Anesth Pain Med.  2024 Oct;19(4):269-279. 10.17085/apm.24092.

Sugammadex for our little ones: a brief narrative review

• Lee S
• Chung W

• KMID: 2563569
• DOI: http://doi.org/10.17085/apm.24092

Abstract

Sugammadex, the first noncompetitive antagonist developed for the reversal of neuromuscular blockade (NMB), is one of the few drugs that has revolutionized anesthetic practice. However, the use of sugammadex for children between the ages of 2 and 17 years has only recently been approved and is currently not approved for children under the age of 2 years. Although the precision and reliability of reversal of NMB with sugammadex are of great benefit in pediatric anesthesia, several important questions remain regarding its use in our youngest patients. In this brief narrative review, we aim to provide an overview of the key considerations and potential challenges that anesthesiologists often face when using sugammadex in pediatric patients.

Keyword

Bradycardia; Hypersensitivity; Infant; Neostigmine; Neuromuscular blocking agent; Newborn; Pediatrics; Sugammadex

Reference

1. Nag K, Singh DR, Shetti AN, Kumar H, Sivashanmugam T, Parthasarathy S. Sugammadex: A revolutionary drug in neuromuscular pharmacolog. Anesth Essays Res. 2013; 7:302–6.

2. Lorrain PE, Schmartz D, Fuchs-Buder T. Neostigmine: mechanism of action, dosing, and factors determining adequacy of recovery following administration. Curr Anesthesiol Rep. 2018; 8:145–9.

3. Lang B, Han L, Zeng L, Zhang Q, Chen S, Huang L, et al. Efficacy and safety of sugammadex for neuromuscular blockade reversal in pediatric patients: an updated meta-analysis of randomized controlled trials with trial sequential analysis. BMC Pediatr. 2022; 22:295.

4. Chhabra R, Gupta R, Gupta LK. Sugammadex versus neostigmine for reversal of neuromuscular blockade in adults and children: a systematic review and meta-analysis of randomized controlled trials. Curr Drug Saf. 2024; 19:33–43.

5. Lee W. The potential risks of sugammadex. Anesth Pain Med. 2019; 14:117–22.

6. Lee C, Jahr JS, Candiotti KA, Warriner B, Zornow MH, Naguib M. Reversal of profound neuromuscular block by sugammadex administered three minutes after rocuronium: a comparison with spontaneous recovery from succinylcholine. Anesthesiology. 2009; 110:1020–5.

7. Ji SH, Huh KY, Oh J, Jeong HJ, Jang YE, Kim EH, et al. Conventional reversal of rocuronium-induced neuromuscular blockade by sugammadex in Korean children: pharmacokinetics, efficacy, and safety analyses. Front Pharmacol. 2023; 14:1127932.

8. Wołoszczuk-Gębicka B, Zawadzka-Głos L, Lenarczyk J, Sitkowska BD, Rzewnicka I. Two cases of the “cannot ventilate, cannot intubate” scenario in children in view of recent recommendations. Anaesthesiol Intensive Ther. 2014; 46:88–91.

9. Wakimoto M, Burrier C, Tobias JD. Sugammadex for rapid intraoperative reversal of neuromuscular blockade in a neonate. J Med Cases. 2018; 9:400–2.

10. Ji SH, Huh KY, Oh J, Jeong HJ, Jang YE, Kim EH, et al. Reversal of rocuronium‐induced intense neuromuscular blockade by sugammadex in Korean children: A pharmacokinetic and pharmacodynamic analysis. Clin Transl Sci. 2023; 16:92–103.

11. Krishna SG, Bryant JF, Tobias JD. Management of the difficult airway in the pediatric patient. J Pediatr Intensive Care. 2018; 7:115–25.

12. Raval AD, Anupindi VR, Ferrufino CP, Arper DL, Bash LD, Brull SJ. Epidemiology and outcomes of residual neuromuscular blockade: a systematic review of observational studies. J Clin Anesth. 2020; 66:109962.

13. Shimizu T, Toda Y, Shimizu K, Iwasaki T, Kanazawa T, Ishii N, et al. Increase in serum vecuronium concentration following sugammadex administration in a pediatric patient after prolonged sedation. Masui. 2013; 62:1225–9.

14. Iwasaki H, Takahoko K, Otomo S, Sasakawa T, Kunisawa T, Iwasaki H. A temporary decrease in twitch response following reversal of rocuronium-induced neuromuscular block with a small dose of sugammadex in a pediatric patient. J Anesth. 2014; 28:288–90.

