Drugs

, Volume 69, Issue 7, pp 919–942 | Cite as

Sugammadex

A Review of its Use in Anaesthetic Practice
Adis Drug Evaluation

Summary

Abstract

Sugammadex (Bridion®), a modified γ-cyclodextrin, is the first selective relaxant binding agent indicated to reverse the neuromuscular blockade induced during general anaesthesia to facilitate surgical procedures. The mechanism of action of sugammadex differs from that of other commonly used reversal agents, such as neostigmine and edrophonium. In the EU, sugammadex is recommended for use in the reversal of rocuronium- or vecuronium-induced moderate or deep muscle relaxation in adult (including elderly) patients and reversal of rocuronium-induced moderate muscle relaxation in paediatric patients (aged 2–17 years). Sugammadex is also approved in Australia, Iceland, New Zealand and Norway.

In clinical trials in adult surgical patients with relatively good health, sugammadex at recommended doses provided rapid reversal of rocuronium- or vecuronium-induced neuromuscular blockade with a low incidence of residual or recurrent neuromuscular blockade and was generally well tolerated. In paediatric patients, sugammadex effectively reversed rocuronium-induced neuromuscular blockade and was generally well tolerated. Several factors associated with the use of sugammadex have yet to be determined, such as the efficacy and safety in patients with poorer health or in those with neuromuscular disorders, the incidence of infrequent adverse events in larger patient populations and the cost effectiveness of the drug relative to existing reversal agents. Nevertheless, sugammadex is a useful addition to the reversal agents commonly employed in anaesthetic practice.

Pharmacological Properties

Sugammadex encapsulates and inactivates rocuronium; it selectively binds to free rocuronium molecules with high affinity at a molar ratio of 1:1. The resulting inactive complex is eliminated from the body according to the pharmacokinetic properties of sugammadex. Sugammadex also has high affinity for vecuronium. In several phase I and II trials, sugammadex demonstrated dose-dependent reversal of rocuronium- or vecuronium-induced blockade when administered at the reappearance of the second twitch of the train-of-four stimulation (T2) or at a post-tetanic count of 1–2 (1–2 PTC), or 3–15 minutes after the administration of the neuromuscular blocking agent. Sugammadex has no clinically relevant effects on the cardiovascular and haemodynamic systems (including corrected QT interval prolongation).

Intravenous sugammadex demonstrates linear pharmacokinetic properties over the dose range of 1–16 mg/kg. The steady-state volume of distribution after a single dose is ≈1-14 L. Sugammadex and the sugammadex-rocuronium complex do not bind to plasma proteins or erythrocytes. Sugammadex does not appear to undergo metabolism and is primarily excreted in the urine as unchanged drug; the elimination half-life is 1.8 hours. Administration of sugammadex following that of rocuronium increases the plasma concentration of rocuronium (in a manner dependent on the dose of sugammadex), shortens its elimination half-life (by ≈30%) and increases the urinary excretion (by 2- to 3-fold) of rocuronium; however, these changes are not associated with an increase in the level of neuro-muscular blockade. Unlike rocuronium, the sugammadex-rocuronium complex is not eliminated via the biliary route. Renal impairment (but not hepatic impairment or patient age) delays the elimination of sugammadex and the sugammadex-rocuronium complex, and the use of sugammadex in patients with severe renal impairment is not recommended.

Therapeutic Efficacy

The efficacy of sugammadex has been evaluated in several well designed phase III trials in adult (including elderly) or paediatric surgical patients. In adult patients, sugammadex 2 mg/kg reversed rocuronium 0.6 mg/kg or vecuronium O.l mg/kg significantly faster than neostigmine 50 μg/kg plus glycopyrrolate 10 μg/kg, when administered at the reappearance of T2. In addition, the reversal of rocuronium 0.6 mg/kg by sugammadex 2 mg/kg was significantly faster than the reversal of cisatracurium 0.15 mg/kg by neostigmine 50μg/kg plus glycopyrrolate 10μg/kg. Sugammadex 4 mg/kg reversed rocuronium 0.6 mg/kg or vecuronium 0.1 mg/kg significantly faster than neostigmine 70 μg/kg plus glycopyrrolate 14 μg/kg, when administered at 1–2 PTC. When administered 3 minutes after rocuronium, sugammadex 16 mg/kg reversed rocuronium 1.2 mg/kg significantly faster than the spontaneous recovery after suxamethonium chloride (succinylcholine).

