Optimal dose of neostigmine antagonizing cisatracurium-induced shallow neuromuscular block in elderly patients: a randomized control study.

BACKGROUND: Residual neuromuscular block after using neuromuscular blocking agents is a common and potentially harmful complication of general anesthesia. Neostigmine is a widely used antagonist, but its optimal dose for elderly patients is unclear. OBJECTIVES: To compare the optimal dosage and safety of neostigmine for reversing shallow residual block in elderly patients after cisatracurium-induced neuromuscular block. METHODS: A randomized controlled trial was conducted in 196 elderly patients undergoing non-cardiac surgery under general anesthesia with cisatracurium. Patients were assigned to receive either no neostigmine (control group) or neostigmine at 20 µg/kg, 40 µg/kg or 50 µg/kg when train-of-four (TOF) ratio reached 0.2 at the end of surgery. The primary outcome was the time to reach TOF ratio of 0.9 after administration. Secondary outcomes included TOF ratio at 10 min after administration, postoperative nausea and vomiting, postoperative cognitive impairment and post-anesthesia care unit (PACU) stay time. RESULTS: The time to reach TOF ratio of 0.9 in the 20 µg/kg, 40 µg/kg and 50 µg/kg groups was significantly shorter than the control group (H = 104.257, P < 0.01), and the time of 40 µg/kg group and 50 µg/kg group was significantly shorter than the 20 µg/kg group (P < 0.001). There was no significant difference between 40 µg/kg and 50 µg/kg groups (P = 0.249). The TOF ratio at 10 min after administration showed similar results. There were no significant differences among groups in postoperative nausea and vomiting, postoperative cognitive impairment or post-operation hospital stay. CONCLUSIONS: Timely use of neostigmine after general anesthesia in elderly patients can significantly shorten time of TOF value reaching 0.9, among which 40 µg/kg dosage may be a more optimized choice. TRIAL REGISTRATION: this study was registered on chictr.org.cn (ChiCTR2100054685, 24/12/2021).

Rate of residual neuromuscular block using single-dose rocuronium in general anesthesia for ENT surgery: a retrospective cohort study.

INTRODUCTION: NMB facilitates intubating conditions in general anesthesia. However, it is associated with significant residual postoperative paralysis and morbidity. OBJECTIVE: To investigate the rate of underdiagnosed residual NMB based on two TOFR criteria (< 0.91 and < 1.00). METHODS: We performed a retrospective study adhering to STROBE guidelines. We included patients undergoing ENT surgery using single-dose neuromuscular block for balanced general anesthesia from June to December 2018. We collected demographic and anthropometric data, ASA score, NMBA dose, TOFR recordings at 5, 30 and 60 min and end of the surgery, anesthesia and surgery time, and administration of reversal agent. Statistical analysis included descriptive and dispersion measures statistics, curve and cross tables for residual NMB on different TOFR criteria with sub-analysis for AR, RR, and OR in patients over 65 years old. RESULTS: We included 57 patients, mean age 41; 43 females and 14 males. Mean anesthetic and surgical time were 139.4 and 116.1 min, respectively. All the patients received rocuronium under a mean ponderal single-dose of 0.48 mg/kg. Residual NMB rates were 29.9 and 49.1% for a TOFR < 0.91 and < 1.00, respectively. Older adults had an OR of 6.08 for residual NMB. CONCLUSIONS: The rate of residual NMB was 29.9 to 49.1%, depending on the criteria used (TOFR < 0.91 and < 1.00, respectively). Patients above 65 years old had an increased risk of residual NMB (6.08 OR) and clinical symptoms related to residual NMB (11.75 OR). We recommend future research aiming to provide a specific surveillance protocol for patients above 65 years old, including shorter-action NMB, early reversal, and prolonged surveillance using the TOFR criteria of < 1.00 to identify patients at risk of residual NMB readily.

Routine administration of neostigmine after recovery of spontaneous breathing versus neuromuscular monitor-guided administration of neostigmine in pediatric patients: a parallel, randomized, controlled study.

