Clinical pharmacology of muscle relaxants in patients with burns

Pathophysiologic changes accompanying burn trauma can alter the pharmacokinetics and pharmacodynamic responses to neuromuscular relaxants. Pathophysiologic changes that can potentially affect kinetics in the hypermetabolic phase of burn injury include increased hepatic blood flow, increased glomerular filtration, and increased protein binding. Except for D-tubocurarine, the pharmacokinetics of neuromuscular relaxants relative to burn trauma have not been studied. The unbound volume of distribution, clearance, and half-life of D-tubocurarine were not significantly different from controls, but the plasma binding and renal elimination at 24 hours was increased in burn patients. The aberrant pharmacodynamic responses to neuromuscular relaxants in burn patients include the potential for lethal hyperkalemia with the administration of depolarizing relaxant, succinylcholine, and a 2.5- to 5.0-fold increase in the dose or plasma concentration requirement for nondepolarizing relaxant, including D-tubocurarine, metocurine, pancuronium, and atracurium. The altered pharmacodynamic responses are probably related to an increase in nicotinic acetylcholine receptor number. An alternative to succinylcholine to produce rapid-onset neuromuscular paralysis include the administration of 3XED95 doses of pancuronium and metocurine in combination (but recovery from paralysis is prolonged). Vecuronium and atracurium have good cardiovascular stability and faster recovery times even in high dosages in healthy patients, but the pharmacokinetics and pharmacodynamics of these drugs in patients with burns have not been fully characterized.
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				T. Han, H. Kim, J. Bae, K. Kim, and J. A. J. Martyn Neuromuscular Pharmacodynamics of Rocuronium in Patients with Major Burns Anesth. Analg., August 1, 2004; 99(2): 386 - 392. [Abstract] [Full Text] [PDF]