The time to reverse neuromuscular blockade with sugammadex 2 mg/kg administered at the reappearance of T2 following rocuronium 0.6 mg/kg was slower in elderly than in younger adult patients; however, reversal was reached in <4 minutes in the majority (75.5%) of elderly patients. In infants, children, adolescents and adults receiving sugammadex 2 mg/kg following rocuronium 0.6 mg/kg, the mean time to neuromuscular blockade reversal was <1.9 minutes. The efficacy of sugammadex 2 mg/kg did not differ between patients with normal renal function and those with severe renal impairment. Underlying cardiac or pulmonary disease had no effect on the efficacy of sugammadex.

Tolerability

Sugammadex was generally well tolerated in clinical trials in surgical patients (including elderly or paediatric patients, or patients with renal impairment or cardiac or pulmonary disease) or healthy volunteers. The majority of adverse events considered to be related to sugammadex were mild to moderate in severity. The most commonly reported adverse events in any study group were procedural pain, nausea and vomiting. In pooled analyses, the tolerability profile of sugammadex was generally similar to that of placebo or neostigmine plus glycopyrrolate; serious adverse events were infrequent. Uncommon adverse events include anaesthetic complications and dysgeusia in awake healthy volunteers, which were more frequent with higher than recommended doses of sugammadex (≥16 mg/kg), and residual or recurrent neuromuscular blockade which was more frequent with lower than recommended doses of sugammadex (<2mg/kg).