BACKGROUND: Neostigmine used to reverse the muscle relaxants should be guided by neuromuscular monitoring, as the degree of spontaneous pre-reversal recovery is the key to success to reverse the neuromuscular block. But neuromuscular monitoring is not always available for some patients during anesthesia and, in consequence, we need to use other clinical judgment to guide the use of neostigmine to reverse the neuromuscular block. In this trial, we aimed to evaluate the incidence of residual neuromuscular blockade (rNMB) in pediatric patients with routine use of neostigmine after recovery of spontaneous breathing compared with the patients with the use of neostigmine guided by neuromuscular monitoring. METHODS: A parallel, randomized, controlled noninferiority study was conducted. We enrolled aged 3 months to 12 years old patients who underwent inguinal hernia repair under general anesthesia. The enrolled patients were randomly divided into experimental and control groups. After surgery, children in the experimental group were given 0.02 mg/kg neostigmine after recovery of spontaneous breathing. Children in the control group were given 0.02 mg/kg neostigmine when the train-of-four (TOF) ratio was between 0.4 and 0.9. However, no neostigmine was administered if the TOF ratio was higher than 0.9. The primary outcome was the incidence of rNMB after extubation (TOF ratio < 0.9). Secondary outcomes included the incidence of neostigmine-induced muscle paralysis, end of surgery - extubation interval, end of surgery - exit OR interval, the length of stay in the PACU, the incidence of hypoxia in the PACU, the number of children who required assisted ventilation during the PACU stay, and neostigmine-related adverse events. RESULTS: A total of 120 children were included in this study, with 60 in the experimental group and 60 in the control group. There was no significant difference in the incidence of rNMB after extubation between the groups (45/60 vs 44/60, RR 1.02 [95% CI, 0.83 to 1.26], p = 0.84). There was no neostigmine-induced muscle paralysis in either group. Adverse events were similar occurred in both groups. However, time from end of the surgery to leaving the operating room was earlier in the experimental group than in the control group (13.6 ± 5.2 vs 15.7 ± 5.6 min, MD -2.10 min [95% CI, -3.70 to -0.50], p = 0.04). The risk ratio of the incidence of TOF ratio < 0.3 for the experimental group was 31.12 (95%CI, 1.89 to 512.61) compared with the control group (12/60 vs 0/60, p = 0.00) in exploratory analysis. CONCLUSIONS: Recovery of spontaneous breathing could be used as a substitute of neuromuscular monitoring to guide neostigmine use in pediatric patients following minor surgeries. However, care should be taken for the residual neuromuscular block. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR-IOR-17012890. Registered on 5 October 2017.

Postoperative Risk of Transfusion After Reversal of Residual Neuromuscular Block With Sugammadex Versus Neostigmine: A Retrospective Cohort Study.

BACKGROUND: Sugammadex and neostigmine are routinely used to reverse residual neuromuscular blocks at the end of surgery. Sugammadex has been linked with prolongation of laboratory coagulation markers, but clinical relevance on postoperative blood loss and transfusions remains unclear. METHODS: In this retrospective, single-center, cohort study, we analyzed medical records of adult patients having noncardiac surgery who were given sugammadex or neostigmine from May 2016 to December 2020. Our primary outcome was the incidence of any postoperative transfusion of red blood cells, and/or fresh-frozen plasma, and/or platelets. Secondary outcomes were duration of hospitalization, need for resurgery, and postoperative intensive care unit (ICU) admission. After propensity score weighting, the odds ratio (OR) for postoperative transfusion was assessed in both groups (sugammadex versus neostigmine) using a generalized estimation equation to count within-subject correlation weighted by the inverse propensity score. RESULTS: Out of 39,325 eligible surgeries, 33,903 surgeries in 29,062 patients were included in the analysis; with 4581 patients receiving sugammadex and 29,322 patients receiving neostigmine. The raw incidence of postoperative transfusion was 7.40% in sugammadex and 7.45% in the neostigmine group. After weighting by propensity score, the incidence of postoperative transfusion was 8.01% in the sugammadex and 7.38% in the neostigmine group (OR, 1.11 [95% confidence interval [CI], 0.97-1.26; P = .118]). There was no difference in duration of hospitalization and need for resurgery, but odds of postoperative ICU admission were significantly higher for patients receiving sugammadex than those receiving neostigmine (OR, 1.33 [98.33% CI, 1.17-1.52; P < .0001]). Our a priori planned analysis of coagulation laboratory parameters could not be completed because of a high amount of missing laboratory data. CONCLUSIONS: There is no statistically significant nor clinically important difference in the risk of postoperative transfusion in patients receiving sugammadex or neostigmine.

