Deep sedation and mechanical ventilation without paralysis for 3 weeks in normal beagles

Exaggerated resistance to metocurine in gastrocnemius muscle

Gerald A. Gronert, Dennis L. Fung, Steve C. Haskins, Eugene Steffey

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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. To assess this problem, the authors measured changes in the potency of the nondepolarizing neuromuscular blocking agent metocurine in a canine model that involved 3 weeks of intensive care, nonparalyzing anesthesia with pentobarbital, and positive-pressure ventilation. Methods: Six dogs were anesthetized with pentobarbital to a sufficient depth 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 μg/min (longer durations and greater concentrations on progressive weeks) yielded more than 80% paralysis. Serial metocurine plasma concentrations during the onset of the block and recovery provided data to determine pharmacokinetics using NON-MEM. Metocurine plasma concentrations and the degree of paralysis were used to model the effect compartment 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 (mean ± SD), which was significantly different from 257 ± 34 ng/ml, the value on day 0. There were no pharmacokinetic differences. Conclusion: The absence of muscle tone and reflex responsiveness for 3 weeks was associated with exaggerated resistance to the neuromuscular blocker metocurine.

Original languageEnglish (US)
Pages (from-to)1741-1745
Number of pages5
JournalAnesthesiology
Volume90
Issue number6
DOIs
StatePublished - Jun 1 1999
Externally publishedYes

Fingerprint

Deep Sedation
Artificial Respiration
Paralysis
Skeletal Muscle
Neuromuscular Blocking Agents
Pentobarbital
Reflex
Pharmacokinetics
Atrophic Muscular Disorders
Critical Care Nursing
Muscles
Positive-Pressure Respiration
Muscle Weakness
Critical Care
Trachea
Intensive Care Units
metocurine
Canidae
Anesthesia
Dogs

Keywords

  • Disuse atrophy
  • Intensive care unit
  • Pharmacodynamics
  • Pharmacokinetics
  • Skeletal muscle neuromuscular blocking agents

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

Cite this

Deep sedation and mechanical ventilation without paralysis for 3 weeks in normal beagles : Exaggerated resistance to metocurine in gastrocnemius muscle. / Gronert, Gerald A.; Fung, Dennis L.; Haskins, Steve C.; Steffey, Eugene.

In: Anesthesiology, Vol. 90, No. 6, 01.06.1999, p. 1741-1745.

Research output: Contribution to journalArticle

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abstract = "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. To assess this problem, the authors measured changes in the potency of the nondepolarizing neuromuscular blocking agent metocurine in a canine model that involved 3 weeks of intensive care, nonparalyzing anesthesia with pentobarbital, and positive-pressure ventilation. Methods: Six dogs were anesthetized with pentobarbital to a sufficient depth 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 μg/min (longer durations and greater concentrations on progressive weeks) yielded more than 80{\%} paralysis. Serial metocurine plasma concentrations during the onset of the block and recovery provided data to determine pharmacokinetics using NON-MEM. Metocurine plasma concentrations and the degree of paralysis were used to model the effect compartment 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 (mean ± SD), which was significantly different from 257 ± 34 ng/ml, the value on day 0. There were no pharmacokinetic differences. Conclusion: The absence of muscle tone and reflex responsiveness for 3 weeks was associated with exaggerated resistance to the neuromuscular blocker metocurine.",
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