References

  1. 1.
    Bowman WC. Neuromuscular block. Br J Pharmacol 2006 Jan; 147 Suppl. 1: S277–86PubMedCrossRefGoogle Scholar
  2. 2.
    Utting JE. The era of relaxant anaesthesia. Br J Anaesth 1992 Dec; 69(6): 551–3PubMedCrossRefGoogle Scholar
  3. 3.
    de Boer HD, van Egmond J, Driessen JJ, et al. Update on the management of neuromuscular block: focus on su-gammadex. Neuropsych Dis Treat 2007; 3(5): 539–44Google Scholar
  4. 4.
    Nicholson WT, Sprung J, Jankowski CJ. Sugammadex: a novel agent for the reversal of neuromuscular blockade. Pharmacotherapy 2007 Aug; 27(8): 1181–8PubMedCrossRefGoogle Scholar
  5. 5.
    Wiklund RA, Rosenbaum SH. Anesthesiology: first of two parts. N Engl J Med 1997 Oct 16; 337(16): 1132–41PubMedCrossRefGoogle Scholar
  6. 6.
    Baraka A. Suxamethonium-neostigmine interaction in patients with normal of atypical cholinesterase. Br J Anaesth 1977 May; 49(5): 479–84PubMedCrossRefGoogle Scholar
  7. 7.
    Miller RD. Sugammadex: an opportunity to change the practice of anesthesiology? Anesth Analg 2007 Mar; 104(3): 477–8PubMedCrossRefGoogle Scholar
  8. 8.
    Magorian T, Flannery KB, Miller RD. Comparison of rocuronium, succinylcholine, and vecuronium for rapid-sequence induction of anesthesia in adult patients. Anesthesiology 1993 Nov; 79(5): 913–8PubMedCrossRefGoogle Scholar
  9. 9.
    Raghavendra T. Neuromuscular blocking drugs: discovery and development. J R Soc Med 2002 Jul; 95(7): 363–7PubMedCrossRefGoogle Scholar
  10. 10.
    Karcioglu O, Arnold J, Topacoglu H, et al. Succinylcholine or rocuronium? A meta-analysis of the effects on intubation conditions. Int J Clin Pract 2006 Dec; 60(12): 1638–46PubMedCrossRefGoogle Scholar
  11. 11.
    GlaxoSmithKline UK. Anectine injection (suxamethonium chloride): summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk/emc/assets/c/html/displayDocPrinterFriendly.asp?documentid=704 [Accessed 2008 Sep 26]
  12. 12.
    NV Organon. Esmeron® (rocuronium bromide) 10mg/mL solution for injection: summary of product characteristics [online]. Available from URL: http://emc.medicines.org.uk/emc/assets/c/html/displayDocPrinterFriendly.asp?documentid=5166 [Accessed 2008 Oct 9]
  13. 13.
    Caldwell JE. Clinical limitations of acetylcholinesterase antagonists. J Crit Care 2009 Mar; 24(1): 21–8PubMedCrossRefGoogle Scholar
  14. 14.
    Donati F. Sugammadex: an opportunity for more thinking or more cookbook medicine? Can J Anesth 2007 Sep; 54(9): 689–95PubMedCrossRefGoogle Scholar
  15. 15.
    Adam JM, Bennett DJ, Bom A, et al. Cyclodextrin-derived host molecules as reversal agents for the neuromuscular blocker rocuronium bromide: synthesis and structure-activity relationships. J Med Chem 2002 Apr 25; 45(9): 1806–16PubMedCrossRefGoogle Scholar
  16. 16.
    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 Jan 18; 41(2): 266–70PubMedCrossRefGoogle Scholar
  17. 17.
    Loftsson T, Duchêne D. Cyclodextrins and their pharmaceutical applications. Int J Pharm 2007 Feb 1; 329(1–2): 1–11PubMedCrossRefGoogle Scholar
  18. 18.
    Stella VJ, He Q. Cyclodextrins. Toxicol Pathol 2008; 36(1): 30–42PubMedCrossRefGoogle Scholar
  19. 19.
    Challa R, Ahuja A, Ali J, et al. Cyclodextrins in drug delivery: an updated review. AAPS PharmSciTech 2005 Oct 14; 6(2): E329–57PubMedCrossRefGoogle Scholar
  20. 20.
    Schering-Plough Corp. Bridion® (sugammadex sodium) injection: first and only selective relaxant binding agent approved in European Union [online]. Available from URL: http://www.schering-plough.com/schering_plough/news/release.jsp?releaseID=1180933 [Accessed 2008 Aug 20]
  21. 21.
    Zhang M-Q. Drug-specific cyclodextrins: the future of rapid neuromuscular block reversal? Drugs Future 2003 Apr; 28(4): 347–54CrossRefGoogle Scholar
  22. 22.
