kg may be used as a rescue agent for infants during 'can't intubate, can't ventilate' crisis. Overall, sugammadex offers new value in the perioperative care of patients under age 2, with further studies warranted to better understand its application and full effect in the pediatric population.

Purpose: To determine the effect of tetanic stimulation on the time to achieve stabilization of the T1 height, by acceleromyography train-of-four (TOF) ratio monitoring, in patients aged 60 to 80 years., Methods: Randomized, prospective, single-blind, controlled trial in patients aged 60 to 80 years undergoing elective surgery under general anesthesia in two university hospitals in Brazil between December 2019 and March 2022. This trial was performed in accordance with the principles of the Helsinki Declaration and the guidelines for good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II. Participants were randomly allocated by computer-generated numbers to receive tetanic stimulation (intervention group, n  =  25) or not receive tetanic stimulation (control group, n  =  25) to achieve T1 height stabilization on TOF ratio monitoring. The primary endpoint was to evaluate the effect of tetanic stimulation on the time to achieve stabilization of the T1 height. We also evaluated the effect on the onset time of rocuronium and time to recover from neuromuscular blockade with a single dose of rocuronium 0.6 mg.kg-1 with spontaneous recovery., Results: There was no statistically significant difference between the groups in the time to T1 height stabilization (intervention: 4.3 [2.0-8.0] min; control: 5.8 [2.0-10.5] min; p  =  0.202), onset time of the neuromuscular blocking agent (intervention: 1.9 [±0.7] min; control: 2.2 [±1.0] min; p  =  0.219), or neuromuscular blockade recovery times to normalized TOF values of 0.7 (intervention: 106.1 [±37.2] min; control: 91.7 [±27.5] min; p  =  0.295), 0.8 (intervention: 114.3 [±40.1] min; control: 97.8 [±28.9] min; p  =  0.225), 0.9 (intervention: 126.5 [±44.0] min; control: 106.9 [±30.6] min; p  =  0.153), and 1.0 (intervention: 138.3 [±43.4] min; control: 123.8 [±43.5] min; p  =  0.425)., Conclusion: The results of this study suggest that the recommendation to use tetanic stimulation to shorten the time to T1 height stabilization in neuromuscular monitoring did not alter the stabilization time of the T1 twitch or the pharmacodynamics of neuromuscular blockade with rocuronium in patients aged 60 to 80 years., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Henrique Silva Ribeiro et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Myocardial injury after non-cardiac surgery (MINS) is a common and serious complication in older patients. This study investigates the impact of neuromuscular block on the MINS incidence and other cardiovascular complications in the early postoperative stage of older patients undergoing laparoscopic colorectal cancer resection., Methods: 70 older patients who underwent laparoscopic colorectal cancer resection were separated into the deep neuromuscular block group and moderate neuromuscular block group for 35 cases in each group (n = 1:1). The deep neuromuscular block group maintained train of four (TOF) = 0, post-tetanic count (PTC) 1-2, and the moderate neuromuscular block group maintained TOF = 1-2 during the operation. Sugammadex sodium was used at 2 mg/kg or 4 mg/kg for muscle relaxation antagonism at the end of surgery. The MINS incidence was the primary outcome and compared with Fisher's exact test. About the secondary outcomes, the postoperative pain was analyzed with Man-Whitney U test, the postoperative nausea and vomiting (PONV) and the incidence of cardiovascular complications were analyzed with Chi-square test, intraoperative mean artery pressure (MAP) and cardiac output (CO) ratio to baseline, length of stay and dosage of anesthetics were compared by two independent samples t-test., Results: MINS was not observed in both groups. The highest incidence of postoperative cardiovascular complications was lower limbs deep vein thrombosis (14.3% in deep neuromuscular block group and 8.6% in moderate neuromuscular group). The numeric rating scale (NRS) score in the deep neuromuscular block group was lower than the moderate neuromuscular block group 72 h after surgery (0(1,2) vs 0(1,2), P = 0.018). The operation time in the deep neuromuscular block group was longer (356.7(107.6) vs 294.8 (80.0), min, P = 0.008), the dosage of propofol and remifentanil was less (3.4 (0.7) vs 3.8 (1.0), mg·kg -1 ·h -1 , P = 0.043; 0.2 (0.06) vs 0.3 (0.07), μg·kg -1 ·min -1 , P < 0.001), and the length of hospital stay was shorter than the moderate neuromuscular block group (18.4 (4.9) vs 22.0 (8.3), day, P = 0.028). The differences of other outcomes were not statistically significant., Conclusions: Maintaining different degrees of the neuromuscular block under TOF guidance did not change the MINS incidence within 7 days after surgery in older patients who underwent laparoscopic colorectal cancer resection., Trial Registration: The present study was registered in the Chinese Clinical Trial Registry (10/02/2021, ChiCTR2100043323)., (© 2024. The Author(s).)

