Differential effects of neuromuscular blockers on twitches and tetani in the isolated rat muscle: a multiple comparison study using simultaneous confidence intervals

• Published in: Fundamental & clinical pharmacology Vol. 22; no. 5; pp. 511 - 516
• Main Authors: Ching, L.H., Serra, C.S.M., Nascimento, D.C., De Oliveira, M.J., Oliveira, A.C.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.10.2008; Blackwell
• Subjects: Animals; Biological and medical sciences; Confidence Intervals; differential effects; Female; In Vitro Techniques; Male; Medical sciences; multiple comparisons; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Skeletal - drug effects; Muscle, Skeletal - physiology; neuromuscular blockers; Neuromuscular Blocking Agents - pharmacology; Neuromuscular Blocking Agents - therapeutic use; Neuromuscular Junction - drug effects; Neuromuscular Junction - physiology; Pharmacology. Drug treatments; Rats; Rats, Wistar; simultaneous confidence intervals; Spasm - physiopathology; Spasm - prevention & control; tetani; Tetany - physiopathology; Tetany - prevention & control; twitches; Rat; neuromuscular blockers; simultaneous confidence intervals; Rodentia; twitches; In vitro; tetani; Confidence interval; Neuromuscular blocking agent; differential effects; Vertebrata; Mammalia; Animal; Muscle; multiple comparisons; Comparative study
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/j.1472-8206.2008.00630.x

In the present work a comparative quantitative evaluation of the differential effects of neuromuscular blockers on twitches and tetani was performed, encompassing: atracurium, cisatracurium, mivacurium, pancuronium, rocuronium and vecuronium. The sciatic nerve‐extensor digitorum longus muscle of the rat was used, in vitro. Twitches were evoked at 0.1 Hz and tetani at 50 Hz. The differential effects of the studied compounds on twitches and tetani were statistically compared using simultaneous confidence intervals for the ratios between mean IC50 for the block of twitches and mean IC50 for the block of tetani. The results of ratios of mean IC50 together with their corresponding 95% simultaneous confidence intervals were: vecuronium: 2.5 (1.8–3.5); mivacurium: 3.8 (3.0–4.9); pancuronium: 3.9 (2.0–7.6); rocuronium: 6.1 (3.8–9.9); atracurium: 9.0 (6.4–12.6); cisatracurium: 13.1 (6.0–28.4). Using the criteria that neuromuscular blockers displaying disjunct confidence intervals for the ratios of mean IC50 differ statistically with regard to differential effects on twitches and tetani, significant differences in ratios of IC50 were detected in the following cases: vecuronium vs. rocuronium, vs. atracurium and vs. cisatracurium and mivacurium vs: cisatracurium and vs. atracurium. The results show that the magnitude of the differential effects of neuromuscular blockers on twitches and tetani, as evaluated in the present work in the form of ratios of mean IC50, does not depend on the chemical structure (comparing steroidal and isoquinolinic compounds), but seems to depend on differential pre‐ and post‐synaptic effects of the compounds. It is also suggested that the greater the ability of a compound to block twitches and tetani in a differential manner, the safer is the compound from the clinical anesthesiology viewpoint.