15. Carollo DS, White WM. Postoperative recurarization in a pediatric patient after sugammadex reversal of rocuronium-induced neuromuscular blockade: a case report. A A Pract. 2019; 13:204–5.

16. Lorinc AN, Lawson KC, Niconchuk JA, Modes KB, Moore JD, Brenn BR. Residual weakness and recurarization after sugammadex administration in pediatric patients: a case series. A A Pract. 2020; 14:e01225.

17. Cates AC, Freundlich RE, Clifton JC, Lorinc AN. Analysis of the factors contributing to residual weakness after sugammadex administration in pediatric patients under 2 years of age. Paediatr Anaesth. 2024; 34:28–34.

18. He J, He H, Li X, Sun M, Lai Z, Xu B. Required dose of sugammadex or neostigmine for reversal of vecuronium-induced shallow residual neuromuscular block at a train-of-four ratio of 0.3. Clin Transl Sci. 2022; 15:234–43.

19. Min K, Bondiskey P, Schulz V, Woo T, Assaid C, Yu W, et al. Hypersensitivity incidence after sugammadex administration in healthy subjects: a randomised controlled trial. Br J Anaesth. 2018; 121:749–57.

20. Zecic F, Smart MH, Abbey TC, Pazhempallil A, Korban C. Sugammadex-induced anaphylactic reaction: a systematic review. J Anaesthesiol Clin Pharmacol. 2022; 38:360–70.

21. Miyazaki Y, Sunaga H, Kida K, Hobo S, Inoue N, Muto M, et al. Incidence of anaphylaxis associated with sugammadex. Anesth Analg. 2018; 126:1505–8.

22. Orihara M, Takazawa T, Horiuchi T, Sakamoto S, Nagumo K, Tomita Y, et al. Comparison of incidence of anaphylaxis between sugammadex and neostigmine: a retrospective multicentre observational study. Br J Anaesth. 2020; 124:154–63.

23. Tsur A, Kalansky A. Hypersensitivity associated with sugammadex administration: a systematic review. Anaesthesia. 2014; 69:1251–7.

24. Arslan B, Sahin T, Ozdogan H. Sugammadex and anaphylaxis: an analysis of 33 published cases. J Anaesthesiol Clin Pharmacol. 2021; 37:153–9.

25. Banoub R, Alalade E, Bryant J, Winch P, Tobias JD. Allergic reactions to Sugammadex: A case series and review of the literature. J Pediatr Pharmacol Ther. 2023; 28:374–9.

26. Zhou S, Hu H, Ru J. Efficacy and safety of sugammadex sodium in reversing rocuronium-induced neuromuscular blockade in children: An updated systematic review and meta-analysis. Heliyon. 2023; 9:e18356.

27. Alsuhebani M, Sims T, Hansen JK, Hakim M, Walia H, Miller R, et al. Heart rate changes following the administration of sugammadex in children: a prospective, observational study. J Anesth. 2020; 34:238–42.

28. Carvalho EVG, Caldas SMC, Costa DFPPMd, Gomes CMGP. Bradycardia in a pediatric population after sugammadex administration: case series. Braz J Anesthesiol. 2022; 73:101–3.

29. Bhavani S. Severe bradycardia and asystole after sugammadex. Br J Anaesth. 2018; 121:95–6.

30. King A, Naguib A, Tobias JD. Bradycardia in a pediatric heart transplant recipient: is it the sugammadex? J Pediatr Pharmacol Ther. 2017; 22:378–81.

31. Vaswani ZG, Smith SM, Zapata A, Gottlieb EA, Sheeran PW. Bradycardic arrest in a child with complex congenital heart disease due to sugammadex administration. J Pediatr Pharmacol Ther. 2023; 28:667–70.

32. Arends J, Hubbard R, Shafy SZ, Hakim M, Kim SS, Tumin D, et al. Heart rate changes following the administration of sugammadex to infants and children with comorbid cardiac, cardiovascular, and congenital heart diseases. Cardiol Res. 2020; 11:274.

33. McGuire B, Dalton A. Sugammadex, airway obstruction, and drifting across the ethical divide: a personal account. Anaesthesia. 2016; 71:487–92.

34. Kou K, Omae T, Wakabayashi S, Sakuraba S. A case in which a capnometer was useful for diagnosing laryngospasm following administration of sugammadex. JA Clin Rep. 2017; 3:41.

