Resistance to atracurium in thermally injured rats: the roles of time, activity, and pharmacodynamics

Thermal injury induces resistance to nondepolarizing muscle relaxants in patients. Because the mechanism of the resistance is unknown, the authors have sought to establish thermally injured rats as a suitable model for subsequent detailed studies of mechanisms. Two hundred twenty-five- to 250-g rats...

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Bibliographic Details
Published in:Anesthesiology (Philadelphia) 1988-11, Vol.69 (5), p.696-701
Main Authors: PAVLIN, E. G, HASCHKE, R. H, MARATHE, P, SLATTERY, J. T, HOWARD, M. L, BUTLER, S. H
Format: Article
Language:English
Subjects:
Anesthetics. Neuromuscular blocking agents
Animals
Atracurium - pharmacology
Biological and medical sciences
Burns - physiopathology
Female
Medical sciences
Motor Activity
Muscle Contraction - drug effects
Muscle Relaxation - drug effects
Neuropharmacology
Pharmacology. Drug treatments
Rats
Rats, Inbred Strains
Time Factors
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Summary:Thermal injury induces resistance to nondepolarizing muscle relaxants in patients. Because the mechanism of the resistance is unknown, the authors have sought to establish thermally injured rats as a suitable model for subsequent detailed studies of mechanisms. Two hundred twenty-five- to 250-g rats sustained a 30% total body surface area thermal injury while anesthetized with pentobarbital. Another group had sham injury. Animal activity was monitored both by periods of direct observation and by use of activity cages. At 10, 20, 30, 40, 60, and 90 days after injury, rats were anesthetized and ventilated and the strength of contraction of their gastrocnemius produced by supramaximal stimulation of the sciatic nerve was measured before and after a bolus of atracurium (2.0 mg/kg) was administered. The plasma concentration required to diminish contraction to 50% of the preceding value (Cp50) was determined by atracurium infusion. Animals displayed the greatest resistance to atracurium at 40 days. The Cp50 value was also greatest at this time. The protein binding of atracurium was identical for both sham and injured groups. Activity for thermally injured resistant rats and for sham animals was not different. It appears that pharmacodynamic mechanisms are involved, and inactivity and disuse atrophy are not necessary in rats for development of resistance to nondepolarizing muscle relaxants after thermal injury.
ISSN:0003-3022
1528-1175
DOI:10.1097/00000542-198811000-00010