Effects of prolonged mechanical ventilation and inactivity on piglet diaphragm function

Objectives: Muscle weakness is associated with immobilization, prolonged mechanical ventilation, critical illness and various critical care therapies. This study used an animal model simulating the critical care environment to investigate the effects of 5 days' mechanical ventilation and inactivity on diaphragm contractility and neurophysiologic function. Design: Prospective laboratory study. Setting: Animal research laboratory. Subjects: Seven 2-3 month old piglets weighing 20-25 kg. Interventions: The animals received constant-flow, volume-controlled mechanical ventilation (Tv 12-15 ml/kg, PEEP 3-5 cmH(2)O, I:E 1:2) and sedation without paralysis, and spontaneous breathing efforts were prevented. Evoked diaphragm contractions were achieved by transvenous phrenic nerve pacing. Measurements and main findings: Transdiaphragmatic pressure (Pdi) measurements were used to assess force frequency relationships. Evoked electrophysiologic measures included lowest stimulus threshold and latency, compound muscle action potential (CMAP) amplitude and duration, and amplitude during repetitive nerve stimulation at 3 Hz. Lung function measures included airway pressures, tidal and minute volumes, and dynamic compliance and resistance. There were no clinically significant changes in hemodynamics, oxygenation or ventilation. Indirect measures of lung volume remained stable. Pdi decreased by 20% at all frequencies tested and was accompanied by a 30% decrease in evoked CMAP amplitude, (6.7 +/- 4.7 mV to 4.5 +/- 3.9 mV, p=0.01) while CMAP threshold, latency and duration were unchanged and no significant decrement in amplitude was seen during repetitive stimulation at 3 Hz. Conclusion: In this in-vivo model of prolonged mechanical ventilation in an intensive caring setting, 5 days of mechanical ventilation with sedation and complete diaphragm inactivity resulted in disturbed diaphragm contractility and activation, while nerve conduction and neuromuscular transmission were not affected. Based on these findings, it is likely that the changes seen occur at the level of peripheral muscle.