Background: Sugammadex is a pharmacologic agent that provides rapid reversal of neuromuscular blockade via encapsulation of the neuromuscular blocking agent (NMBA). The sugammadex-NMBA complex is primarily cleared through glomerular filtration from the kidney, raising the possibility that alterations in renal function could affect its elimination. In pediatric patients, the benefits of sugammadex have led to widespread utilization; however, there is limited information on its application in pediatric renal impairment. This study examined sugammadex use and postoperative outcomes in pediatric patients with severe chronic renal impairment at our quaternary pediatric referral hospital., Methods: After IRB approval, we performed a retrospective analysis in pediatric patients with stage IV and V chronic kidney disease who received sugammadex from January 2017 to March 2022. Postoperative outcomes studied included new or increased respiratory requirement, unplanned intensive care unit (ICU) admission, postoperative pneumonia, anaphylaxis, and death within 48 h postoperatively, unplanned deferral of intraoperative extubation, and repeat administrations of NMBA reversal after leaving the operating room., Results: The final cohort included 17 patients ranging from 8 months to 16 years old. One patient required new postoperative noninvasive ventilation on postoperative day 2, which was credited to hypervolemia. Another patient had bronchospasm intraoperatively resolving with medication, which could not definitively be associated sugammadex administration. There were no instances of deferred extubation, unplanned ICU or need for supplemental oxygen after tracheal extubation identified., Conclusion: No adverse effects directly attributable to sugammadex in pediatric patients with severe renal impairment were detected. There may be a role for utilization of sugammadex for neuromuscular reversal in this population., (© 2024. The Author(s).)

Background: Postoperative gastrointestinal dysfunction (POGD) commonly occurs following gastrointestinal (GI) surgery and is associated with specific anesthetic agents. Cholinesterase inhibitors employed for reversing neuromuscular blockade have been implicated in development of POGD. Sugammadex, a novel reversal agent, is linked with reduced POGD. However, there is a lack of comprehensive comparative review between these agents regarding their impact on POGD following GI surgery. This study aims to systematically review the effects of sugammadex on POGD compared to cholinesterase inhibitors following GI surgery., Methods: MEDLINE, EMBASE, and CENTRAL were searched as of July 2022 to identify articles comparing sugammadex with cholinesterase inhibitors in patients undergoing gastrointestinal surgery, specifically in relation to POGD. Secondary endpoints included length of hospital stay, readmission rates, pulmonary complications, and postoperative morbidity., Results: From 198 citations, 2 randomized controlled trials (RCTs) and 3 retrospective cohorts with 717 patients receiving sugammadex and 812 patients receiving cholinesterase inhibitors were included. Significantly lower rates of prolonged postoperative ileus (OR .44, 95% CI .25-.77, P < .05, I 2 = 56%, low certainty evidence) was observed with sugammadex. No significant difference in any other outcome was observed. Narrative review of readmission data demonstrated no significant difference., Conclusion: The use of sugammadex following gastrointestinal surgery is associated with significantly lower rates of prolonged postoperative ileus compared to cholinesterase inhibitors. However, these do not translate into a significant reduction in length of stay, morbidity, or postoperative nausea and vomiting. Results are limited by the numer of studies included and missing data, more robust RCTs are needed before recommendations can be made., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Monitoring the electroencephalogram (EEG) during general anesthesia can help to safely navigate the patient through the procedure by avoiding too deep or light anesthetic levels. In daily clinical practice, the EEG is recorded from the forehead and available neuromonitoring systems translate the EEG information into an index inversely correlating with the anesthetic level. Electrode placement on the forehead can lead to an influence of electromyographic (EMG) activity on the recorded signal in patients without neuromuscular blockade (NMB). A separation of EEG and EMG in the clinical setting is difficult because both signals share an overlapping frequency range. Previous research showed that indices decreased when EMG was absent in awake volunteers with NMB. Here, we investigated to what extent the indices changed, when EEG recorded during surgery with NMB agents was superimposed with EMG., Methods: We recorded EMG from the flexor muscles of the forearm of 18 healthy volunteers with a CONOX monitor during different activity settings, that is, during contraction using a grip strengthener and during active diversion (relaxed arm). Both the forehead and forearm muscles are striated muscles. The recorded EMG was normalized by z -scoring and added to the EEG in different amplification steps. The EEG was recorded during anesthesia with NMB. We replayed these combined EEG and EMG signals to different neuromonitoring systems, that is, bispectral index (BIS), CONOX with qCON and qNOX, and entropy module with state entropy (SE) and response entropy (RE). We used the Friedman test and a Tukey-Kramer post hoc correction for statistical analysis., Results: The indices of all neuromonitoring systems significantly increased when the EEG was superimposed with the contraction EMG and with high EMG amplitudes, the monitors returned invalid values, representative of artifact contamination. When replaying the EEG being superimposed with "relaxed" EMG, the qCON and BIS showed significant increases, but not SE and RE. For SE and RE, we observed an increased number of invalid values., Conclusions: With our approach, we could show that EMG activity during contraction and resting state can influence the neuromonitoring systems. This knowledge may help to improve EEG-based patient monitoring in the future and help the anesthesiologist to use the neuromonitoring systems with more knowledge regarding their function., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 International Anesthesia Research Society.)

