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      Reevaluation and update on efficacy and safety of neostigmine for reversal of neuromuscular blockade

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          Abstract

          Postoperative residual neuromuscular block is a serious threat which endangers the patient safety. Neostigmine has been the most commonly used anticholinesterase for the pharmacological reversal of neuromuscular blockade. Although newer agents have been introduced recently, neostigmine has some irreplaceable advantages, including broad-spectrum reversal of all nondepolarizing neuromuscular blocking drugs, low cost, and availability of more related data for clinical practice to refer to. Neostigmine is also noticed to have some drawbacks, such as the inability to reverse profound and deep blockade, potential induction of muscle weakness, cardiovascular adverse effects, and so on. Data on the usage of neostigmine in the geriatric and the pediatric population are still insufficient. Some discrepancies are observed in the results from previous studies which need further investigation. However, recent studies offer some renewed information. Regarding both efficacy and safety, the key for successful reversal of neuromuscular blockade is to use neostigmine “appropriately,” optimizing the dosage and timing of administration under close monitoring.

          Most cited references92

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          Efficacy and safety of sugammadex versus neostigmine in reversing neuromuscular blockade in adults.

          Acetylcholinesterase inhibitors, such as neostigmine, have traditionally been used for reversal of non-depolarizing neuromuscular blocking agents. However, these drugs have significant limitations, such as indirect mechanisms of reversal, limited and unpredictable efficacy, and undesirable autonomic responses. Sugammadex is a selective relaxant-binding agent specifically developed for rapid reversal of non-depolarizing neuromuscular blockade induced by rocuronium. Its potential clinical benefits include fast and predictable reversal of any degree of block, increased patient safety, reduced incidence of residual block on recovery, and more efficient use of healthcare resources.
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            Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study

            Objective To determine whether use of intermediate acting neuromuscular blocking agents during general anesthesia increases the incidence of postoperative respiratory complications. Design Prospective, propensity score matched cohort study. Setting General teaching hospital in Boston, Massachusetts, United States, 2006-10. Participants 18 579 surgical patients who received intermediate acting neuromuscular blocking agents during surgery were matched by propensity score to 18 579 reference patients who did not receive such agents. Main outcome measures The main outcome measures were oxygen desaturation after extubation (hemoglobin oxygen saturation 3%) and reintubations requiring unplanned admission to an intensive care unit within seven days of surgery. We also evaluated effects on these outcome variables of qualitative monitoring of neuromuscular transmission (train-of-four ratio) and reversal of neuromuscular blockade with neostigmine to prevent residual postoperative neuromuscular blockade. Results The use of intermediate acting neuromuscular blocking agents was associated with an increased risk of postoperative desaturation less than 90% after extubation (odds ratio 1.36, 95% confidence interval 1.23 to 1.51) and reintubation requiring unplanned admission to an intensive care unit (1.40, 1.09 to 1.80). Qualitative monitoring of neuromuscular transmission did not decrease this risk and neostigmine reversal increased the risk of postoperative desaturation to values less than 90% (1.32, 1.20 to 1.46) and reintubation (1.76, 1.38 to 2.26). Conclusion The use of intermediate acting neuromuscular blocking agents during anesthesia was associated with an increased risk of clinically meaningful respiratory complications. Our data suggest that the strategies used in our trial to prevent residual postoperative neuromuscular blockade should be revisited.
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              Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action.

              Residual neuromuscular blockade remains a problem even after short surgical procedures. The train-of-four (TOF) ratio at the adductor pollicis required to avoid residual paralysis is now considered to be at least 0.9. The incidence of residual paralysis using this new threshold is not known, especially after a single intubating dose of intermediate-duration nondepolarizing relaxant. Therefore, the aim of the study was to determine the incidence of residual paralysis in the postanesthesia care unit after a single intubating dose of twice the ED(95) of a nondepolarizing muscle relaxant with an intermediate duration of action. Five hundred twenty-six patients were enrolled. They received a single dose of vecuronium, rocuronium, or atracurium to facilitate tracheal intubation and received no more relaxant thereafter. Neuromuscular blockade was not reversed at the end of the procedure. On arrival in the postanesthesia care unit, the TOF ratio was measured at the adductor pollicis, using acceleromyography. Head lift, tongue depressor test, and manual assessment of TOF and DBS fade were also performed. The time delay between the injection of muscle relaxant and quantitative measurement of neuromuscular blockade was calculated from computerized anesthetic records. The TOF ratios less than 0.7 and 0.9 were observed in 16% and 45% of the patients, respectively. Two hundred thirty-nine patients were tested 2 h or more after the administration of the muscle relaxant. Ten percent of these patients had a TOF ratio less than 0.7, and 37% had a TOF ratio less than 0.9. Clinical tests (head lift and tongue depressor) and manual assessment of fade showed a poor sensitivity (11-14%) to detect residual blockade (TOF < 0.9). After a single dose of intermediate-duration muscle relaxant and no reversal, residual paralysis is common, even more than 2 h after the administration of muscle relaxant. Quantitative measurement of neuromuscular transmission is the only recommended method to diagnose residual block.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2018
                10 December 2018
                : 14
                : 2397-2406
                Affiliations
                Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China, ms89011068@ 123456163.com
                Author notes
                Correspondence: Su Min, Department of Anesthesiology, The First Affiliated Hospital of Chongqing Medical University, No 1 Youyi Road, Yuzhong District, Chongqing 400016, China, Tel/fax +86 23 8901 1068, Email ms89011068@ 123456163.com
                Article
                tcrm-14-2397
                10.2147/TCRM.S179420
                6292224
                30573962
                dc6df5d3-87b5-43d8-881f-ad408cc97506
                © 2018 Luo et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Review

                Medicine
                postoperative residual neuromuscular block,neuromuscular reversal,anticholin-esterase,postanesthesia care,postoperative complication

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