    Epemolu O, Bom A, Hope F, et al. Reversal of neuromuscular blockade and simultaneous increase in plasma rocuronium concentration after the intravenous infusion of the novel reversal agent Org 25969. Anesthesiology 2003 Sep; 99(3): 632–7PubMedCrossRefGoogle Scholar
  23. 23.
    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 May; 106(5): 935–43PubMedCrossRefGoogle Scholar
  24. 24.
    Epemolu O, Mayer I, Hope F, et al. Liquid chrom-atography/mass spectrometric bioanalysis of a modified γ-cyclodextrin (Org 25969) and rocuronium bromide (Org 9426) in guinea pig plasma and urine: its application to determine the plasma pharmacokinetics of Org 25969. Rapid Commun Mass Spectrom 2002; 16(20): 1946–52PubMedCrossRefGoogle Scholar
  25. 25.
    de Boer HD, van Egmond J, van de Pol F, et al. Sugammadex, a new reversal agent for neuromuscular block induced by rocuronium in the anaesthetized Rhesus monkey. Br J Anaesth 2006 Apr; 96(4): 473–9PubMedCrossRefGoogle Scholar
  26. 26.
    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 Mar; 104(3): 555–62PubMedCrossRefGoogle Scholar
  27. 27.
    Shields M, Giovannelli M, Mirakhur RK, et al. Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block. Br J Anaesth 2006 Jan; 96(1): 36–43PubMedCrossRefGoogle Scholar
  28. 28.
    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 Apr; 104(4): 667–74PubMedCrossRefGoogle Scholar
  29. 29.
    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 Feb; 106(2): 283–8PubMedCrossRefGoogle Scholar
  30. 30.
    Pühringer FK, Rex C, Sielenkämper 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 Aug; 109(2): 188–97PubMedCrossRefGoogle Scholar
  31. 31.
    de Boer HD, Driessen JJ, Marcus MAE, et al. Reversal of rocuronium-induced (1.2mg/kg) profound neuromuscular block by sugammadex: a multicenter, dose-finding and safety study. Anesthesiology 2007 Aug; 107(2): 239–44PubMedCrossRefGoogle Scholar
  32. 32.
    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 Oct; 103(4): 695–703PubMedCrossRefGoogle Scholar
  33. 33.
    Vanacker BF, Vermeyen KM, Struys MMR, 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 Mar; 104(3): 563–8PubMedCrossRefGoogle Scholar
  34. 34.
    Wagner S, Pühringer FK, Spies C, et al. Sugammadex reverses neuromuscular blockade after continuous infusion of rocuronium in patients under sevoflurane or propofol maintenance anesthesia [abstract no. S218]. Anesth Analg 2008 Mar; 106 Suppl. 3: S218Google Scholar
  35. 35.
    European Medicines Agency. Bridion (sugammadex sodium) 100 mg/mL: summary of product characteristics [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/bridion/H-885-PI-en.pdf [Accessed 2009 Feb 5]
  36. 36.
    de Kam P-J, van Kuijk J, Smeets J, et al. Single IV sugammadex doses up to 32 mg/kg are not associated with QT/QTc prolongation [abstract no. A1580]. 2007 Annual Meeting of the American Society of Anesthesiologists; 2007 Oct 13–17; San Francisco (CA)Google Scholar
  37. 37.
    de Kam P, van Kuijk J, Prohn M, et al. Single IV sugammadex doses up to 32 mg/kg alone or in combination with rocuronium or vecuronium are not associated with QTc prolongation [abstract no. 9AP5-9]. Eur J Anaes-thesiol 2008 Jun; 25 Suppl. 44: 9AP5–9. Plus poster presented at the 2008 Annual Meeting of the European Society of Anaesthesiology; 2008 May 31–Jun 3; CopenhagenGoogle Scholar
  38. 38.
    Organon USA. FDA Anesthetic and Life Support Advisory Committee Meeting: briefing document (background package) for sugammadex sodium injection [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/08/briefing/2008-4346bl-02-Organon.pdf [Accessed 2008 Oct 2]
  39. 39.
    Fuchs-Buder T, Schreiber J-U, Meistelman C. Monitoring neuromuscular block: an update. Anaesthesia 2009 Mar; 64 Suppl. 1:82–9PubMedCrossRefGoogle Scholar
  40. 40.
    American Society of Anesthesiologists. ASA physical status classification system [online]. Available from URL: http://www.asahq.org/clinical/physicalstatus.htm [Accessed 2008 Sep 26]
  41. 41.