Background: Deep neuromuscular blockade (NMB) has benefits in various surgical procedures, however, precise quantitative neuromuscular monitoring is crucial for its proper maintenance and recovery. Neuromuscular blocking agent dosage relies on actual body weight (ABW), but this varies among individuals. Therefore, this study hypothesizes that there is a correlation between the rocuronium requirement for deep NMB and muscle mass ratio measured by bioelectric impedance analysis., Methods: Ninety adult female patients undergoing laparoscopic operation were enrolled in this study. Muscle and fat masses were assessed using a body composition analyser. Deep NMB, defined as a post-tetanic count of 1-2, was maintained through the continuous infusion of rocuronium. The primary outcome involves determining the correlation between the rocuronium dose required for deep NMB and the muscle mass ratio. Conversely, secondary outcomes included assessing the relationship between the rocuronium dose for deep NMB and fat mass ratio, and ABW. Additionally, we investigated their relationship with rocuronium onset time and profound blockade duration., Results: No relationship was observed between the muscle mass ratio and rocuronium dose required for maintaining deep NMB (r = 0.059 [95% CI = 0.153-0.267], p = 0.586). Fat mass ratio and ABW showed no correlation with the rocuronium dose, whereas rocuronium onset time was positively correlated with muscle mass ratio (r = 0.327) and negatively correlated with fat mass ratio (r = -0.302), respectively. Profound blockade duration showed no correlation with any of the assessed variables., Conclusions: No correlation was detected between muscle mass ratio and the rocuronium dose required to achieve deep NMB., (Copyright © 2024. Published by Elsevier Masson SAS.)

Purpose: The impact of the combination of abdominal peripheral nerve block (PNB) and the depth of neuromuscular blockade on the surgical field were assessed., Methods: Thirty-eight patients undergoing elective robot-assisted laparoscopic radical prostatectomy (RARP) were randomized into two groups: a PNB group (moderate neuromuscular block [train-of-four 1-3 twitches] with abdominal PNB) and a non-PNB group (deep neuromuscular block [post-tetanic count 0-2 twitches] without abdominal PNB). The primary outcome was the change in the depth of the abdominal cavity relaxation assessed by the change in the distance (Δdistance) between the umbilicus port and peritoneum upon pneumoperitoneal pressure increase from 8 to 12 mmHg. The secondary outcomes were the CO 2 usage for the pneumoperitoneal pressure increase and the subjective differences in the Surgical Rating Score (SRS) during surgery., Results: The Δdistance and the CO 2 usage from 8 to 12 mmHg did not differ significantly between the non-PNB and PNB groups (1.34 ± 0.65 vs. 1.28 ± 0.61 cm, p = 0.763 and 3.64 ± 1.68 vs. 4.34 ± 1.44 L, p = 0.180, respectively). There was also no significant difference in SRS. Comparisons of the Δdistance values for pressure increases from 6 to 8 mmHg, 6 to 10 mmHg and 6 to 12 mmHg between the non-PNB and PNB groups also showed no between-group differences, despite significant intra-group differences (p < 0.001) by pressure increment., Conclusions: Our findings indicate that moderate neuromuscular block with abdominal PNB maintained an adequate surgical space for RARP, with no significant difference from the space achieved by deep neuromuscular block., (© 2024. The Author(s) under exclusive licence to Japanese Society of Anesthesiologists.)

