Influence of methylprednisolone on the reversal time of sugammadex: a randomized clinical trial
Influência da metilprednisolona no tempo de reversão do sugammadex: estudo clínico randomizado
Merve Hayriye Kocaoğlu, Başak Ceyda Meço, Menekşe Özçelik, Yeşim Batislam
Abstract
Background and objectives
Sugammadex is a modified gamma-cyclodextrin that reverses the effects of aminosteroidal neuromuscular blocking agents. Likewise, some steroid molecules, such as toremifene, fusidic acid, and flucloxacillin, can also be encapsulated by sugammadex. Methylprednisolone, which is a synthetic steroid used commonly for airway oedema prophylaxis, can also be encapsulated by sugammadex. The objective of this study was to compare the recovery times of sugammadex for reversing rocuronium-induced moderate neuromuscular blockade in those who received intraoperative 1 mgkg−1 methylprednisolone or saline.
Method
This single-centered, randomized, controlled, prospective study included 162 adult patients undergoing elective ear-nose-throat procedures (aged from 18–65, an ASA physical status I-II, a BMI less than 30 kgm−2, and not taking steroid drug medication) with propofol, remifentanyl, rocuronium and sevoflurane. Neuromuscular monitoring was performed using calibrated acceleromyography. The Control Group (Group C) received 5 mL of saline, while the Methylprednisolone Group (Group M) received 1 mg.kg−1 of methylprednisolone in 5 mL of saline just after induction. After the completion of surgery, regarding the TOF count, two reappeared spontaneously and 2 mg.kg−1 sugammadex was administered to all patients. Recovery of the TOF ratio to 0.9 was recorded for both groups, and the estimated recovery time to reach a TOF ratio (TOFr) of 0.9 was the primary outcome of the study.
Results
Median time to TOFr = 0.9 was for 130.00 s (range of 29–330) for Group C and 181.00s (100–420) for Group M (p < 0.001). The differences between the two groups were statistically significant.
Conclusion
When using 2 mg.kg−1 of sugammadex to reverse rocuronium-induced neuromuscular blockade in patients who received 1 mg.kg−1 of intraoperative methylprednisolone, demonstrated delayed recovery times.
Keywords
Resumo
Justificativa e objetivos
Sugammadex é uma gama-ciclodextrina modificada que reverte os efeitos de agentes de bloqueio neuromuscular aminoesteroides. Da mesma forma, algumas moléculas esteroides, como toremifene, ácido fusídico e flucloxacilina, podem ser encapsulados pelo sugammadex. A metilprednisolona, esteroide sintético usado geralmente para a profilaxia de edema de vias aéreas, também pode ser encapsulada pelo sugammadex. O objetivo do estudo foi comparar os tempos de recuperação do sugammadex na reversão de bloqueio neuromuscular moderado induzido pelo rocurônio em pacientes em que foi administrado 1mgkg−1 de metilprednisolona ou solução salina no período intraoperatório.
Método
Este estudo prospectivo, randomizado, controlado, unicêntrico incluiu 162 pacientes adultos (idades de 18-65, ASA I-II, IMC abaixo de 30 kgm−2, e não usando medicação esteroide) submetidos à anestesia geral para procedimento eletivo de otorrinolaringologia com propofol, remifentanil, rocurônio e sevoflurano. A monitorização neuromuscular foi realizada usando aceleromiógrafo calibrado. O grupo controle (Grupo C) recebeu 5 mL de solução salina, enquanto o grupo metilprednisolona (Grupo M) recebeu 1 mg.kg−1 de metilprednisolona em 5 mL de solução salina logo após a indução. Ao término da cirurgia, em relação à contagem do número de respostas à sequência de quatro estímulos (TOFc), dois pacientes mostraram recuperação espontânea e todos os pacientes receberam 2 mg.kg−1 de sugammadex. A recuperação da razão T4/T1 (TOFr) para 0,9 foi registrada nos dois grupos, e o desfecho primário do estudo foi o tempo estimado de recuperação, momento em que a razão TOFr alcançou o valor de 0,9 (TOFr = 0.9).
Resultados
O tempo mediano para TOFr = 0,9 foi 130 s (29–330) para o Grupo C e 181s (100–420) para o Grupo M (p < 0,001). As diferenças entre os dois grupos foi estatisticamente significante.
