G.P.2.06 Diaphragm muscle weakness in an experimental intensive care unit model

Abstract

Diaphragm muscle dysfunction contributing to weaning failure in critically ill patients remains unclear. It may not fully depend on ventilator-induced modifications. Sepsis and administration of pharmacological agents such as corticosteroids and neuromuscular blocking agents may be involved. The objectives of this study were to examine to which extent sepsis, corticosteroid treatment and neuromuscular blocking agent administration aggravate ventilator-related diaphragm dysfunction using a unique piglet intensive care unit model. Piglets were randomly sham-operated, or for five days, mechanically ventilated, mechanically ventilated together with an endotoxin-induced sepsis, mechanically ventilated together with corticosteroid treatment, mechanically ventilated together with neuromuscular blocking agent administration, or mechanically ventilated together with sepsis, corticosteroid and neuromuscular blocking agent. On day 5, muscle fibers were isolated from diaphragm biopsies and frozen or membrane-permeabilized. The cross-sectional area and maximal force normalized to cross-sectional area were evaluated at the single muscle fiber level. Myosin heavy chain and actin protein mRNA expression were assessed in diaphragm muscle samples. Results show (i) a decrease in fiber maximal force normalized to cross-sectional area coupled with a reduction in myosin heavy chain mRNA level in all mechanically ventilated piglets; (ii) a decrease in fiber size in piglets that were mechanically ventilated in combination with sepsis, corticosteroid and neuromuscular blocking agent. In conclusion, five days mechanical ventilation had a significant negative effect on the force generating capacity of individual diaphragm muscle fibers. Sepsis, corticosteroid or neuromuscular blocking agent had no additional on force generation or muscle size, but both force normalized to fiber cross-sectional area and fiber size decreased significantly when all were combined with mechanical ventilation.