    International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. The clinical evaluation of QT/QTc interval prolongation and proarrhythmic potential for non-antiarrhythmic drugs: E14 [online]. Available from URL: http://www.ich.org/LOB/media/MEDIA1476.pdf [Accessed 2009 Apr 6]
  42. 42.
    Dahl V, Pendeville PE, Hollman MW, et al. Reversal of rocuronium-induced neuromuscular blockade by sugammadex in cardiac patients [abstract no. A1581 plus poster]. 2007 Annual Meeting of the American Society of Anesthesiologists; 2007 Oct 13–17; San Francisco (CA)Google Scholar
  43. 43.
    Eikermann M, Zaremba S, Malhotra A, et al. Neostigmine but not sugammadex impairs upper airway dilator muscle activity and breathing. Br J Anaesth 2008 Sep; 101(3): 344–9PubMedCrossRefGoogle Scholar
  44. 44.
    Staals L, Snoeck M, Hunter J, et al. Pharmacokinetics of rocuronium and sugammadex in patients with normal and impaired renal function [abstract plus poster]. 14th World Congress of Anaesthesiologists; 2008 Mar 2–7; Cape TownGoogle Scholar
  45. 45.
    Khuenl-Brady KS, Sparr H. Clinical pharmacokinetics of rocuronium bromide. Clin Pharmacokinet 1996 Sep; 31(3): 174–83PubMedCrossRefGoogle Scholar
  46. 46.
    Sparr HJ, Beaufort TM, Fuchs-Buder T. Newer neuromus-cular blocking agents: how do they compare with established agents? Drugs 2001; 61(7): 919–42PubMedCrossRefGoogle Scholar
  47. 47.
    Proost JH, Eriksson LI, Mirakhur RK, et al. Urinary, biliary and faecal excretion of rocuronium in humans. Br J An-aesth 2000 Nov; 85(5): 717–23Google Scholar
  48. 48.
    Staals LM, Snoeck MMJ, 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 Oct; 101(4): 492–7PubMedCrossRefGoogle Scholar
  49. 49.
    Plaud B, Meretoja O, Hofmockel R, et al. Reversal of ro-curonium-induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients. Anesthesiology 2009 Feb; 110(2): 284–94PubMedGoogle Scholar
  50. 50.
    Blobner M, Eriksson L, Scholz J, et al. Sugammadex (2.0 mg/kg) significantly faster reverses shallow rocuronium-induced neuromuscular blockade compared with neostigmine (50mg/kg) [abstract no. 9AP7-10]. Eur J Anaesthesiol 2007 Jun; 24: 125. Plus poster presented at the 2007 Congressof the European Society of Anaesthesiology; 2007 Jun 9–12; MunichCrossRefGoogle Scholar
  51. 51.
    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 May; 100(5): 622–30PubMedCrossRefGoogle Scholar
  52. 52.
    Jones RK, Caldwell JE, Brull SJ, et al. Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine. Anesthesiology 2008 Nov; 109(5): 816–24PubMedCrossRefGoogle Scholar
  53. 53.
    Lee C, Jahr JS, Candiotti KA, et al. Reversal of profound neuromuscular block by sugammadex administered 3 minutes after rocuronium: a comparison with spontaneous recovery from succinylcholine. Anesthesiology 2009 May; 110(5): 1020–5PubMedCrossRefGoogle Scholar
  54. 54.
    Alvarez-Gómez JA, Wattwill M, Vanacker B, et al. Reversal of vecuronium-induced shallow neuromuscular blockade is significantly faster with sugammadex compared with neostigmine [abstract no. 9AP7-8]. Eur J Anaesthesiol 2007 Jun; 24 Suppl. 39: 124–5. Plus poster presented at the 2007 Congress of the European Society of Anaesthesiology; 2007 Jun 9–12; MunichCrossRefGoogle Scholar
  55. 55.
    Lemmens HJM, El-Orbany MI, Berry J, et al. Sugammadex reverses profound vecuronium blockade more rapidly than neostigmine [abstract no. A1578 plus poster]. 2007 Annual Meeting of the American Society of Anesthesiologists; 2007 Oct 13–17; San Francisco (CA)Google Scholar
  56. 56.
    Sacan O, White PF, Tufanogullari B, et al. Sugammadex reversal of rocuronium-induced neuromuscular blockade: a comparison with neostigmine-glycopyrrolate and edro-phonium-atropine. Anesth Analg 2007 Mar; 104(3): 569–74PubMedCrossRefGoogle Scholar
  57. 57.
