Effect of Reversal of Neuromuscular Blockade with Sugammadex versus Usual Care on Bleeding Risk in a Randomized Study of Surgical Patients
Niels Rahe‐MeyerHein FennemaSam SchulmanWalter KlimschaMichael PrzemeckManfred BlobnerHinnerk WulfMarcel SpeekChristine McCrary SiskDebora Williams‐HermanTiffany WooArmin Szegedi
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Previous studies show a prolongation of activated partial thromboplastin time and prothrombin time in healthy volunteers after treatment with sugammadex. The authors investigated the effect of sugammadex on postsurgical bleeding and coagulation variables.This randomized, double-blind trial enrolled patients receiving thromboprophylaxis and undergoing hip or knee joint replacement or hip fracture surgery. Patients received sugammadex 4 mg/kg or usual care (neostigmine or spontaneous recovery) for reversal of rocuronium- or vecuronium-induced neuromuscular blockade. The Cochran-Mantel-Haenszel method, stratified by thromboprophylaxis and renal status, was used to estimate relative risk and 95% confidence interval (CI) of bleeding events with sugammadex versus usual care. Safety was further evaluated by prespecified endpoints and adverse event reporting.Of 1,198 patients randomized, 1,184 were treated (sugammadex n = 596, usual care n = 588). Bleeding events within 24 h (classified by an independent, blinded Adjudication Committee) were reported in 17 (2.9%) sugammadex and 24 (4.1%) usual care patients (relative risk [95% CI], 0.70 [0.38 to 1.29]). Compared with usual care, increases of 5.5% in activated partial thromboplastin time (P < 0.001) and 3.0% in prothrombin time (P < 0.001) from baseline with sugammadex occurred 10 min after administration and resolved within 60 min. There were no significant differences between sugammadex and usual care for other blood loss measures (transfusion, 24-h drain volume, drop in hemoglobin, and anemia), or risk of venous thromboembolism, and no cases of anaphylaxis.Sugammadex produced limited, transient (<1 h) increases in activated partial thromboplastin time and prothrombin time but was not associated with increased risk of bleeding versus usual care.Keywords:
Sugammadex
Prothrombin time
Sugammadex
Neuromuscular monitoring
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Background Sugammadex selectively binds steroidal neuromuscular blocking drugs, leading to reversal of neuromuscular blockade. The authors developed a pharmacokinetic-pharmacodynamic model for reversal of neuromuscular blockade by sugammadex, assuming that reversal results from a decrease of free drug in plasma and/or neuromuscular junction. The model was applied for predicting the interaction between sugammadex and rocuronium or vecuronium. Methods Noninstantaneous equilibrium of rocuronium-sugammadex complex formation was assumed in the pharmacokinetic-pharmacodynamic interaction model. The pharmacokinetic parameters for the complex and sugammadex alone were assumed to be identical. After development of a pharmacokinetic-pharmacodynamic model for rocuronium alone, the interaction model was optimized using rocuronium and sugammadex concentration data after administration of 0.1-8 mg/kg sugammadex 3 min after administration of 0.6 mg/kg rocuronium. Subsequently, the predicted reversal of neuromuscular blockade by sugammadex was compared with data after administration of up to 8 mg/kg sugammadex at reappearance of second twitch of the train-of-four; or 3, 5, or 15 min after administration of 0.6 mg/kg rocuronium. Finally, the model was applied to predict reversal of vecuronium-induced neuromuscular blockade. Results Using the in vitro dissociation constants for the binding of rocuronium and vecuronium to sugammadex, the pharmacokinetic-pharmacodynamic interaction model adequately predicted the increase in total rocuronium and vecuronium plasma concentrations and the time-course of reversal of neuromuscular blockade. Conclusions Model-based evaluation supports the hypothesis that reversal of rocuronium- and vecuronium-induced neuromuscular blockade by sugammadex results from a decrease in the free rocuronium and vecuronium concentration in plasma and neuromuscular junction. The model is useful for prediction of reversal of rocuronium and vecuronium-induced neuromuscular blockade with sugammadex.
Sugammadex
Pharmacodynamics
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Survey of Anesthesiology: June 2008 - Volume 52 - Issue 3 - p 138-139 doi: 10.1097/SA.0b013e318179f0ef
Sugammadex
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(Abstracted from J Clin Anesth, 35:497–501, 2016) Sugammadex is a selective muscle relaxant binding agent with a γ-cyclodextrin structure, which reverses rocuronium- and vecuronium-induced neuromuscular blockade by chemical encapsulation. The objective of this retrospective, observational study was to evaluate the efficacy and safety of sugammadex for the reversal of profound neuromuscular blockade by rocuronium in infant patients.
Sugammadex
Muscle relaxant
Rocuronium Bromide
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Duvaldestin, P.; Kuizenga, K.; Kjaer, C C.; Saldien, V.; Debaene, B. Author Information
Sugammadex
Vecuronium bromide
Neuromuscular monitoring
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Survey of Anesthesiology: February 2010 - Volume 54 - Issue 1 - p 39 doi: 10.1097/SA.0b013e3181caed2c
Sugammadex
Neuromuscular monitoring
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Sugammadex
Neuromuscular monitoring
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Background: Sugammadex is a new reversal agent for nondepolarizing neuromuscular blockade. We conducted the randomized clinical study to compare the recovery between sugammadex alone and combined use of sugammadex and neostigmine.
Methods: Forty adult patients were randomly allocated to Group S (n=20) or Group SN (n=20). General anesthesia was induced and maintained with propofol and remifentanil. The patients were intubated without neuromuscular blockers. After the stabilization of TOF Watch SX® acceleromyography as control, rocuronium 0.6 mg/kg was administered to patients in both groups. The patients in Group S received sugammadex 1.0 mg/kg and those in Group SN received sugammadex 0.5 mg/kg, neostigmine 0.04 mg/kg and atropine 0.02 mg/kg five minutes after rocuronium administration. The cost of reversal and recovery time were measured in both groups.
Results: We analyzed the data of 36 patients (n=18 in each group). The T1/control ratios were significantly higher in Group SN than in group S at 5, 10 and 15minutes after administration of reversal agents. The TOF ratios were significantly higher in Group SN than in group S at 10 and 15minutes after administration of reversal agents. The 90% recovery time of TOF ratio in Group SN was significantly shorter than that in Group S. The cost of reversal was significantly smaller in Group SN than in Group S.
Conclusions: By partially substituting sugammadex with neostigmine, we can attain faster recovery from rocuronium-induced profound neuromuscular blockade.
Sugammadex
Rocuronium Bromide
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University Department of Anaesthesia, Royal Liverpool University Hospital, Liverpool, United Kingdom
Sugammadex
Neuromuscular monitoring
Rocuronium Bromide
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Sugammadex reversiert die Wirkung von Rocuronium durch Enkapsulierung ohne muskarinerge Nebenwirkungen. Bisherige publizierte Studien zeigen eine effektive dosisabhängige Reversierung der neuromuskulären Blockade nach Verwendung von Rocuronium oder Vecuronium. Wir berichten in unserem Fallbericht von einem Patienten, der am Ende der OP nach RSI mit Rocuronium eine tiefe neuromuskuläre Blockade zeigte, die innerhalb weniger Minuten nebenwirkungsfrei reversiert werden konnte.
Sugammadex
Rapid sequence induction
Continuous Infusion
Muscle relaxation
Neuromuscular monitoring
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