Residual neuromuscular block in the postanesthesia care unit: incidence, risk factors, and effect of neuromuscular monitoring and reversal agents.

BACKGROUND: The aim of this study was to determine the incidence of residual neuromuscular block (RNMB) in a tertiary care hospital. Secondary goals were to examine the characteristics of the use of intraoperative neuromuscular monitoring (NMM) and different reversal agents by the attending anesthesiologists, and to determine the factors related to the patient and perioperative processes on the development of RNMB. METHODS: The patients' arrival time at the postanesthesia care unit was accepted as point zero (T0). The acceleromyography of the patients' adductor pollicis muscle was monitored for NMM. Train of four ratios (TOFRs) were recorded at 0, 10, 20, and 30 min. A TOFR < 0.9 was defined as RNMB. Patients' demographic and perioperative data were also recorded. RESULTS: A total of 216 patients completed the study. RNMB was observed in 47 patients (21.8%). Seventy-eight patients (36%) were followed up with NMM. Neostigmine and sugammadex were used in 174 (80.5%) and 42 (19.5%) patients, respectively, and they were both underdosed (21.2 ± 3.0 mcg/kg and 1.5 ± 0.7 mg/kg, respectively). Use of neostigmine and absence of NMM were risk factors for RNMB (p: 0.01 and 0.001, respectively) along with the number of additional doses (>1 doses, p ≤ 0.02) and the timing of the last dose of rocuronium (<88 min, p ≤ 0.01). None of the patients who received both NMM and sugammadex experienced RNMB. DISCUSSION: The RNMB incidence was found to be 21.8%. The main reasons of it were the lack of intraoperative NMM and inappropriate use of reversal agents. Despite strong recommendations, the use of NMM is still insufficient and reversal agents are still underdosed.

Residual neuromuscular blockade in the ICU: a prospective observational study and national survey.

Residual neuromuscular blockade is associated with significant morbidity. It has been widely studied in anaesthesia; however, the incidence of residual neuromuscular blockade in patients managed in the ICU is unknown. We conducted a prospective observational study in a tertiary ICU to determine the incidence of residual neuromuscular blockade using quantitative accelerographic monitoring. We tested for residual neuromuscular blockade (defined as a train-of-four ratio < 0.9) before cessation of sedation in anticipation of tracheal extubation. We also surveyed 16 other ICUs in New Zealand to determine their use of neuromuscular monitoring. A total of 191 patients were included in the final analysis. The incidence (95%CI) of residual neuromuscular blockade was 43% (36-50%), with a similar incidence observed in non-postoperative and postoperative patients. There was a lower risk of residual neuromuscular blockade with atracurium than rocuronium (risk ratio (95%CI) of 0.39 (0.12-0.78)) and a higher risk with pancuronium than rocuronium (1.59 (1.06-2.49)). Our survey shows that, in New Zealand ICUs, monitoring of neuromuscular function is rarely carried out before tracheal extubation. When neuromuscular monitoring is undertaken, it is based on individual clinician suspicion and performed using qualitative measurements. No ICU reported using a quantitative monitor or a clinical guideline. The results demonstrate a high incidence of residual neuromuscular blockade in our ICU patients and identify the type of neuromuscular blocking drug as a possible risk factor. Monitoring neuromuscular function before tracheal extubation is not currently the standard of care in New Zealand ICUs. These data suggest that residual neuromuscular blockade may be an under-recognised problem in ICU practice.

Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects.