    Pavlin EG, White PF, Viegas OJ, et al. Sugammadex given at least 15 min after rocuronium is effective in reversing neuromuscular blockade [abstract no. A1579 plus poster]. 2007 Annual Meeting of the American Society of Anesthesiologists; 2007 Oct 13–17; San Francisco (CA)Google Scholar
  58. 58.
    McDonagh DL, Benedict PE, Kovac AL, et al. Efficacy and safety of sugammadex for reversal of rocuronium-induced blockade in elderly patients [abstract no. A1583 plus poster]. 2007 Annual Meeting of the American Society of Anesthesiologists; 007 Oct 13–17; San Francisco (CA)Google Scholar
  59. 59.
    Amao R, Zornow MH, McTaggart Cowan R, et al. Sugammadex safely reverses rocuronium-induced blockade in patients with pulmonary disease [abstract no. A1582 plus poster]. 2007 Annual Meeting of the American Society of Anesthesiologists; 2007 Oct 13–17; San Francisco (CA)Google Scholar
  60. 60.
    Monk TG, Rietbergen H, Woo T. Obesity has no clinically relevant impact upon recovery time following administration of sugammadex [abstract no. A682 plus poster]. 2008 Annual Meeting of the American Society of Anesthesiologists; 2008 Oct 18–22; Orlando (FL)Google Scholar
  61. 61.
    Fuchs-Buder T, Claudius C, Skovgaard LT, et al. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision. Acta Anaesthesiol Scand 2007 Aug; 51(7): 789–808PubMedCrossRefGoogle Scholar
  62. 62.
    Cammu G, De Kam PJ, Demeyer I, et al. Safety and toler-ability of single intravenous doses of sugammadex administered simultaneously with rocuronium or vecuronium in healthy volunteers. Br J Anaesth 2008 Mar; 100(3): 373–9PubMedCrossRefGoogle Scholar
  63. 63.
    Peeters P, Passier P, Smeets J, et al. Single intravenous high-dose sugammadex (up to 96 mg/kg) is generally safe and well tolerated in healthy volunteers [abstract no. 9AP3-6]. Eur J Anaesthesiol 2008; 25 Suppl. 4: 9AP3–6. Plus poster presented at the 2008 Congress of the European Society of Anaesthesiology; 2008 May 31–Jun 3; CopenhagenGoogle Scholar
  64. 64.
    Molina AL, de Boer HD, Klimek M, et al. Reversal of rocuronium-induced (1.2mg kg-1) profound neuromuscular block by accidental high dose of sugammadex (40 mg kg-1). Br J Anaesth 2007 May; 98(5): 624–7PubMedCrossRefGoogle Scholar
  65. 65.
    European Medicines Agency. European Public Assessment Report for Bridion (sugammadex): scientific discussion [online]. Available from URL: http://www.emea.europa.eu/humandocs/PDFs/EPAR/bridion/H-885-en6.pdf [Accessed 2008 Oct 1]
  66. 66.
    Plaud B, van Heumen E, Zwiers A. Sugammadex is well tolerated for the reversal of rocuronium- or vecuronium-induced neuromuscular blockade in a pooled analysis of adverse events in 10 placebo-controlled trials [abstract no. 9AP3-3]. Eur J Anaesthesiol 2008; 25 Suppl. 44: 9AP3–3. Plus poster presented at the 2008 Congress of the European Society of Anaesthesiology; 2008 May 31–Jun 3; CopenhagenGoogle Scholar
  67. 67.
    Mattila K, Toivonen J, Janhunen L, et al. Postdischarge symptoms after ambulatory surgery: first-week incidence, intensity, and risk factors. Anesth Analg 2005 Dec; 101(6): 1643–50PubMedCrossRefGoogle Scholar
  68. 68.
    Weiser TG, Regenbogen SE, Thompson KD, et al. An estimation of the global volume of surgery: a modelling strategy based on available data. Lancet 2008 Jul 12; 372(9633): 139–44PubMedCrossRefGoogle Scholar
  69. 69.
    Donati F. Sugammadex: a cyclodextrin to reverse neuromuscular blockade in anaesthesia. Expert Opin Pharmac-other 2008 May; 9(8): 1375–86CrossRefGoogle Scholar
  70. 70.
    Eriksson LI. Evidence-based practice and neuromuscular monitoring: it’s time for routine quantitative assessment. Anesthesiology 2003 May; 98(5): 1037–9PubMedCrossRefGoogle Scholar
  71. 71.
    Debaene B, Plaud B, Dilly M-P, et al. Residual paralysis in the PACU after a single intubating dose of nondepolarizing muscle relaxant with an intermediate duration of action. Anesthesiology 2003 May; 98(5): 1042–8PubMedCrossRefGoogle Scholar
  72. 72.