Introduction: The effect of neuromuscular blocking agents may be reversed by administration of neostigmine, when two twitches are present using train-of-four (TOF) stimulation. However, in elderly patients, limited data are available about when to administer neostigmine. We hypothesised that time to two twitches after TOF (TOF-2) was shorter after rocuronium 0.6 mg/kg than after rocuronium 0.9 mg/kg. Also, we hypothesised that time to TOF-2 would be shorter after rocuronium 0.3 mg/kg than after rocuronium 0.6 mg/kg., Methods: This was a secondary analysis of 50 elderly patients > 80 years; 16 patients received rocuronium 0.6 mg/kg, another 16 patients received rocuronium 0.9 mg/kg; and, finally, 18 patients received rocuronium 0.3 mg/kg. Patients received total intravenous anaesthesia, and neuromuscular block was monitored with acceleromyography., Results: Time to TOF-2 was shorter after rocuronium 0.6 mg/kg than after rocuronium 0.9 mg/kg: 37 min. versus 59 min. (difference: 22 min. (95% confidence intervals (CI): 10 to 33 min.), p = 0.0007). Time to TOF-2 after rocuronium 0.3 mg/kg was shorter than after rocuronium 0.6 mg/kg: 19 min. versus 37 min. (difference: 18 min. (95% CI: 11 to 25 min.), p = 0.00006). However, only 33% of the patients receiving 0.3 mg/kg obtained full effect i.e. TOF-0., Conclusion: Time to TOF-2 was shorter after rocuronium 0.6 mg/kg than after 0.9 mg/kg and shorter after rocuronium 0.3 mg/kg than after 0.6 mg/kg., Funding: This work was supported by departmental sources., Trial Registration: This study was a secondary analysis of two clinical trials., Clinicaltrials: gov (NCT04512313), (NCT03857750)., (Published under Open Access CC-BY-NC-BD 4.0. https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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.

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., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Objectives: Mechanical ventilation (MV) is pervasive among critically ill children. We sought to validate a computerized physiologic equation to predict minute ventilation requirements in children and test its performance against clinician actions in an in silico trial., Design: Retrospective, electronic medical record linkage, cohort study., Setting: Quaternary PICU., Patients: Patients undergoing invasive MV, serial arterial blood gas (ABG) analysis within 1-6 hours, and pharmacologic neuromuscular blockade (NMB)., Measurements and Main Results: ABG values were filtered to those occurring during periods of NMB. Simultaneous ABG and minute ventilation data were linked to predict serial Pa co2 and pH values using previously published physiologic equations. There were 15,121 included ABGs across 500 encounters among 484 patients, with a median (interquartile range [IQR]) of 20 (10-43) ABGs per encounter at a duration of 3.6 (2.1-4.2) hours. The median (IQR) Pa co2 prediction error was 0.00 (-3.07 to 3.00) mm Hg. In Bland-Altman analysis, the mean error was -0.10 mm Hg (95% CI, -0.21 to 0.01 mm Hg). A nested, in silico trial of ABGs meeting criteria for weaning (respiratory alkalosis) or escalation (respiratory acidosis), compared the performance of recommended ventilator changes versus clinician decisions. There were 1,499 of 15,121 ABGs (9.9%) among 278 of 644 (43.2%) encounters included in the trial. Calculated predictions were favorable to clinician actions in 1124 of 1499 ABGs (75.0%), equivalent to clinician choices in 26 of 1499 ABGs (1.7%), and worse than clinician decisions in 349 of 1499 ABGs (23.3%). Calculated recommendations were favorable to clinician decisions in sensitivity analyses limiting respiratory rate, analyzing only when clinicians made changes, excluding asthma, and excluding acute respiratory distress syndrome., Conclusions: A computerized equation to predict minute ventilation requirements outperformed clinicians' ventilator adjustments in 75% of ABGs from critically ill children in this retrospective analysis. Prospective validation studies are needed., Competing Interests: Drs. Pelletier, Au, and Horvat’s institutions received support for article research from the National Institutes of Health. Dr. Pelletier’s institution received funding from the National Institute for Child Health and Human Development (NICHD) (5T32HD040686-2). Dr. Au’s institution received funding from the National Institute of Neurological Disorders and Stroke. Dr. Horvat’s institution received funding from the NICHD. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies.)