BACKGROUND: Sugammadex and neostigmine given to reverse residual neuromuscular blockade can cause side effects including bradycardia, anaphylaxis, bronchospasm, and even cardiac arrest. We tested the hypothesis that sugammadex is noninferior to neostigmine on a composite of clinically meaningful side effects, or vice versa. METHODS: We analyzed medical records of patients who had general, cardiothoracic, or pediatric surgery and were given neostigmine or sugammadex from June 2016 to December 2019. Our primary outcome was a collapsed composite of bradycardia, anaphylaxis, bronchospasm, and cardiac arrest occurring between administration of the reversal agent and departure from the operation room. We a priori restricted our analysis to side effects requiring pharmacologic treatment that were therefore presumably clinically meaningful. Sugammadex would be considered noninferior to neostigmine (or vice versa) if the odds ratio for composite of side effects did not exceed 1.2. RESULTS: Among 89,753 surgeries in 70,690 patients, 16,480 (18%) were given sugammadex and 73,273 (82%) were given neostigmine. The incidence of composite outcome was 3.4% in patients given sugammadex and 3.0% in patients given neostigmine. The most common individual side effect was bradycardia (2.4% in the sugammadex group versus 2.2% neostigmine). Noninferiority was not found, with an estimated odds ratio of 1.21 (sugammadex versus neostigmine; 95% confidence interval [CI], 1.09-1.34; noninferiority P = .57), and neostigmine was superior to sugammadex with an estimated odds ratio of 0.83 (0.74-0.92), 1-side superiority P < .001. CONCLUSIONS: The composite incidence was less with neostigmine than with sugammadex, but only by 0.4% (a negligible clinical effect). Since 250 patients would need to be given neostigmine rather than sugammadex to avoid 1 episode of a minor complication such as bradycardia or bronchospasm, we conclude that sugammadex and neostigmine are comparably safe.

Required dose of sugammadex or neostigmine for reversal of vecuronium-induced shallow residual neuromuscular block at a train-of-four ratio of 0.3.

Residual shallow neuromuscular block (NMB) is potentially harmful and contributes to critical respiratory events. Evidence for the optimal dose of sugammadex required to reverse vecuronium-induced shallow NMB is scarce. The aims of the present study were to find suitable doses of sugammadex and neostigmine to reverse a residual vecuronium-induced NMB from a time of flight (TOF) ratio of 0.3-0.9 and evaluate their safety and efficacy. In total, 121 patients aged 18-65 years were randomly assigned to 11 groups to receive placebo, sugammadex (doses of 0.125, 0.25, 0.5, 1.0, or 2.0 mg/kg), or neostigmine (doses of 10, 25, 40, 55, or 70 µg/kg). The reversal time of sugammadex and neostigmine to antagonize a vecuronium-induced shallow residual NMB (i.e., TOF ratio of 0.3) and related adverse reactions were recorded. Several statistical models were tested to find an appropriate statistical model to explore the suitable doses of sugammadex and neostigmine required to reverse a residual vecuronium-induced NMB. Based on a monoexponential model with the response variable on a logarithmic scale, sugammadex 0.56 mg/kg may be sufficient to reverse vecuronium-induced shallow residual NMB at a TOF ratio of 0.3 under anesthesia maintained with propofol. Neostigmine may not provide prompt and satisfactory antagonism as sugammadex, even in shallow NMB.

Epidemiology and outcomes of residual neuromuscular blockade: A systematic review of observational studies.

OBJECTIVES: Complete reversal of neuromuscular blockade (NMB) is important for patient safety and prognosis following surgical procedures involving NMB agents (NMBAs). Published evidence on the epidemiology and consequences of residual neuromuscular blockade (rNMB; incomplete neuromuscular recovery) in real-world clinical settings is lacking with advances in NMB management. Therefore, we aimed to examine the burden of rNMB and its associated clinical, economic and humanistic outcomes using a systematic review framework. REVIEW METHODS: Electronic and conference database searches were performed to include observational studies examining rNMB or related outcomes in adults undergoing surgery and receiving NMBAs with or without NMBA antagonists. RESULTS: Of 1438 screened abstracts, 58 studies with 25,277 total patients were included. Inconsistent definitions of rNMB were reported across studies with 44 (76%) and 29 (50%) studies utilizing quantitative and qualitative measures to detect rNMB, respectively. The most common definition of rNMB was train-of-four ratio (TOFR) <0.9 (29 studies) and TOFR <0.7 (16 studies) measured at post-anesthesia care unit (PACU) entry. For TOFR <0.9 at PACU entry, rNMB incidence ranged from 0% to 90.5% (median 30%) overall; 0% to 16.0% in the sugammadex (SUG) group; 3.5% to 90.5% in the neostigmine (NEO) group; and 15% to 89% in the spontaneous recovery (SR) group. Twenty-one studies reported clinical outcomes (reintubation, mild hypoxemia, or a respiratory event) or resource utilization outcomes (hospital/PACU length of stay [LOS]) by presence/absence of rNMB. Patients with rNMB had higher rates of acute respiratory events compared to those without rNMB. CONCLUSIONS: Real-world observational studies show a significant burden of rNMB and associated health sequelae, though rNMB measures were not reported consistently across studies. Appropriate quantitative measurement is needed to accurately identify rNMB, and interventions are needed to reduce its burden and associated adverse outcomes.

