Skip to main content
SpringerLink
Log in

Sugammadex: A Review of Neuromuscular Blockade Reversal

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Sugammadex (Bridion®) is a modified γ-cyclodextrin that reverses the effect of the steroidal nondepolarizing neuromuscular blocking agents rocuronium and vecuronium. Intravenous sugammadex resulted in rapid, predictable recovery from moderate and deep neuromuscular blockade in patients undergoing surgery who received rocuronium or vecuronium. Recovery from moderate neuromuscular blockade was significantly faster with sugammadex 2 mg/kg than with neostigmine, and recovery from deep neuromuscular blockade was significantly faster with sugammadex 4 mg/kg than with neostigmine or spontaneous recovery. In addition, recovery from neuromuscular blockade was significantly faster when sugammadex 16 mg/kg was administered 3 min after rocuronium than when patients spontaneously recovered from succinylcholine. Sugammadex also demonstrated efficacy in various special patient populations, including patients with pulmonary disease, cardiac disease, hepatic dysfunction or myasthenia gravis and morbidly obese patients. Intravenous sugammadex was generally well tolerated. In conclusion, sugammadex is an important option for the rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bom A, Bradley M, Cameron K, et al. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrin-based synthetic host. Angew Chem Int Ed Engl. 2002;41(2):266–70.

    Article  PubMed  Google Scholar 

  2. Miller RD. Sugammadex: an opportunity to change the practice of anesthesiology? Anesth Analg. 2007;104(3):477–8.

    Article  PubMed  Google Scholar 

  3. Bartkowski RR. Incomplete reversal of pancuronium neuromuscular blockade by neostigmine, pyridostigmine, and edrophonium. Anesth Analg. 1987;66(7):594–8.

    Article  CAS  PubMed  Google Scholar 

  4. Donati F. Sugammadex: an opportunity for more thinking or more cookbook medicine? Can J Anaesth. 2007;54(9):689–95.

    Article  PubMed  Google Scholar 

  5. European Medicines Agency. Bridion (sugammadex): EPAR summary for the public. 2008. http://www.ema.europa.eu/. Accessed 8 Jun 2016.

  6. Merck & Co. Bridion® (sugammadex) injection, for intravenous use: US prescribing information. 2015. http://www.accessdata.fda.gov/. Accessed 8 Jun 2016.

  7. Naguib M. Sugammadex: another milestone in clinical neuromuscular pharmacology. Anesth Analg. 2007;104(3):575–81.

    Article  CAS  PubMed  Google Scholar 

  8. Gijsenbergh F, Ramael S, Houwing N, et al. First human exposure of Org 25969, a novel agent to reverse the action of rocuronium bromide. Anesthesiology. 2005;103(4):695–703.

    Article  CAS  PubMed  Google Scholar 

  9. White PF, Tufanogullari B, Sacan O, et al. The effect of residual neuromuscular blockade on the speed of reversal with sugammadex. Anesth Analg. 2009;108(3):846–51.

    Article  CAS  PubMed  Google Scholar 

  10. Vanacker BF, Vermeyen KM, Struys MMRF, et al. Reversal of rocuronium-induced neuromuscular block with the novel drug sugammadex is equally effective under maintenance anesthesia with propofol or sevoflurane. Anesth Analg. 2007;104(3):563–8.

    Article  CAS  PubMed  Google Scholar 

  11. Rex C, Wagner S, Spies C, et al. Reversal of neuromuscular blockade by sugammadex after continuous infusion of rocuronium in patients randomized to sevoflurane or propofol maintenance anesthesia. Anesthesiology. 2009;111(1):30–5.

    Article  CAS  PubMed  Google Scholar 

  12. Illman H, Antila H, Olkkola KT. Reversal of neuromuscular blockade by sugammadex does not affect EEG derived indices of depth of anesthesia. J Clin Monit Comput. 2010;24(5):371–6.

    Article  PubMed  Google Scholar 

  13. Fassoulaki A, Chondrogiannis K, Staikou C. Sugammadex at both high and low doses does not affect the depth of anesthesia or hemodynamics: a randomized double blind trial. J Clin Monit Comput. 2016. doi:10.1007/s10877-016-9844-6.

    PubMed  Google Scholar 

  14. Dahaba AA, Bornemann H, Hopfgartner E, et al. Effect of sugammadex or neostigmine neuromuscular block reversal on bispectral index monitoring of propofol/remifentanil anaesthesia. Br J Anaesth. 2012;108(4):602–6.

