Betamethasone-induced resistance to neuromuscular blockade: a comparison of atracurium and vecuronium in vitro.
Steroids induce resistance to neuromuscular blocking drugs. Betamethasone-induced resistance to vecuronium has been demonstrated in vitro, and a presynaptic site of interaction has been suggested. This study investigated whether atracurium is similarly affected. Rat phrenic nerve-hemidiaphragm preparations were bathed in a physiologic solution, and one-half were exposed to betamethasone (1 mumol/L). Dose responses were recorded for atracurium (8-13 mumol/L) and vecuronium (2-12 mumol/L) for control and betamethasone-treated preparations. In comparison to control, the betamethasone groups had significantly less depression of muscle contraction force at all concentrations of atracurium (P = 0.0004) and vecuronium (P = 0.002). The calculated ED50 (50% depression of muscle contraction force, expressed as mean +/- SEM) for atracurium was 8.83 +/- 0.62 mumol/L for controls and 11.19 +/- 0.54 mumol/L for betamethasone-treated preparations. The calculated ED50 for vecuronium was 4.72 +/- 0.41 mumol/L for controls and 6.84 +/- 0.66 mumol/L for betamethasone-treated preparations. Betamethasone therefore increased the ED50 for atracurium by 27% and vecuronium by 45%; however, the magnitudes of these differences were not significant (P = 0.74) between the neuromuscular blocking agents. These results indicate that betamethasone-induced resistance to nondepolarizing neuromuscular blockade affects both atracurium and vecuronium to similar degrees in vitro.
Department of Community Health, Wellington School of Medicine, New Zealand.
B J
BJ
Robinson
E
E
Lee
D
D
Rees
G L
GL
Purdie
D C
DC
Galletly
D000818:Animals; D001279:Atracurium / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001623:Betamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects*; D051381:Rats; D014673:Vecuronium Bromide / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D001279:Atracurium; D014673:Vecuronium Bromide; D001623:Betamethasone