Postoperative residual neuromuscular blockade after reversal based on a qualitative peripheral nerve stimulator response: A randomised controlled trial.

BACKGROUND: Incomplete recovery of neuromuscular blockade is a common postoperative adverse event in the postanaesthesia care unit. OBJECTIVE: We examined and compared the incidence of residual neuromuscular blockade when the recommended dose of neostigmine or sugammadex was administered according to a qualitative nerve stimulator response. DESIGN: A randomised controlled trial. SETTING: A tertiary care hospital in South Korea from September 2017 to November 2017. PATIENTS: Eighty patients aged between 18 and 69 years were included in this study. All were patients scheduled to undergo elective laparoscopic cholecystectomy and who had an American Society of Anaesthesiologists physical status of one or two were eligible. INTERVENTIONS: Patients were allocated randomly to receive neostigmine or sugammadex at the end of surgery. The doses of the reversal agents were based on the response to peripheral nerve stimulation, which was discontinued after administration of the reversal agent. MAIN OUTCOME MEASURES: The primary outcome was the incidence of postoperative residual neuromuscular blockade. The secondary outcomes were the incidences of symptoms or signs of residual neuromuscular blockade such as hypoxaemia, inability to maintain head-lift for 5 s and diplopia. RESULTS: The incidence of residual neuromuscular blockade on arrival in the recovery room was 44.4% in the neostigmine group and 0% in the sugammadex group (P < 0.0001, relative risk = 1.80, 95% confidence interval 1.36 to 2.41). The incidences of adverse events in the recovery room were low and comparable between the groups. CONCLUSION: The incidence of residual neuromuscular blockade on arrival in the recovery room was significantly higher in the neostigmine group than that in the sugammadex group. However, the incidence of adverse events was similar in the neostigmine and sugammadex groups. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03292965.

Anesthesiologists' Overconfidence in Their Perceived Knowledge of Neuromuscular Monitoring and Its Relevance to All Aspects of Medical Practice: An International Survey.

BACKGROUND: In patients who receive a nondepolarizing neuromuscular blocking drug (NMBD) during anesthesia, undetected postoperative residual neuromuscular block is a common occurrence that carries a risk of potentially serious adverse events, particularly postoperative pulmonary complications. There is abundant evidence that residual block can be prevented when real-time (quantitative) neuromuscular monitoring with measurement of the train-of-four ratio is used to guide NMBD administration and reversal. Nevertheless, a significant percentage of anesthesiologists fail to use quantitative devices or even conventional peripheral nerve stimulators routinely. Our hypothesis was that a contributing factor to the nonutilization of neuromuscular monitoring was anesthesiologists' overconfidence in their knowledge and ability to manage the use of NMBDs without such guidance. METHODS: We conducted an Internet-based multilingual survey among anesthesiologists worldwide. We asked respondents to answer 9 true/false questions related to the use of neuromuscular blocking drugs. Participants were also asked to rate their confidence in the accuracy of each of their answers on a scale of 50% (pure guess) to 100% (certain of answer). RESULTS: Two thousand five hundred sixty persons accessed the website; of these, 1629 anesthesiologists from 80 countries completed the 9-question survey. The respondents correctly answered only 57% of the questions. In contrast, the mean confidence exhibited by the respondents was 84%, which was significantly greater than their accuracy. Of the 1629 respondents, 1496 (92%) were overconfident. CONCLUSIONS: The anesthesiologists surveyed expressed overconfidence in their knowledge and ability to manage the use of NMBDs. This overconfidence may be partially responsible for the failure to adopt routine perioperative neuromuscular monitoring. When clinicians are highly confident in their knowledge about a procedure, they are less likely to modify their clinical practice or seek further guidance on its use.

Effectiveness of sugammadex versus neostigmine on restoration of neuromuscular function in surgical patients with myasthenia gravis undergoing rocuronium-induced neuromuscular blockade: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this systematic review is to identify the effectiveness of sugammadex versus neostigmine on the reversal of rocuronium-induced neuromuscular blockade in surgical patients with myasthenia gravis undergoing general anesthesia.

