Dose-response study of sugammadex sodium on reversing neuromuscular block of rocuronium in patients with abnormal liver function

doi:10.11958/20212847

Abstract

Abstract:

Objective To investigate the dose-effect relationship of sugammadex sodium on reversing neuromuscular block of rocuronium in patients with liver dysfunction. Methods Eighty patients who underwent elective partial hepatectomy were selected. According to the Child-Pugh classification, patients were divided into the experimental group (Child-Pugh class A) and the control group (normal liver function), with 40 cases in each group. Sugammadex sodium was intravenously injected immediately after the operation at the time of 1-2 times of single-stimulated muscle twitch count (PTC) after tonic stimulation. Dixon sequential method was used to adjust the dosage of sugammadex sodium in both groups, and the first patient was intravenously injected with the initial dose of sugammadex sodium 4 mg/kg, with a dose gradient of 0.5 mg/kg. The ED₉₅ of sugammadex sodium was calculated. Results The intraoperative dose of rocuronium bromide was significantly lower in the experimental group than that in the control group (P<0.05). The maximum dosage of sugammadex sodium was 5.5 mg/kg in the experimental group, and the maximum dosage of sugammadex was 4.5 mg/kg in the control group. The Probit model formula of the control group was Probit(P)=-10.891+3.009×dose, and the Probit model formula of the experimental group was Probit(P)=-8.095+1.864×dose. The ED₉₅ of sugammadex sodium for reversing rocuronium bromide neuromuscular block was 4.167 mg/kg in patients of the control group (95%CI: 3.824-4.509 mg/kg). The ED₉₅ of sugammadex sodium for reversing neuromuscular blockade in patients of the experimental group was 5.224 mg/kg (95%CI: 4.577-5.872 mg/kg). Conclusion Compared with patients with normal liver function, patients with abnormal liver function require a larger dose of sugammadex to reverse the neuromuscular blockade of rocuronium bromide, with an ED₉₅ of 5.224 mg/kg.

Key words: hepatic insufficiency, sugammadex sodium, rocuronium, 95% effective dose

CLC Number:

R762

Figures/Tables 6

Tab.1 Comparison of general information between the two groups of patients

组别	n	年龄（岁）	性别（男/女）	BMI（kg/m²）	手术时间（min）	罗库溴铵（mg）	血肌酐（μmol/L）	尿素氮（mmol/L）
对照组	40	56.8±5.1	28/12	22.7±2.2	98±15	57±25	82.7±9.7	4.8±1.0
试验组	40	57.3±5.5	24/16	22.3±2.5	104±18	47±16	86.4±10.2	5.1±0.9
t或χ²		0.422	0.879	0.760	1.620	2.131^＊	1.662	1.410

Fig.1 Comparison of success rate of sugammadex sodium reversing rocuronium nerve block between the different concentrations of sugammadex sodium

Fig.2 Recovery of neuromuscular block in patients of the treatment group

Fig.3 Recovery of neuromuscular block in patients of the control group

Fig.4 Dose response relationship diagram of sugammadex sodium in the treatment group

Fig.5 Dose response relationship diagram of sugammadex sodium in the control group

