Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects

BMC Anesthesiology

Xinmin Wu⁷  Helle Oerding⁵  Jin Liu⁹  Bernard Vanacker¹²  Shanglong Yao³  Vegard Dahl¹¹  Lize Xiong⁶  Casper Claudius²  Yun Yue¹  Yuguang Huang⁸  Esther Abels⁴  Henk Rietbergen⁴  Tiffany Woo¹⁰ 

[1] Beijing Chaoyang Hospital, Beijing, China

[2] Department of Anaesthesia, Hillerød Hospital, Hillerød, Denmark

[3] Union Hospital, Tongji Medical College, Wuhan, China

[4] MSD, Oss, The Netherlands

[5] Department of Anaesthesiology, Vejle Hospital, Vejle, Denmark

[6] Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, China

[7] Peking University First Hospital, No 8 Xishiku St, Beijing 100034, China

[8] Peking Union Medical College Hospital, Beijing, China

[9] West China Hospital, Sichuan University, Chengdu, China

[10] Merck Sharp & Dohme Corp, Whitehouse Station, NJ, USA

[11] Anaesthesia and Intensive Care, Asker and Baerum Hospital, Oslo, Norway

[12] Department of Anesthesiology, University Hospitals Leuven, Leuven, Belgium

关键词: Caucasian;    Chinese;    Neuromuscular blockade;    Neostigmine;    Rocuronium;    Sugammadex;   

Others  :  1084691
DOI  :  10.1186/1471-2253-14-53

 received in 2014-01-17, accepted in 2014-06-26,  发布年份 2014

【 摘 要 】

Background

This study compared efficacy and safety of the selective relaxant binding agent sugammadex (2 mg/kg) with neostigmine (50 μg/kg) for neuromuscular blockade (NMB) reversal in Chinese and Caucasian subjects.

Methods

This was a randomized, active-controlled, multicenter, safety-assessor-blinded study (NCT00825812) in American Society of Anesthesiologists Class 1-3 subjects undergoing surgery with propofol anesthesia. Rocuronium 0.6 mg/kg was administered for endotracheal intubation, with 0.1–0.2 mg/kg maintenance doses given as required. NMB was monitored using TOF-Watch^® SX. At second twitch reappearance, after last rocuronium dose, subjects received sugammadex 2 mg/kg or neostigmine 50 μg/kg plus atropine 10–20 μg/kg, according to randomization. Primary efficacy variable was time from sugammadex/neostigmine to recovery of the train-of-four (TOF) ratio to 0.9.

Results

Overall, 230 Chinese subjects (sugammadex, n = 119, neostigmine, n = 111); and 59 Caucasian subjects (sugammadex, n = 29, neostigmine, n = 30) had evaluable data. Geometric mean (95% CI) time to recovery to TOF ratio 0.9 was 1.6 (1.5–1.7) min with sugammadex vs 9.1 (8.0–10.3) min with neostigmine in Chinese subjects. Corresponding times for Caucasian subjects were 1.4 (1.3–1.5) min and 6.7 (5.5–8.0) min, respectively. Sugammadex 2 mg/kg was generally well tolerated, with no serious adverse events reported. There was no residual NMB or recurrence of NMB.

Conclusion

Both Chinese and Caucasian subjects recovered from NMB significantly faster after sugammadex 2 mg/kg vs neostigmine 50 μg/kg, with a ~5.7 times (p < 0.0001) faster recovery with sugammadex vs neostigmine in Chinese subjects. Sugammadex was generally well tolerated.

Trial registration

ClinicalTrials.gov Identifier: NCT00825812.