    Article  CAS  PubMed  Google Scholar 

  15. de Kam P-J, Grobara P, Prohn M, et al. Effects of sugammadex on activated partial thromboplastin time and prothrombin time in healthy subjects. Int J Clin Pharmacol Ther. 2014;52(3):227–36.

    Article  PubMed  Google Scholar 

  16. Rahe-Meyer N, Fennema H, Schulman S, et al. Effect of reversal of neuromuscular blockade with sugammadex versus usual care on bleeding risk in a randomized study of surgical patients. Anesthesiology. 2014;121(5):969–77.

    Article  PubMed  Google Scholar 

  17. de Kam P-J, El Galta R, Kruithof AC, et al. No clinically relevant interaction between sugammadex and aspirin on platelet aggregation and coagulation parameters. Int J Clin Pharmacol Ther. 2013;51(12):976–85.

    Article  PubMed  Google Scholar 

  18. de Kam P-J, Kruithof AC, van Lierop M-J, et al. Lack of a clinically relevant effect of sugammadex on anti-Xa activity or activated partial thromboplastin time following pretreatment with either unfractionated or low-molecular-weight heparin in healthy subjects. Int J Clin Pharmacol Ther. 2014;52(8):631–41.

    Article  PubMed  Google Scholar 

  19. Raft J, Guerci P, Harter V, et al. Biological evaluation of the effect of sugammadex on hemostasis and bleeding. Korean J Anesthesiol. 2015;68(1):17–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Cammu G, Coart D, De Graeve K, et al. Reversal of rocuronium-induced neuromuscular block with sugammadex in heart failure patients: a prospective observational study. Acta Anaesthesiol Belg. 2012;63(2):69–73.

    CAS  PubMed  Google Scholar 

  21. de Kam P-J, van Kuijk J, Prohn M, et al. 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(9):599–611.

    Article  PubMed  Google Scholar 

  22. de Kam P-J, van Kuijk J, Smeets J, et al. Sugammadex is not associated with QT/QTc prolongation: methodology aspects of an intravenous moxifloxacin-controlled thorough QT study. Int J Clin Pharmacol Ther. 2012;50(8):595–604.

    Article  PubMed  Google Scholar 

  23. de Kam P-J, Grobara P, Dennie J, et al. Effect of sugammadex on QT/QTc interval prolongation when combined with QTc-prolonging sevoflurane or propofol anaesthesia. Clin Drug Investig. 2013;33(8):545–51.

    Article  PubMed  Google Scholar 

  24. Zwiers A, van den Heuvel M, Smeets J, et al. Assessment of the potential for displacement interactions with sugammadex: a pharmacokinetic-pharmacodynamic modelling approach. Clin Drug Investig. 2011;31(2):101–11.

    Article  CAS  PubMed  Google Scholar 

  25. European Medicines Agency. Bridion (sugammadex) 100 mg/mL solution for injection: EU summary of product characteristics. 2015. http://www.ema.europa.eu/. Accessed 8 Jun 2016.

  26. de Kam P-J, van den Heuvel MW, Grobara P, et al. Flucloxacillin and diclofenac do not cause recurrence of neuromuscular blockade after reversal with sugammadex. Clin Drug Investig. 2012;32(3):203–12.

    Article  PubMed  Google Scholar 

  27. Pühringer FK, Gordon M, Demeyer I, et al. Sugammadex rapidly reverses moderate rocuronium- or vecuronium-induced neuromuscular block during sevoflurane anaesthesia: a dose-response relationship. Br J Anaesth. 2010;105(5):610–9.

    Article  PubMed  Google Scholar 

  28. Peeters P, Passier P, Smeets J, et al. Sugammadex is cleared rapidly and primarily unchanged via renal excretion. Biopharm Drug Dispos. 2011;32(3):159–67.

    Article  CAS  PubMed  Google Scholar 

  29. Staals LM, Snoeck MMJ, Driessen JJ, et al. Reduced clearance of rocuronium and sugammadex in patients with severe to end-stage renal failure: a pharmacokinetic study. Br J Anaesth. 2010;104(1):31–9.

    Article  CAS  PubMed  Google Scholar 

  30. McDonagh DL, Benedict PE, Kovac AL, et al. Efficacy, safety, and pharmacokinetics of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in elderly patients. Anesthesiology. 2011;114(2):318–29.

    Article  CAS  PubMed  Google Scholar 

  31. de Kam P-J, Hou J, Wang Z, et al. Pharmacokinetics of sugammadex 16 mg/kg in healthy Chinese volunteers. Int J Clin Pharmacol Ther. 2015;53(6):456–61.