    Murphy GS. Residual neuromuscular blockade: incidence, assessment, and relevance in the postoperative period. Minerva Anestesiol 2006 Mar; 72(3): 97–109PubMedGoogle Scholar
  73. 73.
    Hunter JM, Flockton EA. The doughnut and the hole: a new pharmacological concept for anaesthetists. Br J Anaesth 2006 Aug; 97(2): 123–6PubMedCrossRefGoogle Scholar
  74. 74.
    Miller RD. Antagonism of neuromuscular blockade. Anesthesiology 1976 Apr; 44(4): 318–29PubMedCrossRefGoogle Scholar
  75. 75.
    Naguib M, Kopman AF, Ensor JE. Neuromuscular monitoring and postoperative residual curarization: a meta-analysis. Br J Anaesth 2007 Mar; 98(3): 302–16PubMedCrossRefGoogle Scholar
  76. 76.
    Murphy GS, Szokol JW, Marymont JH, et al. Residual neuromuscular blockade and critical respiratory events in the post-anesthesia care unit. Anesth Analg 2008 Jul; 107(1): 130–7PubMedCrossRefGoogle Scholar
  77. 77.
    Arbous MS, Meursing AEE, van Kleef JW, et al. Impact of anesthesia management characteristics on severe morbidity and mortality. Anesthesiology 2005 Feb; 102(2): 257–68PubMedCrossRefGoogle Scholar
  78. 78.
    Kopman AF, Eikermann M. Antagonism of non-depolarising neuromuscular block: current practice. Anaesthesia 2009 Mar; 64 Suppl. 1: 22–30PubMedCrossRefGoogle Scholar
  79. 79.
    Naguib M. Sugammadex: another milestone in clinical neuromuscular pharmacology. Anesth Analg 2007 Mar; 104(3): 575–81PubMedCrossRefGoogle Scholar
  80. 80.
    Harris AM, Welliver M, Redfern R, et al. Orthopaedic surgery implications of a novel encapsulation process that improves neuromuscular blockade and reversal. Internet J Orthop Surg 2007; 7(2): el–12Google Scholar
  81. 81.
    Reid JE, Breslin DS, Mirakhur RK, et al. Neostigmine antagonism of rocuronium block during anesthesia with sevoflurane, isoflurane or propofol. Can J Anesth 2001 Apr; 48(4): 351–5PubMedCrossRefGoogle Scholar
  82. 82.
    Mirakhur RK. Sugammadex in clinical practice. Anaesthesia 2009 Mar; 64 Suppl. 1: 45–54PubMedCrossRefGoogle Scholar
  83. 83.
    Duvaldestin P, Kuizenga K, Kjaer CC, et al. Sugammadex achieves fast recovery from profound neuromuscular blockade induced by rocuronium or vecuronium: a dose-response study [abstract no. 9AP7-3]. Eur J Anaesthesiol 2007 Jun; 24: 123. Plus poster presented at the 2007 Congress of the European Society of Anaesthesiology; 2007 Jun 9–12; MunichCrossRefGoogle Scholar
  84. 84.
    Levano S, Ginz H, Siegemund M, et al. Genotyping the butyrylcholinesterase in patients with prolonged neuromuscular block after succinylcholine. Anesthesiology 2005 Mar; 102(3): 531–5PubMedCrossRefGoogle Scholar
  85. 85.
    Brull SJ. Patient safety revisited: reliability is paramount. Anesth Analg 2009 Mar; 108(3): 702–3PubMedCrossRefGoogle Scholar
  86. 86.
    White PF, Tufanogullari B, Sacan O, et al. The effect of residual neuromuscular blockade on the speed of reversal with sugammadex. Anesth Analg 2009 Mar; 108(3): 846–51PubMedCrossRefGoogle Scholar
  87. 87.
    Perry JJ, Lees JS, Sillberg VA, et al. Rocuronium versus succinylcholine for rapid sequence induction intubation. Cochrane Database Syst Rev 2008 Apr 16; 16(2): CD002788Google Scholar
  88. 88.
    Zhang B, Menzin J, Tran MH, et al. The potential savings in operating room time associated with the use of sugammadex to reverse selected neuromuscular blocking agents: findings from a hospital efficiency model [abstract no. PHC9]. Value Health 2008 May–Jun; 11(3): A244CrossRefGoogle Scholar
  89. 89.
    Schering-Plough Corp. US FDA issues action letter for sugammadex [online]. Available from URL: http://www.schering-plough.com/schering_plough/news/release.jsp?releaseID=1182475 [Accessed 2008 Aug 20]

Copyright information

© Adis Data Information BV 2009

Authors and Affiliations

  1. 1.Wolters Kluwer Health ¦ AdisMairangi Bay, North Shore, AucklandNew Zealand
  2. 2.Wolters Kluwer HealthPhiladelphiaUSA

Personalised recommendations