Delineating the Trajectory of Cognitive Recovery From General Anesthesia in Older Adults: Design and Rationale of the TORIE (Trajectory of Recovery in the Elderly) Project.

BACKGROUND: Mechanistic aspects of cognitive recovery after anesthesia and surgery are not yet well characterized, but may be vital to distinguishing the contributions of anesthesia and surgery in cognitive complications common in the elderly such as delirium and postoperative cognitive dysfunction. This article describes the aims and methodological approach to the ongoing study, Trajectory of Recovery in the Elderly (TORIE), which focuses on the trajectory of cognitive recovery from general anesthesia. METHODS: The study design employs cognitive testing coupled with neuroimaging techniques such as functional magnetic resonance imaging, diffusion tensor imaging, and arterial spin labeling to characterize cognitive recovery from anesthesia and its biological correlates. Applying these techniques to a cohort of age-specified healthy volunteers 40-80 years of age, who are exposed to general anesthesia alone, in the absence of surgery, will assess cognitive and functional neural network recovery after anesthesia. Imaging data are acquired before, during, and immediately after anesthesia, as well as 1 and 7 days after. Detailed cognitive data are captured at the same time points as well as 30 days after anesthesia, and brief cognitive assessments are repeated at 6 and 12 months after anesthesia. RESULTS: The study is underway. Our primary hypothesis is that older adults may require significantly longer to achieve cognitive recovery, measured by Postoperative Quality of Recovery Scale cognitive domain, than younger adults in the immediate postanesthesia period, but all will fully recover to baseline levels within 30 days of anesthesia exposure. Imaging data will address systems neuroscience correlates of cognitive recovery from general anesthesia. CONCLUSIONS: The data acquired in this project will have both clinical and theoretical relevance regardless of the outcome by delineating the mechanism behind short-term recovery across the adult age lifespan, which will have major implications for our understanding of the effects of anesthetic drugs.

Neostigmine-based reversal of intermediate acting neuromuscular blocking agents to prevent postoperative residual paralysis: A systematic review.

BACKGROUND: Neostigmine is widely used to antagonise residual paralysis. Over the last decades, the benchmark of acceptable neuromuscular recovery has increased progressively to a train-of-four (TOF) ratio of at least 0.9. Raising this benchmark may impact on the efficacy of neostigmine. OBJECTIVE(S): The systematic review evaluates the efficacy of neostigmine to antagonise neuromuscular block to attain a TOF ratio of at least 0.9. DESIGN: We performed a systematic search of the literature from January 1992 to December 2015. DATA SOURCES OR SETTING: PubMed, EMBASE and the Cochrane Controlled Clinical Trials database were searched for randomised controlled human studies. Search was performed without language restrictions, using the following free text terms: 'neostigmine', 'sugammadex', 'edrophonium' or 'pyridostigmine' AND 'neuromuscular block', 'reversal' or 'reverse'. ELIGIBILITY CRITERIA: Studies were accepted for inclusion if they used quantitative neuromuscular monitoring and neostigmine as the reversal agent. Selected trials were checked by two of the authors for data integrity. Trials relevant for inclusion had to report the number of patients included, the type of anaesthetic maintenance, the type of neuromuscular blocking agent used, the reversal agent and dose used, the depth of neuromuscular block when neostigmine was administered and the reversal time (time from injection of neostigmine until a TOF ratio ≥0.9 was attained). RESULTS: 19 trials were eligible for quantitative analysis. In patients with deep residual block [T1 (first twitch height) <10%] 70 µg kg neostigmine was used (five trials, 118 patients), and the mean reversal time was 17.1 min (95% confidence interval (CI) [12.4 to 21.8]). In patients with moderate residual block (T1 10% to <25%) the mean neostigmine dose was 56 µg kg (seven trials, 342 patients), and the mean reversal time was 11.3 min (95% CI [9.2 to 13.4]). In patients with a shallow residual block (T1 ≥ 25%) the mean neostigmine dose was 40 µg kg (13 trials, 535 patients), and the mean reversal time was 8.0 min (95% CI [6.8 to 9.2]). CONCLUSION: Based on the findings of this systematic review, we recommend that the administration of neostigmine be delayed until an advanced degree of prereversal recovery has occurred (i.e. a T1 >25% of baseline), or that a recovery time longer than 15 min be accepted.