    Article  PubMed  Google Scholar 

  32. Plaud B, Meretoja O, Hofmockel R, et al. Reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients. Anesthesiology. 2009;110(2):284–94.

    CAS  PubMed  Google Scholar 

  33. Sorgenfrei IF, Norrild K, Larsen PB, et al. Reversal of rocuronium-induced neuromuscular block by the selective relaxant binding agent sugammadex: a dose-finding and safety study. Anesthesiology. 2006;104(4):667–74.

    Article  CAS  PubMed  Google Scholar 

  34. Suy K, Morias K, Cammu G, et al. Effective reversal of moderate rocuronium- or vecuronium-induced neuromuscular block with sugammadex, a selective relaxant binding agent. Anesthesiology. 2007;106(2):283–8.

    Article  CAS  PubMed  Google Scholar 

  35. Takeda J, Iwasaki H, Yamakage M, et al. Efficacy and safety of sugammadex (Org 25969) in reversing moderate neuromuscular block induced by rocuronium or vecuronium in Japanese patients [in Japanese]. Masui. 2014;63(10):1075–82.

    PubMed  Google Scholar 

  36. Tassonyi E, Pongrácz A, Nemes R, et al. Reversal of pipecuronium-induced moderate neuromuscular block with sugammadex in the presence of a sevoflurane anesthetic: a randomized trial. Anesth Analg. 2015;121(2):373–80.

    Article  CAS  PubMed  Google Scholar 

  37. Duvaldestin P, Kuizenga K, Saldien V, et al. A randomized, dose-response study of sugammadex given for the reversal of deep rocuronium- or vecuronium-induced neuromuscular blockade under sevoflurane anesthesia. Anesth Analg. 2010;110(1):74–82.

    Article  CAS  PubMed  Google Scholar 

  38. Groudine SB, Soto R, Lien C, et al. A randomized, dose-finding, phase II study of the selective relaxant binding drug, sugammadex, capable of safely reversing profound rocuronium-induced neuromuscular block. Anesth Analg. 2007;104(3):555–62.

    Article  CAS  PubMed  Google Scholar 

  39. Takeda J, Iwasaki H, Otagiri T, et al. Efficacy and safety of sugammadex (Org 25969) in reversing deep neuromuscular block induced by rocuronium or vecuronium in Japanese patients [in Japanese]. Masui. 2014;63(10):1083–8.

    PubMed  Google Scholar 

  40. Sparr HJ, Vermeyen KM, Beaufort AM, et al. Early reversal of profound rocuronium-induced neuromuscular blockade by sugammadex in a randomized multicenter study: efficacy, safety, and pharmacokinetics. Anesthesiology. 2007;106(5):935–43.

    Article  CAS  PubMed  Google Scholar 

  41. Pühringer FK, Rex C, Sielenkamper AW, et al. Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial. Anesthesiology. 2008;109(2):188–97.

    Article  PubMed  Google Scholar 

  42. de Boer HD, Driessen JJ, Marcus MAE, et al. Reversal of rocuronium-induced (1.2 mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study. Anesthesiology. 2007;107(2):239–44.

    Article  PubMed  Google Scholar 

  43. Blobner M, Eriksson LI, Scholz J, et al. 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(10):874–81.

    Article  CAS  PubMed  Google Scholar 

  44. Flockton EA, Mastronardi P, Hunter JM, et al. Reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine. Br J Anaesth. 2008;100(5):622–30.

    Article  CAS  PubMed  Google Scholar 

  45. Woo T, Kim KS, Shim YH, et al. Sugammadex versus neostigmine reversal of moderate rocuronium-induced neuromuscular blockade in Korean patients. Korean J Anesthesiol. 2014;65(6):501–7.

    Article  Google Scholar 

  46. Wu X, Oerding H, Liu J, et al. Rocuronium blockade reversal with sugammadex vs. neostigmine: randomized study in Chinese and Caucasian subjects. BMC anesthesiology. 2014;14:53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Khuenl-Brady KS, Wattwil M, Vanacker BF, et al. Sugammadex provides faster reversal of vecuronium-induced neuromuscular blockade compared with neostigmine: a multicenter, randomized, controlled trial. Anesth Analg. 2010;110(1):64–73.

    Article  PubMed  Google Scholar 

  48. Illman HL, Laurila P, Antila H, et al. The duration of residual neuromuscular block after administration of neostigmine or sugammadex at two visible twitches during train-of-four monitoring. Anesth Analg. 2011;112(1):63–8.