References 20

[1]	COUTO M, NUNES C, VIDE S, et al. Rocuronium continuous infusion for profound neuromuscular blockade:A systematic review and meta-analysis[J]. Clin Neuropharmacol, 2019, 42(6):203-210. doi:10.1097/WNF.0000000000000366.
[2]	COUTO M, COUTO J G, NUNES C S, et al. Systematic review on rocuronium continuous infusion for deep neuromuscular blockade[J]. Curr Rev Clin Exp Pharmacol, 2021, 16(1):64-72. doi:10.2174/1574884714666191120144331.
[3]	KHALIL M, D'HONNEUR G, DUVALDESTIN P, et al. Pharmacokinetics and pharmacodynamics of rocuronium in patients with cirrhosis[J]. Anesthesiology, 1994, 80(6):1241-1247. doi:10.1097/00000542-199406000-00011.
[4]	邬子林, 佘守章, 许立新, 等. 腹部手术中慢性肝功能不全病人罗库溴铵的药效学[J]. 中华麻醉学杂志, 2005, 25(9):653-656.
	WU Z L, YU S Z, XU L X, et al. Pharmacodynamics of rocuronium in patients with chronic liver dysfunction[J]. Chin J Anesthesiol, 2005, 25(9):653-656. doi:10.3760/j.issn:0254-1416.2005.09.003.
[5]	HUNTER J M. Reversal of neuromuscular block[J]. BJA Educ, 2020, 20(8):259-265. doi:10.1016/j.bjae.2020.03.008.
[6]	LEE H Y, JUNG K T. Advantages and pitfalls of clinical application of sugammadex[J]. Anesth Pain Med(Seoul), 2020, 15(3):259-268. doi:10.17085/apm.19099.
[7]	KOPMAN A F. Neuromuscular monitoring: Old issues,new controversies[J]. J Crit Care, 2009, 24(1):11-20. doi:10.1016/j.jcrc.2008.02.008.
[8]	SHIN S, HAN D W, LEE H S, et al. Elderly patients require higher doses of sugammadex for rapid recovery from deep neuromuscular block[J]. Basic Clin Pharmacol Toxicol, 2016, 118(6):462-467. doi:10.1111/bcpt.12507.
[9]	TAKAZAWA T, YAMAURA K, HARA T, et al. Practical guidelines for the response to perioperative anaphylaxis[J]. J Anesth, 2021, 35(6):778-793. doi:10.1007/s00540-021-03005-8.
[10]	李友清, 郭曲练. 肝功能障碍病人对罗库溴铵肌松时效的影响[J]. 中华麻醉学杂志, 2003, 23(11):816-818.
	LI Y Q, GUO Q L. Neuromuscular blocking effect of rocuronium in patients with liver dysfunction[J]. Chin J Anesthesiol, 2003, 23(11):816-818. doi:10.3760/j.issn:0254-1416.2003.11.004.
[11]	MAGORIAN T, WOOD P, CALDWELL J, et al. The pharmacokinetics and neuromuscular effects of rocuronium bromide in patients with liver disease[J]. Anesth Analg, 1995, 80(4):754-759. doi:10.1097/00000539-199504000-00018.
[12]	VAN MIERT M M, EASTWOOD N B, BOYD A H, et al. The pharmacokinetics and pharmacodynamics of rocuronium in patients with hepatic cirrhosis[J]. Br J Clin Pharmacol, 1997, 44(2):139-144. doi:10.1046/j.1365-2125.1997.00653.x.
[13]	ANZENBACHEROVA E, SPICAKOVA A, JOUROVA L, et al. Interaction of rocuronium with human liver cytochromes P450[J]. J Pharmacol Sci, 2015, 127(2):190-195. doi:10.1016/j.jphs.2014. 12.006.
[14]	KEATING G M. Sugammadex: A review of neuromuscular blockade reversal[J]. Drugs, 2016, 76(10):1041-1052. doi:10.1007/s40265-016-0604-1.
[15]	BATISTAKI C, MATSOTA P, KALIMERIS K, et al. Sugammadex antagonising rocuronium in three patients with liver dysfunction undergoing transjugular intrahepatic portosystemic shunt[J]. Anaesth Intensive Care, 2012, 40(3):556-557.
[16]	ABDULATIF M, LOTFY M, MOUSA M, et al. Sugammadex antagonism of rocuronium-induced neuromuscular blockade in patients with liver cirrhosis undergoing liver resection: A randomized controlled study[J]. Minerva Anestesiol, 2018, 84(8):929-937. doi:10.23736/S0375-9393.18.12217-6.
[17]	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[J]. Acta Anaesthesiol Taiwan, 2014, 52(2):54-58. doi:10.1016/j.aat.2014.04.007.
[18]	CRAIG R G, HUNTER J M. Neuromuscular blocking drugs and their antagonists in patients with organ disease[J]. Anaesthesia, 2009, 64 Suppl 1:55-65. doi:10.1111/j.1365-2044.2008.05871.x.
[19]	ARSLAN B, SAHIN T, OZDOGAN H. Sugammadex and anaphylaxis: An analysis of 33 published cases[J]. J Anaesthesiol Clin Pharmacol, 2021, 37(2):153-159. doi:10.4103/joacp.JOACP_383_19.
[20]	BURBRIDGE M A. Incidence of anaphylaxis to sugammadex in a single-center cohort of 19,821 patients[J]. Anesth Analg, 2021, 132(1):93-97. doi:10.1213/ANE.0000000000004752.