Preparing for the unexpected: special considerations and complications after sugammadex administration.

Sugammadex, a modified gamma-cyclodextrin, has changed clinical practice of neuromuscular reversal dramatically. With the introduction of this selective relaxant binding agent, rapid and reliable neuromuscular reversal from any depth of block became possible. Sugammadex can reverse neuromuscular blockade without the muscarinic side effects typically associated with the administration of acetylcholinesterase inhibitors. However, what remained unchanged is the incidence of residual neuromuscular blockade. It is known that sugammadex cannot always prevent its occurrence, if appropriate dosing is not chosen based on the level of neuromuscular paralysis prior to administration determined by objective neuromuscular monitoring. Alternatively, excessive doses of sugammadex administered in an attempt to ensure full and sustained reversal may affect the effectiveness of rocuronium in case of immediate reoperation or reintubation. In such emergent scenarios that require onset of rapid and reliable neuromuscular blockade, the summary of product characteristics (package insert) recommends using benzylisoquinolinium neuromuscular blocking agents or a depolarizing agent. However, if rapid intubation is required, succinylcholine has a significant number of side effects, and benzylisoquinolinium agents may not have the rapid onset required. Therefore, prior administration of sugammadex introduces a new set of potential problems that require new solutions. This novel reversal agent thus presents new challenges and anesthesiologists must familiarize themselves with specific issues with its use (e.g., bleeding risk, hypermagnesemia, hypothermia). This review will address sugammadex administration in such special clinical situations.

Effects of calcium chloride coadministered with neostigmine on neuromuscular blockade recovery: A double-blind randomised study.

BACKGROUND: Ionised calcium plays an important role in neuromuscular transmission, but its effects on the reversal of nondepolarising neuromuscular blockade have not been fully evaluated. OBJECTIVE: We examined whether calcium chloride coadministered with neostigmine could enhance the rate of neuromuscular recovery. DESIGN: Randomised double-blind trial. SETTING: A tertiary teaching hospital. PATIENTS: In total, 53 patients undergoing elective surgery under general anaesthesia with neuromuscular monitoring by acceleromyography using a TOF-Watch SX monitor. INTERVENTIONS: Patients were randomly allocated to receive either 5 mg kg of calcium chloride (calcium group, n = 26) or the same volume of normal saline (control group, n = 27) coadministered with 25 µg kg of neostigmine and 15 µg kg of atropine at the end of surgery. MAIN OUTCOME MEASURES: The primary end point was the neuromuscular recovery time [time from neostigmine administration to recovery of the TOF ratio (TOFr) to 0.9]. Secondary end points included the TOFr at 5, 10 and 20 min after neostigmine administration and the incidence of postoperative residual curarisation (PORC), defined as a TOFr less than 0.9 at each time point. RESULTS: The neuromuscular recovery time was significantly faster in the calcium group than in the control group (median [Q1 to Q3]; 5.0 [3.0 to 7.0] vs. 6.7 [5.7 to 10.0] min, respectively; P = 0.007). At 5 min after neostigmine administration, the TOFr was higher [87 (74 to 100) vs. 68 (51 to 81)%, respectively; P = 0.002] and the incidence of PORC was lower (50.0 vs. 81.5%, respectively; P = 0.016) in the calcium group than in the control group. There were no differences between the two groups with respect to the TOFr or incidence of PORC at 10 and 20 min after neostigmine administration. CONCLUSION: Calcium chloride coadministered with neostigmine enhanced neuromuscular recovery in the early period of nondepolarising neuromuscular blockade reversal.

Impact of reversal strategies on the incidence of postoperative residual paralysis after rocuronium relaxation without neuromuscular monitoring: A partially randomised placebo controlled trial.