    Article  CAS  PubMed  Google Scholar 

  49. Geldner G, Niskanen M, Laurila P, et al. A randomised controlled trial comparing sugammadex and neostigmine at different depths of neuromuscular blockade in patients undergoing laparoscopic surgery. Anaesthesia. 2012;67(9):991–8.

    Article  CAS  PubMed  Google Scholar 

  50. Jones RK, Caldwell JE, Brull SJ, et al. Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine. Anesthesiology. 2008;109(5):816–24.

    Article  CAS  PubMed  Google Scholar 

  51. Lemmens HJM, M.I. E-O, Berry J, et al. Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine. BMC Anesthesiol. 2010;10: 15.

  52. Rahe-Meyer N, Berger C, Wittmann M, et al. Recovery from prolonged deep rocuronium-induced neuromuscular blockade: a randomized comparison of sugammadex reversal with spontaneous recovery. Anaesthesist. 2015;64(7):506–12.

    Article  CAS  PubMed  Google Scholar 

  53. Soto R, Jahr JS, Pavlin J, et al. Safety and efficacy of rocuronium with sugammadex reversal versus succinylcholine in outpatient surgery: a multicenter, randomized, safety assessor-blinded trial. Am J Ther. 2015. doi:10.1097/MJT.0000000000000206.

    PubMed  Google Scholar 

  54. Sabo D, Jahr J, Pavlin J, et al. The increases in potassium concentrations are greater with succinylcholine than with rocuronium-sugammadex in outpatient surgery: a randomized, multicentre trial. Can J Anaesth. 2014;61(5):423–32.

    Article  PubMed  Google Scholar 

  55. Lee C, Jahr JS, Candiotti KA, et al. Reversal of profound neuromuscular block by sugammadex administered three minutes after rocuronium: a comparison with spontaneous recovery from succinylcholine. Anesthesiology. 2009;110(5):1020–5.

    Article  CAS  PubMed  Google Scholar 

  56. Amao R, Zornow MH, Cowan RM, et al. Use of sugammadex in patients with a history of pulmonary disease. J Clin Anesth. 2012;24(4):289–97.

    Article  PubMed  Google Scholar 

  57. Dahl V, Pendeville PE, Hollmann MW, et al. Safety and efficacy of sugammadex for the reversal of rocuronium-induced neuromuscular blockade in cardiac patients undergoing noncardiac surgery. Eur J Anaesthesiol. 2009;26(10):874–84.

    Article  CAS  PubMed  Google Scholar 

  58. Fujita A, Ishibe N, Yoshihara T, et al. Rapid reversal of neuromuscular blockade by sugammadex after continuous infusion of rocuronium in patients with liver dysfunction undergoing hepatic surgery. Acta Anaesthesiol Taiwan. 2014;52(2):54–8.

    Article  PubMed  Google Scholar 

  59. Carron M, Veronese S, Foletto M, et al. Sugammadex allows fast-track bariatric surgery. Obes Surg. 2013;23(10):1558–63.

    Article  PubMed  Google Scholar 

  60. Vymazal T, Krecmerova M, Bicek V, et al. Feasibility of full and rapid neuromuscular blockade recovery with sugammadex in myasthenia gravis patients undergoing surgery: a series of 117 cases. Ther Clin Risk Manag. 2015;11:1593–6.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Min KC, Bondiskey P, Schulz V, et al. Evaluation of hypersensitivity incidence following repeated single-dose sugammadex administration in healthy subjects [abstract no. 1AP15-9]. Eur J Anaesthesiol. 2015;32(Suppl 53):57.

    Google Scholar 

  62. Food and Drug Administration. Sugammadex medical review: application number 022225Orig1s000. 2015. http://www.accessdata.fda.gov/. Accessed 8 Jun 2016.

  63. Naguib M, Kopman AF, Lien CA, et al. A survey of current management of neuromuscular block in the United States and Europe. Anesth Analg. 2010;111(1):110–9.

    PubMed  Google Scholar 

  64. Apfelbaum JL, Silverstein JH, Chung FF, et al. Practice guidelines for postanesthetic care: an updated report by the American Society of Anesthesiologists Task Force on Postanesthetic Care. Anesthesiology. 2013;118(2):291–307.

    Article  PubMed  Google Scholar 

  65. Kotake Y, Ochiai R, Suzuki T, et al. Reversal with sugammadex in the absence of monitoring did not preclude residual neuromuscular block. Anesth Analg. 2013;117(2):345–51.

