title: Partial Neuromuscular Blockade during Partial Ventilatory Support in Sedated Patients with High Tidal Volumes.
abstract: 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.
  
  
  
  To investigate whether partial neuromuscular blockade can facilitate lung-protective ventilation while maintaining diaphragm activity under partial ventilatory support.
  
  
  
  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.
  
  
  
  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 μV; 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).
  
  
  
  Partial neuromuscular blockade facilitates lung-protective ventilation during partial ventilatory support, while maintaining diaphragm activity, in sedated patients with lung injury.
authors.affiliation: 1 Department of Critical Care Medicine and.
authors.forename: Jonne
authors.initials: J
authors.lastname: Doorduin
authors.affiliation: 1 Department of Critical Care Medicine and.
authors.forename: Joeke L
authors.initials: JL
authors.lastname: Nollet
authors.affiliation: 1 Department of Critical Care Medicine and.
authors.forename: Lisanne H
authors.initials: LH
authors.lastname: Roesthuis
authors.affiliation: 2 Department of Pulmonary Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Hieronymus W H
authors.initials: HW
authors.lastname: van Hees
authors.affiliation: 3 Department of Critical Care Medicine, St. Michael's Hospital, Toronto, Ontario, Canada; and.|4 Keenan Research Centre for Biomedical Science, Toronto, Ontario, Canada.
authors.forename: Laurent J
authors.initials: LJ
authors.lastname: Brochard
authors.affiliation: 3 Department of Critical Care Medicine, St. Michael's Hospital, Toronto, Ontario, Canada; and.|4 Keenan Research Centre for Biomedical Science, Toronto, Ontario, Canada.
authors.forename: Christer A
authors.initials: CA
authors.lastname: Sinderby
authors.affiliation: 1 Department of Critical Care Medicine and.
authors.forename: Johannes G
authors.initials: JG
authors.lastname: van der Hoeven
authors.affiliation: 1 Department of Critical Care Medicine and.
authors.forename: Leo M A
authors.initials: LM
authors.lastname: Heunks
mesh_terms: D000328:Adult; D000368:Aged; D000732:Androstanols / Q000494:pharmacology*; D003964:Diaphragm / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019148:Neuromuscular Blockade / Q000379:methods*; D003473:Neuromuscular Nondepolarizing Agents / Q000494:pharmacology; D012121:Respiration, Artificial / Q000379:methods*; D012128:Respiratory Distress Syndrome / Q000503:physiopathology*; D000077123:Rocuronium; D013990:Tidal Volume / Q000502:physiology
chemical_list: D000732:Androstanols; D003473:Neuromuscular Nondepolarizing Agents; D000077123:Rocuronium
keywords: acute respiratory distress syndrome; diaphragm; lung-protective ventilation; neuromuscular blocking agents; partial support ventilation