Korean J Anesthesiol.  2011 Oct;61(4):320-326. 10.4097/kjae.2011.61.4.320.

The antagonistic effect of neostigmine on rocuronium-, clindamycin-, or both-induced neuromuscular blocking in the rat phrenic nerve-hemidiaphragm

• Kim SS
• Lee SI
• Chung CJ
• Lee SC

• KMID: 1766774
• DOI: http://doi.org/10.4097/kjae.2011.61.4.320

Abstract

BACKGROUND
Neostigmine augments clindamycin-induced neuromuscular block and antagonizes rocuronium-induced neuromuscular block; however, it remains unclear whether neostigmine enhances the neuromuscular blocking (NMB) that is caused by combinations of rocuronium and clindamycin. The intent of this study was to determine whether neostigmine potentiates the muscle relaxation that is induced by combinations of rocuronium and clindamycin and to estimate whether both clindamycin and rocuronium have synergistic actions on NMB.
METHODS
Forty-one left phrenic nerve-hemidiaphragms (from male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Three consecutive single twitches (ST, 0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained for each increase in concentration of rocuronium or clindamycin. The concentrations of rocuronium were cumulatively increased until an 80% to 90% reduction in ST was attained in the Krebs solutions pre-treated with 0 (n = 5), 0.1 (n = 1), 0.25 (n = 1), 0.5 (n = 4), or 1.0 (n = 1) mM clindamycin or with 0 (n = 4), 0.1 (n = 1), 0.5 (n = 5), 1.0 (n = 5), or 2.0 (n = 4) mM clindamycin in combination with 250 nM neostigmine, and so were the concentrations of clindamycin in the Krebs solutions pre-treated with 0 (n = 6) or 250 nM (n = 6) neostigmine.
RESULTS
Clindamycin increased the potency of rocuronium for ST and tetanic fade, irrespective of the presence of neostigmine. Neostigmine shifted the concentration-response curve of rocuronium to the right in the presence or absence of clindamycin. The interaction between rocuronium and clindamycin was synergistic when clindamycin concentrations were in excess of 0.5 mM, irrespective of the presence of neostigmine.
CONCLUSIONS
Neostigmine may partially antagonize the neuromuscular block that is induced by a combination of clindamycin and rocuronium. Clinicians are advised to be aware that clindamycin synergistically increases the degree of rocuronium-induced neuromuscular block, even when neostigmine is present.

Keyword

Clindamycin; Neostigmine; Neuromuscular block; Reversal; Rocuronium; Synergy

MeSH Terms

Androstanols
Animals
Clindamycin
Humans
Isotonic Solutions
Male
Muscle Relaxation
Neostigmine
Neuromuscular Blockade
Rats
Rats, Sprague-Dawley
Refractory Period, Electrophysiological
Androstanols
Clindamycin
Isotonic Solutions
Neostigmine