Conclusões
Pacientes que receberam 1 mg.kg−1 de metilprednisolona no intraoperatório apresentaram tempo de recuperação mais prolongado após o uso de 2 mg.kg−1 de sugammadex para reverter o bloqueio neuromuscular induzido pelo rocurônio.
Palavras-chave
References
1 L.P. Fortier, D. McKeen, K. Turner, et al. The RECITE Study: a Canadian prospective, multicenter study of the incidence and severity of residual neuromuscular blockade Anesth Analg, 121 (2015), pp. 366-372
2 M. Naguib, A.F. Kopman, J.E. Ensor Neuromuscular monitoring and postoperative residual curarization: a meta-analysis Br J Anaesth, 98 (2007), pp. 302-316
3 M. Grosse-Sundrup, J. Henneman, W. Sandberg, et al. Intermediate acting non-depolarizing neuromuscular blocking agents and risk of postoperative respiratory complications: prospective propensity score matched cohort study BMJ, 345 (2012), p. e6329
4 H. Berg, J. Roed, J. Viby-Mogensen, et al. Residual neuromuscular block is a risk factor for postoperative pulmonary complications. A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium Acta Anaesthesiol Scand, 41 (1997), pp. 1095-1103
5 T. Fuchs-Buder, R. Nemes, D. Schmartz Residual neuromuscular blockade: management and impact on postoperative outcome Curr Opin Anaesthesiol, 29 (2016), pp. 662-667
6 G. Murphy, J. Szokol, J. Marymont, et al. Residual neuromuscular blockade and critical respiratory events in the postanesthesia care unit Anesth Analg, 107 (2008), pp. 130-137
7 A. Bom, M. Bradley, K. Cameron, et al. A novel concept of reversing neuromuscular block: chemical encapsulation of rocuronium bromide by a cyclodextrine-based synthetic host Angew Chem Int Ed Engl, 41 (2002), pp. 266-270
8 B. Brueckmann, N. Sasaki, P. Grobara, et al. Effects of sugammadex on incidence of postoperative residual neuromuscular blockade: a randomized, controlled study Br J Anaesth, 115 (2015), pp. 743-751
9 T. Fuchs-Buder, C. Meistelman, J. Raft Sugammadex: clinical development and practical use Korean J Anesthesiol, 65 (2013), pp. 495-500
10 G. Geldner, M. Niskanen, P. Laurila, et al. A randomised controlled trial comparing sugammadex and neostigmine at different depths of neuromuscular blockade in patients undergoing laparoscopic surgery Anaesthesia, 67 (2012), pp. 991-998
11 M. Zhang Drug-specific cyclodextrins: the future of rapid neuromuscular block reversal Drugs Futur, 28 (2003), pp. 347-354
12 A. Akha, J. Rosa, J. Jahr, et al. Sugammadex: cyclodextrines, development of selective binding agents, pharmacology, clinical development, and future directions Anesthesiol Clin, 28 (2010), pp. 691-708
13 P. Peeters, P. Passier, J. Smeets, et al. Sugammadex is cleared rapidly and primarily unchanged via renal excretion Biopharm Drug Dispos, 32 (2011), pp. 159-167
14 K. Suy, K. Morias, G. Cammu, et al. Effective reversal of moderate rocuronium- or vecuronium-induced neuromuscular block with sugammadex, a selective relaxant binding agent Anesthesiology, 106 (2007), pp. 283-288
15 A. Abrishami, J. Ho, J. Wong, et al. Sugammadex, a selective reversal medication for preventing postoperative residual neuromuscular blockade Cochrane Database Syst Rev (2009) CD007362
16 D. Karalapillai, M. Kaufman, L. Weinberg, et al. Sugammadex Crit Care Resusc, 15 (2013), pp. 57-63
17 M. Shields, M. Giovanelli, R. Mirakhur, et al. Org 25969 (sugammadex), a selective relaxant binding agent for antagonism of prolonged rocuronium-induced neuromuscular block Br J Anaesth, 96 (2006), pp. 36-43
18 A. Srivastava, J.M. Hunter Reversal of neuromuscular block Br J Anaesth, 103 (2009), pp. 115-129
19 Y. Ustun, O. Erdogan, E. Esen, et al. Comparison of the effects of 2 doses of methylprednisolone on pain, swelling, and trismus after third molar surgery Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 96 (2003), pp. 535-539
