Partial Neuromuscular Blockade during Partial Ventilatory Support in Sedated Patients with High Tidal Volumes

Abstract

RATIONALE: Controlled mechanical ventilation is used to deliver lung-protective ventilation in patients with acute respiratory distress syndrome. Despite recognized benefits, such as preserved diaphragm activity, partial support ventilation modes may be incompatible with lung-protective ventilation due to high Vt and high transpulmonary pressure. As an alternative to high-dose sedatives and controlled mechanical ventilation, pharmacologically induced neuromechanical uncoupling of the diaphragm should facilitate lung-protective ventilation under partial support modes. OBJECTIVES: To investigate whether partial neuromuscular blockade can facilitate lung-protective ventilation while maintaining diaphragm activity under partial ventilatory support. METHODS: In a proof-of-concept study, we enrolled 10 patients with lung injury and a Vt greater than 8 ml/kg under pressure support ventilation (PSV) and under sedation. After baseline measurements, rocuronium administration was titrated to a target Vt of 6 ml/kg during neurally adjusted ventilatory assist (NAVA). Thereafter, patients were ventilated in PSV and NAVA under continuous rocuronium infusion for 2 hours. Respiratory parameters, hemodynamic parameters, and blood gas values were measured. MEASUREMENTS AND MAIN RESULTS: Rocuronium titration resulted in significant declines of Vt (mean +/- SEM, 9.3 +/- 0.6 to 5.6 +/- 0.2 ml/kg; P < 0.0001), transpulmonary pressure (26.7 +/- 2.5 to 10.7 +/- 1.2 cm H2O; P < 0.0001), and diaphragm electrical activity (17.4 +/- 2.3 to 4.5 +/- 0.7 muV; P < 0.0001), and could be maintained under continuous rocuronium infusion. During titration, pH decreased (7.42 +/- 0.02 to 7.35 +/- 0.02; P < 0.0001), and mean arterial blood pressure increased (84 +/- 6 to 99 +/- 6 mm Hg; P = 0.0004), as did heart rate (83 +/- 7 to 93 +/- 8 beats/min; P = 0.0004). CONCLUSIONS: Partial neuromuscular blockade facilitates lung-protective ventilation during partial ventilatory support, while maintaining diaphragm activity, in sedated patients with lung injury.