    Article  PubMed  Google Scholar 

  66. Sorensen MK, Bretlau C, Gatke MR, et al. Rapid sequence induction and intubation with rocuronium-sugammadex compared with succinylcholine: a randomized trial. Br J Anaesth. 2012;108(4):682–9.

    Article  CAS  PubMed  Google Scholar 

  67. Williamson RM, Mallaiah S, Barclay P. Rocuronium and sugammadex for rapid sequence induction of obstetric general anaesthesia. Acta Anaesthesiol Scand. 2011;55(6):694–9.

    Article  CAS  PubMed  Google Scholar 

  68. Stourac P, Adamus M, Seidlova D, et al. Low-dose or high-dose rocuronium reversed with neostigmine or sugammadex for cesarean delivery anesthesia: a randomized controlled noninferiority trial of time to tracheal intubation and extubation. Anesth Analg. 2016;122(5):1536–45.

    Article  CAS  PubMed  Google Scholar 

  69. Lenz A, Hill G, White PF. Emergency use of sugammadex after failure of standard reversal drugs. Anesth Analg. 2007;104(3):585–6.

    Article  CAS  PubMed  Google Scholar 

  70. de Menezes CC, Peceguini LA, Silva ED, et al. Use of sugammadex after neostigmine incomplete reversal of rocuronium-induced neuromuscular blockade. Rev Bras Anestesiol. 2012;62(4):543–7.

    Article  PubMed  Google Scholar 

  71. Pongracz A, Szatmari S, Nemes R, et al. Reversal of neuromuscular blockade with sugammadex at the reappearance of four twitches to train-of-four stimulation. Anesthesiology. 2013;119(1):36–42.

    Article  CAS  PubMed  Google Scholar 

  72. Kaufhold N, Schaller SJ, Stauble CG, et al. Sugammadex and neostigmine dose-finding study for reversal of residual neuromuscular block at a train-of-four ratio of 0.2 (SUNDRO20). Br J Anaesth. 2016;116:233–40.

    Article  CAS  PubMed  Google Scholar 

  73. Schaller SJ, Fink H, Ulm K, et al. Sugammadex and neostigmine dose-finding study for reversal of shallow residual neuromuscular block. Anesthesiology. 2010;113(5):1054–60.

    Article  PubMed  Google Scholar 

  74. Cammu G, van Vlem B, van den Heuvel M, et al. Dialysability of sugammadex and its complex with rocuronium in intensive care patients with severe renal impairment. Br J Anaesth. 2012;109(3):382–90.

    Article  CAS  PubMed  Google Scholar 

  75. Staals LM, Snoeck MM, Driessen JJ, et al. Multicentre, parallel-group, comparative trial evaluating the efficacy and safety of sugammadex in patients with end-stage renal failure or normal renal function. Br J Anaesth. 2008;101(4):492–7.

    Article  CAS  PubMed  Google Scholar 

  76. Iwasaki H, Sasakawa T, Takahoko K, et al. A case series of re-establishment of neuromuscular block with rocuronium after sugammadex reversal. J Anesth. 2016;30(3):534–7.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

During the peer review process, the manufacturer of sugammadex was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

Author information

Authors and Affiliations

  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Gillian M. Keating

Authors
  1. Gillian M. Keating
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gillian M. Keating.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

Gillian Keating is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: S.J. Brull, Department of Anesthesiology, Mayo Clinic, Jacksonville, FL, USA; G. Della-Rocca, Department of Anesthesia and Intensive Care Medicine, University of Udine, Udine, Italy; G.F. Geldner, Klinik für Anästhesiologie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Klinikum Ludwigsburg, Ludwigsburg, Germany; T. Heier, Department of Anesthesia, Division of Emergencies and Critical Care Medicine, Oslo University Hospital and University of Oslo, Oslo, Norway; H.J.M. Lemmens, Department of Anesthesia, Stanford University School of Medicine, Stanford, CA, USA; J.R. Renew, Department of Anesthesiology, Mayo Clinic, Jacksonville, FL, USA; F.S. Servin, Département d’Anesthésie-Réanimation, APHP-Hôpital Bichat-Claude Bernard, Paris, France.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Keating, G.M. Sugammadex: A Review of Neuromuscular Blockade Reversal. Drugs 76, 1041–1052 (2016). https://doi.org/10.1007/s40265-016-0604-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-016-0604-1

Keywords

Search

Navigation