35. Greenaway S, Shah S, Dancey M. Sugammadex and laryngospasm. Anaesthesia. 2017; 72:412–3.

36. Suzuki M, Inagi T, Kikutani T, Mishima T, Bito H. Negative pressure pulmonary edema after reversing rocuronium-induced neuromuscular blockade by sugammadex. Case Rep Anesthesiol. 2014; 135032.

37. Lee JH, Lee JH, Lee MH, Cho HO, Park SE. Postoperative negative pressure pulmonary edema following repetitive laryngospasm even after reversal of neuromuscular blockade by sugammadex: a case report. Korean J Anesthesiol. 2017; 70:95–9.

38. Ikeda-Miyagawa Y, Kihara T, Matsuda R. Case of negative pressure pulmonary edema after administration of sugammadex under general anesthesia with laryngeal mask airway. Masui. 2014; 63:1362–5.

39. Wu TS, Tseng WC, Lai HC, Huang YH, Wu ZF. Sugammadex and laryngospasm. J Clin Anesth. 2019; 56:52.

40. Jain A, Batra J, Lamperti M, Doyle DJ. Succinylcholine rescue for sugammadex-induced laryngospasm. Comment on Br J Anaesth 2020; 125: 423–5. Br J Anaesth. 2021; 126:e58–9.

41. Kang E, Lee BC, Park JH, Lee SE, Kim SH, Oh D, et al. The relationship between the timing of sugammadex administration and the upper airway obstruction during awakening from anesthesia: A retrospective study. Medicina (Kaunas). 2021; 57:88.

42. Komasawa N, Nishihara I, Minami T. Relationship between timing of sugammadex administration and development of laryngospasm during recovery from anaesthesia when using supraglottic devices: a randomised clinical study. Eur J Anaesthesiol. 2016; 33:691–2.

43. Iwasaki H, Igarashi M, Namiki A, Omote K. Differential neuromuscular effects of vecuronium on the adductor and abductor laryngeal muscles and tibialis anterior muscle in dogs. Br J Anaesth. 1994; 72:321–3.

44. Ishibashi K, Kitamura Y, Kato S, Sugano M, Sakaguchi Y, Sato Y, et al. Changes in laryngeal airway patency in response to complete reversal of rocuronium-induced paralysis with sugammadex in small children with a supraglottic airway: protective effect of fentanyl? Br J Anaesth. 2020; 125:e158–e60.

45. Devoy T, Smith N. Sugammadex and oral contraceptives. Curr Opin Anaesthesiol. 2024; 37:338–43.

46. Devoy T, Hunter M, Smith N. A prospective observational study of the effects of sugammadex on peri‐operative oestrogen and progesterone levels in women who take hormonal contraception. Anaesthesia. 2023; 78:180–7.

47. Meakin GH. Neuromuscular blocking drugs in infants and children. Contin Educ Anaesth Crit Care Pain. 2007; 7:143–7.

48. Ruggiero A, Ariano A, Triarico S, Capozza MA, Ferrara P, Attinà G. Neonatal pharmacology and clinical implications. Drugs Context. 2019; 8:212608.

49. Cha YM, Faulk DJ. Management of neuromuscular block in pediatric patients—safety implications. Curr Anesthesiol Rep. 2022; 12:439–50.

50. Brown SES, Mentz G, Cassidy R, Wade M, Liu X, Zhong W, et al. Factors associated with decision to use and dosing of sugammadex in children: a retrospective cross-sectional observational study. Anesth Analg. 2024; doi: 10.1213/ANE.0000000000006831. [Epub ahead of print].

51. Franz AM, Chiem J, Martin LD, Rampersad S, Phillips J, Grigg EB. Case series of 331 cases of sugammadex compared to neostigmine in patients under 2 years of age. Paediatr Anaesth. 2019; 29:591–6.

52. Efune PN, Alex G, Mehta SD. Emergency sugammadex reversal in an 850-G premature infant: a case report. J Pediatr Pharmacol Ther. 2020; 26:107–10.

53. Cárdenas VHG, González FDM. Sugammadex in the neonatal patient. Rev Colomb Anestesiol. 2013; 41:171–4.

54. Carlos RV, Torres MLA, De Boer HD. Rocuronium and sugammadex in a 3 days old neonate for draining an ovarian cyst. Neuromuscular management and review of the literature. Rev Bras Anestesiol. 2016; 66:430–2.

55. Sarı S, Taşdemir B, Sözkısacık S, Gürsoy F. Side effects of sugammadex use in pediatric patients. J Clin Exp Invest. 2013; 44.