19 C. Höhne Postoperative nausea and vomiting in pediatric anesthesia Curr Opin Anaesthesiol, 27 (2014), pp. 303-308
21 L. Romundstad, H. Breivik, H. Roald, et al. Methylprednisolone reduces pain, emesis, and fatigue after breast augmantation surgery: a single-dose, randomized, parallel-group study with mehylprednisolone 125 mg, parecoxib 40 mg, and placebo Anesth Analg, 102 (2006), pp. 418-425
22 R.J. Roberts, S.M. Welch, J.W. Devlin Corticosteroids for prevention of postextubation laryngeal edema in adults Ann Pharmacother, 42 (2008), pp. 686-691
23 S.M. Bagshaw, A. Delaney, C. Farrell, et al. Best evidence in critical care medicine. Steroids to prevent post-extubation airway obstruction in adult critically ill patients Can J Anesth, 55 (2008), pp. 382-385
24 W.A. Pluijms, W.N.K.A. Van Mook, B.H.J. Wittekamp, et al. Postextubation laryngeal edema and stridor resulting in respiratory failure in critically ill adult patients: updated review Crit Care, 19 (2015), pp. 1-9
25 B. François, E. Bellissant, V. Gissot, et al. 12-Hour pretreatment with methylprednisolone versus placebo for prevention of postextubation laryngeal oedema: a randomized double-blind trial Lancet, 369 (2007), pp. 1083-1089
26 E. Kaal, C. Vecht The management of brain edema in brain tumors Curr Opin Oncol, 16 (2004), pp. 593-600
27 K. Holte, H. Kehlet Perioperative single-dose glucocorticoid administration: pathophysiologic effects and clinical implications J Am Coll Surg, 195 (2002), pp. 694-711
28 A. Zwiers, M. Van Den Heuvel, J. Smeets, et al. Assessment of the potential for displacement interactions with sugammadex: a pharmacokinetic–pharmacodynamic modelling approach Clin Drug Investig, 31 (2011), pp. 101-111
29 K. Rezonja, M. Sostaric, G. Vidmar, et al. Dexamethasone produces dose-dependent inhibition of sugammadex reversal in in vitro innervated primary human muscle cells Anesth Analg, 118 (2014), pp. 755-763
30 T. Fuchs-Buder, C. Cladius, L. Skovgaard, et al. Good clinical research practice in pharmacodynamic studies of neuromuscular blocking agents II: the Stockholm revision Acta Anaesthesiol Scand, 51 (2007), pp. 789-808
31 K. Rezonja, P. Lorenzon, T. Mars Opposing effects of dexamethasone, agrin and sugammadex on functional innervation and constitutive secretion of IL-6 in in vitro innervated primary human muscle cells Neurosci Lett, 549 (2013), pp. 186-190
32 K. Rezonja, T. Mars, A. Jerin, et al. Dexamethasone does not diminish sugammadex reversal of neuromuscular block – clinical study in surgical patients undergoing general anesthesia BMC Anesthesiol, 16 (2016), pp. 1-10
33 P. Buonanno, A. Laiola, C. Palumbo, et al. Dexamethasone does not inhibit sugammadex reversal after rocuronium-induced neuromuscular block Anesth Analg, 122 (2016), pp. 1826-1830
34 E. Gulec, E. Biricik, M. Turktan, et al. The effect of intravenous dexamethasone on sugammadex reversal time in children undergoing adenotonsillectomy Anesth Analg, 122 (2016), pp. 1147-1152
35 S. Soltész, T. Mencke, C. Mey, et al. Influence of a continuous prednisolone medication on the time course of neuromuscular block of atracurium in patients with chronic inflammatory bowel disease Br J Anaesth, 100 (2008), pp. 798-802
36 S. Soltész, P. Fraisl, K. Noé, et al. Dexamethasone decreases the duration of rocuronium-induced neuromuscular block: a randomised controlled study Eur J Anaesthesiol, 31 (2014), pp. 417-422
37 W. Geng, Y. Nie, S. Huang Effects of methylprednisolone on the duration of rocuronium-induced neuromuscular block Medicine (Baltimore), 96 (2017), pp. 1-5
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