Reversal of neuromuscular block produced by local anaesthetics combined with pancuronium. Experimental study.

Main Article Content

Vanessa Henriques Carvalho Angélica Assunção Braga Franklin Sarmento Braga Fernando Eduardo Feres Junqueira Renata Muzzi Drummond Guilherme Litterio Benette



Justification and objectives: There are few clinical and experimental studies on the interaction between local anaesthetics and nondepolarising neuromuscular blocking agents and their effects on the neuromuscular junction. However, potentiation of these drugs has been observed when they are used simultaneously. The aim of this study was to evaluate in vitro the efficacy of neostigmine and 4-aminopyridine in the reversal of a neuromuscular block produced by pancuronium combined with different local anaesthetics.

Method: Rats were distributed in groups (n = 5), according to drug combinations: pancuronium + levobupivacaine and pancuronium + enantiomeric mixture. The concentrations of levobupivacaine, enantiomeric mixture and pancuronium were respectively 5µg.mL-1, 5µg.mL-1 and 2µg.mL-1. Neostigmine and 4-aminopyridine were used in concentrations of 2µg.mL-1 and 20µg.mL-1, respectively. The following parameters were evaluated: 1) degree of neuromuscular block obtained by a combination of pancuronium + levobupivacaine and pancuronium + enantiomeric mixture; 2) efficacy of neostigmine and 4-aminopyridine in the reversal of neuromuscular block produced by drug combinations.

Results and Conclusion: Neostigmine and 4-aminopyridine were effective at reversing neuromuscular block obtained by different drug combinations, and the block was partially and totally reversed with neostigmine and 4-aminopyridine, respectively.

Keywords: Local anaesthetics, neuromuscular junction, neuromuscular blocking drugs

Article Details

How to Cite
CARVALHO, Vanessa Henriques et al. Reversal of neuromuscular block produced by local anaesthetics combined with pancuronium. Experimental study.. Medical Research Archives, [S.l.], v. 6, n. 5, may 2018. ISSN 2375-1924. Available at: <>. Date accessed: 03 dec. 2023. doi:
Research Articles


1. Matsuo S, Rao DB, Chaudry I, Foldes FF. Interaction of muscle relaxants and local anesthetics at the neuromuscular junction. Anesth Analg 1978; 57(5):580-7.
2. Braga AF, Carvalho VH, Braga FS, Potério GM, Santos, FN. Evidence of pre-synaptic and postsynaptic action of local anesthetics in rats. Acta Cir Bras 2013; 28(11):774-7.
3. Carvalho VH, Braga AF, Braga FS, Loyola YC, Araújo DR, Mantovani M. The influence of lidocaine and racemic bupiva-caine on neuromuscular blockade produced by rocuronium. A study in rat phrenic nerve-diaphragm preparation. Acta Cir Bras 2009; 24(3):211-5.
4. Braga AF, Carvalho VH, Braga FS, Potério GM, Santos FN. Effect of ropiva-caine combined with pancuronium on neu-romuscular transmission and effectiveness of neostigmine and 4-aminopyridine for blockade reversal: experimental study. Rev Bras Anestesiol 2015;65(2):136-40.
5. Jones RK, Caldwell JE, Brull SJ, Soto RG. Reversal of profound rocuronium-induced blockade with sugammadex: a randomized comparison with neostigmine. Anesthesiology 2008;109:816-824.
6. Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Vender JS, et al. Residual Neuromuscular Block in the El-derly: Incidence and Clinical Implications. Anesthesiology 2015; 123(6):1322-36.
7. Carvalho VH, Braga AdeF, Braga FS, Potério GM, Santos FN, Junqueira FE. Association between levobupivacaine and pancuronium. Interference in neuromuscu-lar transmission and blockade in rats. Acta Cir Bras 2016; 31(7):486-9.
8. Gristwood R, Bardsley H, Baker H. Reduced cardiotoxicity of levobupivacaine compared with racemic bupivacaine (Mar-caine): new clinical evidence. Exp Opin.Invest Drugs 1994; 3:1208-1212.
9. Simonetti MPB. Contribuição da qui-ralidade na qualidade total na anestesia
regional (Cartas ao Editor). Rev Bras Anestesiol 1997a; 47: 86-88.
10. Stoelting RK, Hillier SC. Neuromus-cular blocking drugs. In: Stoelting RK, Hillier SC. Pharmacology & Phisiology in Anesthetic Practice. Philadelphia: Lippin-cott Williams Wilk, 2006b: 208-250.
11. Donati F. Neuromuscular Blocking Agents. In: Barash PG, Cullen BF, Stoel-ting RK, Cahalan MK, Stock MC; Ortega R. Clinical Anesthesia, 7th ed. Philadelphia Lippincot: Williams & Wilkins 2013: 523-560.
12. Bulbring E. Observation on the iso-lated phyrenic nerve-diaphragm prepara-tion of the rat. Br J Pharmacol 1946; 1:38-61.
13. Sahin SH, Colak A, Sezer A, Arar C, Sevdi S, Gunday I, et al. Effect of epidural levobupivacaine on recovery from vecuro-nium-induced neuromuscular block in pa-tients undergoing lower abdominal surgery. Anaesth Intensive Care 2011; 39:607-10.
14. Toft P, Kirkegaard Nielsen H, Seve-rinsen I, Helbo-Hansen HS. Effect of epi-durally administered bupivacaíne on atra-curium-induced neuromuscular blockade. Acta Anaesthesiol Scand 1990; 34:649-652.
15. de Assunção Braga Ade F, Carvalho VH, da Silva Braga FS, Potério GM, San-tos FN, Junqueira FE. Effect of 50% enan-tiomeric excess bupivacaine mixture com-bined with pancuronium on neuromuscular transmission in rat phrenic nerve-diaphragm preparation; a pilot study. In-dian J Anaesth 2015;59(11):701-5.
16. Yeh JZ, Oxford GS, Wu CH, Naraha-shi T. Interactions of aminopyridi-nes with potassium channels of squid axon mem-branes. Biophys J 1976; 16:77-81.
17. Ulbricht W, Wagner HH. Block of potassium channels of the nodal membrane by 4-aminopyridine and its partial removal on depolarization. Pfluger Arch1976;367:77-87.
18. Brazil OV, Fontana MD, Pavani NJ. Effect of 4-aminopyridine on the postsy-naptic action of polymyxin B. Eur J Phar-macol 1989; 159:47-51.
19. Harvey AL, Marshall IG. The actions of three diaminopyridines on the chick biventer cervicis muscle. Eur J Pharmacol 1977; 44:303-309.
20. Wu ZZ, Li DP, Chen SR, Pan HL. Aminopyridines potentiate synaptic and neuromuscular transmission by targeting the voltage-activated calcium channel beta subunit. J Biol Chem 2009; 25:36453-61.