BACKGROUND: Electronic neuromuscular monitoring is not widely used to determine either the reversal requirements for neuromuscular block before extubation of the trachea, or to determine if there is any subsequent postoperative residual neuromuscular block (PORNB). OBJECTIVES: To investigate the incidence of PORNB using acceleromyography after spontaneous recovery of rocuronium-induced block and to compare this with the administration of sugammadex, neostigmine or a placebo. DESIGN: Partially randomised, partially randomised, placebo-controlled, double-blind, four-group parallel-arm study. SETTING: Single-centre study performed between October 2013 and December 2015 in a university hospital. PATIENTS: Of the 134 eligible patients, 128 gave their consent and 125 of these completed the study. INTERVENTIONS: Patients received general anaesthesia with propofol, sevoflurane, fentanyl and rocuronium. Neuromuscular transmission was measured by acceleromyography (TOF-Watch-SX; Organon Teknika B.V., Boxtel, the Netherlands) but the anaesthetist was blind to the results. If the anaesthetist deemed pharmacological reversal to be necessary before extubation of the trachea then patients were assigned randomly to receive either sugammadex (2.0 mg kg), neostigmine (0.05 mg kg) or a placebo. In the postanaesthesia care unit, an independent anaesthetist, unaware of the treatment given, assessed the neuromuscular function using acceleromyography. MAIN OUTCOME MEASURES: The incidence of a normalised train-of-four ratio less than 0.9 on arrival in the recovery room. RESULTS: In total, 125 patients were recruited. Neuromuscular block was allowed to recover spontaneously in 50 patients, whereas the remainder received either sugammadex (27), neostigmine (26) or placebo (22). The number of cases with PORNB were one (3.7%), four (15%), 13 (26%) and 10 (45%) after sugammadex, neostigmine, spontaneous recovery and placebo, respectively. Sugammadex and neostigmine were more effective than placebo [odds ratio (OR): 0.05, 95% confidence interval (CI): 0.005 to 0.403, P = 0.005; OR: 0.22, 95% CI: 0.056 to 0.85, P = 0.028, respectively]. Sugammadex performed better than spontaneous recovery (OR: 0.11, 95% CI: 0.014 to 0.89, P = 0.039) unlike neostigmine (OR: 0.52, 95% CI: 0.15 to 1.79, P = 0.297). Yet, antagonism (pooled data) was more effective than spontaneous recovery (OR: 0.3, 95% CI: 0.1 to 0.9, P = 0.03). CONCLUSION: Although pharmacological reversal based on clinical signs was superior to spontaneous recovery it did not prevent PORNB, irrespective of the reversal agent. TRIAL REGISTRATION: The study is registered under EUDRACT number 2013-001965-17.

Cisatracurium- and rocuronium-associated residual neuromuscular dysfunction under intraoperative neuromuscular monitoring and postoperative neostigmine reversal: a single-blind randomized trial.

BACKGROUND: Postoperative residual neuromuscular blockade (RNMB) is a common complication in the postanesthesia care unit (PACU), but also one of the most controversial issues. Many studies and trials demonstrated that some methods and techniques can reduce the incidence and the extent of the phenomenon. STUDY OBJECTIVE: To determine the incidence of RNMB in the PACU at standardized times after extubation with the implementation of a protocol of careful neuromuscular blockade management. DESIGN: Randomized, single-blinded controlled clinical trial. SETTING: Operating room and PACU. PATIENTS: A total of 120 patients of either sex with American Society of Anesthesiologists grades 1, 2, and 3, aged 18 to 80 years were scheduled to undergo elective abdominal surgical procedures lasting for at least 60 minutes. INTERVENTIONS: Patients were randomized to receive either cisatracurium (n=60) or rocuronium (n=60) at the time of intubation and during surgery. Every patient received quantitative neuromuscular monitoring during general anesthesia. On completion of surgery, patients were given neostigmine 0.05 mg kg-1. Patients were extubated at a train-of-four (TOF) ratio≥0.9. MEASUREMENTS: TOF measurements were performed 15, 30, and 60 minutes after extubation. Tolerability of neuromuscular monitoring was evaluated with a scale from 1 to 10 (with 1 meaning no discomfort at all and 10 meaning maximal discomfort or pain). RESULTS: Six, 11, and 14 patients (5.0%, 9.2%, and 11.7%) exhibited a TOF ratio <0.9 at 15, 30, and 60 minutes after extubation, respectively. No statistically significant difference in the postoperative RNMB between cisatracurium and rocuronium was found. The median tolerability score for neuromuscular monitoring was 3. CONCLUSION: Careful conduction, monitoring, and subsequent reversal of neuromuscular block may allow for obtaining considerably low incidence of residual neuromuscular block. However, our trial shows that some mid- and long-term cases of TOF ratios <0.9 can still occur, possibly jeopardizing the patients' postoperative recovery.