Deep sedation and mechanical ventilation without paralysis for 3 weeks in normal beagles - Exaggerated resistance to metocurine in gastrocnemius muscle

Background: Patients in the intensive care unit may have muscle weakness in the recovery phase, and disuse atrophy may play a role in this weakness. T o assess this problem, the authors measured changes in the potency of the n ondepolarizing neuromuscular blocking agent metocurine in a canine model th at involved 3 weeks of intensive care, nonparalyzing anesthesia with pentob arbital and positive-pressure ventilation. Methods: Six dogs were anesthetized with pentobarbital to a sufficient dept h that spontaneous and reflex muscle movements were absent. Their tracheas were intubated, their lungs were mechanically ventilated, and they received round-the-clock intensive medical and nursing care for 3 weeks, Transduced gastrocnemius muscle responses to metocurine were determined weekly. A 4- to 15-min infusion of 148-4,300 mu g/min (longer durations and greater conc entrations on progressive weeks) yielded more than 80% paralysis. Serial me tocurine plasma concentrations during the onset of the block and recovery p rovided data to determine pharmacokinetics using NON-MEM. Metocurine plasma concentrations and the degree of paralysis were used to model the effect c ompartment equilibration constant, and the Hill equation was used to yield the slope factor and potency within the effect compartment, Results: The metocurine effect compartment concentration associated with a 50% diminution of twitch height after 3 weeks was 1,716 +/- 1,208 ng/ml (me an +/- SD), which was significantly different from 257 +/- 34 ng/ml, the va lue on day 0, There were no pharmacokinetic differences. Conclusion: The absence of muscle tone and reflex responsiveness for 3 week s was associated with exaggerated resistance to the neuromuscular blocker m etocurine.