【 授权许可】

   
2014 Wu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

【 参考文献 】

• [1]Tramer MR, Fuchs-Buder T: Omitting antagonism of neuromuscular block: effect on postoperative nausea and vomiting and risk of residual paralysis. a systematic review. Br J Anaesth 1999, 82:379-386.
• [2]Murphy GS, Szokol JW, Marymont JH, Greenberg SB, Avram MJ, Vender JS: Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit. Anesth Analg 2008, 107:130-137.
• [3]Blobner M, Eriksson LI, Scholz J, Motsch J, Della Rocca G, Prins ME: Reversal of rocuronium-induced neuromuscular blockade with sugammadex compared with neostigmine during sevoflurane anaesthesia: results of a randomised, controlled trial. Eur J Anaesthesiol 2010, 27:874-881.
• [4]Booij LHDJ, de Boer HD, van Egmond J: Reversal agents for nondepolarizing neuromuscular blockade: reasons for and development of a new concept. Semin Anesth Periop Med Pain 2002, 32:92-98.
• [5]Saarnivaara L, Simila M: Effects of four anticholinesterase-anticholinergic combinations and tracheal extubation on QTc interval of the ECG, heart rate and arterial pressure. Acta Anaethesiol Scand 1998, 42:460-463.
• [6]Vanacker BF, Vermeyen KM, Struys MM, Rietbergen H, Vandermeersch E, Saldien V, Kalmar AF, Prins ME: Reversal of rocuronium induced neuromuscular block with the novel drug sugammadex is equally effective under maintenance anaesthesia with propofol or sevoflurane. Anaesth Analg 2007, 104:563-568.
• [7]Khuenl-Brady KS, Wattwil M, Vanacker BF, Lora-Tamayo JI, Rietbergen H, Alvarez-Gomez JA: Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial. Anesth Analg 2010, 110:64-73.
• [8]Fuchs-Buder T, Claudius C, Skovgaard LT, Eriksson LI, Mirakhur RK, Viby-Mogensen J, 8th International Neuromuscular Meeting: Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand 2007, 51:789-808.
• [9]Claudius C, Viby-Mogensen J: Acceleromyography for use in scientific and clinical practice: a systematic review of the evidence. Anesthesiology 2008, 108:1117-1140.
• [10]Apfel CC, Läärä E, Koivuranta M, Greim CA, Roewer N: Simplified risks score for predicting postoperative nausea and vomiting: conclusions from cross-validations between two centers. Anesthesiology 1999, 91:693-700.
• [11]Sorgenfrei I, Norrild K, Larsen P, Stensballe J, Ostergaard D, Prins M, Viby-Mogensen J: Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology 2006, 104:667-674.
• [12]Suy K, Morias K, Cammu G, Hans P, van Duijnhoven WG, Heeringa M, Demeyer I: Effective reversal of moderate rocuronium- or vecuronium-induced neuromuscular block with sugammadex, a selective relaxant binding agent. Anesthesiology 2007, 106:283-288.
• [13]de Kam PJ, van Kuijk J, Prohn M, Thomsen T, Peeters P: Effects of sugammadex doses up to 32 mg/kg alone or in combination with rocuronium or vecuronium on QTc prolongation: a thorough QTc study. Clin Drug Investig 2010, 30:599-611.
• [14]Peeters PA, van den Heuvel MW, van Heumen E, Passier PC, Smeets JM, van Iersel T, Zwiers A: Safety, tolerability and pharmacokinetics of sugammadex using single high doses (up to 96 mg/kg) in healthy adult subjects: a randomized, double-blind, crossover, placebo-controlled, single-centre study. Clin Drug Investig 2010, 30:867-874.
• [15]Menéndez-Ozcoidi L, Ortiz-Gómez JR, Olaguibel-Ribero JM, Salvador-Bravo MH: Allergy to low dose sugammadex. Anaesthesia 2011, 66:217-219.
• [16]Godai K, Hasegawa-Moriyama M, Kuniyoshi T, Kakoi T, Ikoma K, Isowaki S, Matsunaga A, Kanmura Y: Three cases of suspected sugammadex-induced hypersensitivity reactions. Br J Anaesth 2012, 109:216-218.
• [17]Soria A, Motamed C, Gaouar H, Chemam S, Amsler E, Francès C: Severe reaction following sugammadex injection: hypersensitivity? J Investig Allergol Clin Immunol 2012, 22:382.
• [18]Bridion SmPC 2012 http://www.medicines.org.uk/emc/medicine/21299 webcite
• [19]Yousefshahi F, Anbarafshan M, Khashayar P: Dermal reaction and bigeminal premature ventricular contractions due to neostigmine: a case report. J Med Case Rep 2011, 25(5):83.
• [20]Seed MJ, Ewan PW: Anaphylaxis caused by neostigmine. Anaesthesia 2000, 55:574-575.
• [21]de Kam PJ, El Galta R, Kruithof AC, Fennema H, van Lierop MJ, Mihara K, Burggraaf J, Moerland M, Peeters P, Troyer MD: No clinically relevant interaction between sugammadex and aspirin on platelet aggregation and coagulation parameters. Int J Clin Pharmacol Ther 2013, 51:976-985.
• [22]de Kam PJ, Grobara P, Prohn M, Höppener F, Kluft C, Burggraaf J, Langdon RB, Peeters P: Effects of sugammadex on activated partial thromboplastin time and prothrombin time in healthy subjects. Int J Clin Pharmacol Ther 2014, 2014:2014. Epub ahead of print
• [23]Rahe-Meyer N, Schulman S, Klimscha W, Przemeck M, Blobner M, Wulf HF Fennema H: Sugammadex reversal of rocuronium- or vecuronium-induced neuromuscular blockade is not associated with an increased risk of either bleeding or blood loss compared with usual care. Anesth Analg 2013, 116(Suppl 1):S-48.
• [24]Lee E, Ryan S, Birmingham B, Zalikowski J, March R, Ambrose H, Moore R, Lee C, Chen Y, Schneck D: Rosuvastatin pharmacokinetics and pharmaocogenetics in white and Asian subjects reading in the same environment. Clin Pharmacol Ther 2005, 78:330-341.
• [25]Liao JK: Safety and efficacy of statins in Asians. Am J Cardiol 2007, 99:410-414.
• [26]Zhou HH, Adeoyin A, Wood AJ: Differing effect of atropine on heart rate in Chinese and white subjects. Clin Pharmacol Ther 1992, 52:120-124.
• [27]McGraw J, Waller D: Cytochrome P450 variations in different ethnic populations. Expert Opin Drug Metab Toxicol 2012, 8:371-382.
• [28]Daily EB, Aquilante CL: Cytochrome P450 2C8 pharmacogenetics: a review of clinical studies. Pharmacogenomics 2009, 10:1489-1510.
• [29]Kumana CR, Lauder IJ, Chan M, Ko W, Lin HJ: Differences in diazepam pharmacokinetics in Chinese and white Caucasians–relation to body lipid stores. Eur J Clin Pharmacol 1987, 32:211-215.
• [30]Collins LM, Bevan JC, Bevan DR, Villar GC, Kahwaji R, Smith MF, Donati F: The prolonged duration of rocuronium in Chinese patients. Anesth Analg 2000, 91:1526-1530.
• [31]Fisher DM: Clinical pharmacology of neuromuscular blocking agents. Am J Health Sys Pharm 1999, 56(Suppl 1):S4-S9.
• [32]Yu B, Wang X, Huang W, Li S, Ding Z, Abels A, Rietbergen H, Woo T, Pendeville P: Sugammadex 4.0 mg kg–1 reversal of deep rocuronium-induced neuromuscular blockade: a multicenter study in chinese and caucasian patients. J Anesth Clin Res 2014, 5:408.