56. Alonso A, De Boer H, Booij L. Reversal of rocuronium-induced neuromuscular block by sugammadex in neonates: 10AP1-3. Eur J Anaesthesiol. 2014; 31:163.

57. Ozmete O, Bali C, Ergenoglu P, Andic C, Aribogan A. Anesthesia management and sugammadex experience in a neonate for Galen vein aneurysm. J Clin Anesth. 2016; 31:36–7.

58. Plaud B, Meretoja O, Hofmockel R, Raft J, Stoddart PA, Van Kuijk JH, et al. Reversal of rocuronium-induced neuromuscular blockade with sugammadex in pediatric and adult surgical patients. Anesthesiology. 2009; 110:284–94.

59. Benigni A, Maffioletti M, Spotti A, Benigni A, Locatelli B, Sonzogni V. Efficacy and safety of a sugammadex dose of 4 mg/kg in early reversal of a deep neuromuscular block rocuronium-induced in infants and children: a case series: 10AP2-10. Eur J Anaesthesiol. 2013; 30:161–2.

60. Saber HIES, Mousa SA, AbouRezk AR, Zaglool A. Recovery profile of sugammadex versus neostigmine in pediatric patients undergoing cardiac catheterization: a randomized double-blind study. Anesth Essays Res. 2021; 15:272–8.

61. Van Den Bersselaar LR, Snoeck MM, Gubbels M, Riazi S, Kamsteeg EJ, Jungbluth H, et al. Anaesthesia and neuromuscular disorders: what a neurologist needs to know. Pract Neurol. 2021; 21:12–24.

62. Van den Bersselaar LR, Heytens L, Silva HC, Reimann J, Tasca G, Díaz‐Cambronero Ó, et al. European Neuromuscular Centre consensus statement on anaesthesia in patients with neuromuscular disorders. Eur J Neurol. 2022; 29:3486–507.

63. Radkowski P, Suren L, Podhorodecka K, Harikumar S, Jamrozik N. A review on the anesthetic management of patients with neuromuscular diseases. Anesth Pain Med. 2023; 13:e132088.

64. Thilen SR, Weigel WA, Todd MM, Dutton RP, Lien CA, Grant SA, et al. 2023 American Society of Anesthesiologists practice guidelines for monitoring and antagonism of neuromuscular blockade: a report by the American Society of Anesthesiologists task force on neuromuscular blockade. Anesthesiology. 2023; 138:13–41.

65. Plaud B, Baillard C, Bourgain J-L, Bouroche G, Desplanque L, Devys JM, et al. Guidelines on muscle relaxants and reversal in anaesthesia. Anaesth Crit Care Pain Med. 2020; 39:125–42.

66. Gurunathan U, Kunju SM, Stanton LML. Use of sugammadex in patients with neuromuscular disorders: a systematic review of case reports. BMC Anesthesiol. 2019; 19:1–18.

67. Schneider A, Tramèr MR, Keli-Barcelos G, Elia N. Sugammadex and neuromuscular disease: a systematic review with assessment of reporting quality and content validity. Br J Anaesth. 2024; 133:752–8.

68. Kim JE, Chun HR. Rocuronium-induced neuromuscular block and sugammadex in pediatric patient with Duchenne muscular dystrophy: a case report. Medicine. 2017; 96:e6456.

69. De Boer HD, Van Esmond J, Booij LH, Driessen JJ. Reversal of rocuronium‐induced profound neuromuscular block by sugammadex in Duchenne muscular dystrophy. Paediatr Anaesth. 2009; 19:1226–8.

70. Takeda A, Kawamura M, Hamaya I, Kitamura H, Muto R, Mitono H. Case of anesthesia for thoracoscopic thymectomy in a pediatric patient with myasthenia gravis: reversal of rocuronium-induced neuromuscular blockade with sugammadex. Masui. 2012; 61:855–8.

71. Erbabacan E, Köksal GM, Şeker TB, Ekici B, Özcan R, Altindaş F. Anaesthesia management and use of sugammadex in a patient with Ullrich’s disease. Turk J Anaesthesiol Reanim. 2015; 43:356.

72. Pickard A, Lobo C, Stoddart PA. The effect of rocuronium and sugammadex on neuromuscular blockade in a child with congenital myotonic dystrophy type 1. Paediatr Anaesth. 2013; 23:871–3.

73. Li L, Jiang Y, Zhang W. Sugammadex for fast-track surgery in children undergoing cardiac surgery: a randomized controlled study. J Cardiothorac Vasc Anesth. 2021; 35:1388–92.