title: A randomised controlled trial of an open lung strategy with staircase recruitment, titrated PEEP and targeted low airway pressures in patients with acute respiratory distress syndrome.
abstract: BACKGROUND
  Tidal volume and plateau pressure minimisation are the standard components of a protective lung ventilation strategy for patients with acute respiratory distress syndrome (ARDS). Open lung strategies, including higher positive end-expiratory pressure (PEEP) and recruitment manoeuvres to date have not proven efficacious. This study examines the effectiveness and safety of a novel open lung strategy, which includes permissive hypercapnia, staircase recruitment manoeuvres (SRM) and low airway pressure with PEEP titration.
  
  
  METHODS
  Twenty ARDS patients were randomised to treatment or ARDSnet control ventilation strategies. The treatment group received SRM with decremental PEEP titration and targeted plateau pressure < 30 cm H2O. Gas exchange and lung compliance were measured daily for 7 days and plasma cytokines in the first 24 hours and on days 1, 3, 5 and 7 (mean ± SE). Duration of ventilation, ICU stay and hospital stay (median and interquartile range) and hospital survival were determined.
  
  
  RESULTS
  There were significant overall differences between groups when considering plasma IL-8 and TNF-α. For plasma IL-8, the control group was 41% higher than the treatment group over the seven-day period (ratio 1.41 (1.11 to 1.79), P = 0.01), while for TNF-α the control group was 20% higher over the seven-day period (ratio 1.20 (1.01 to 1.42) P = 0.05). PaO2/FIO2 (204 ± 9 versus 165 ± 9 mmHg, P = 0.005) and static lung compliance (49.1 ± 2.9 versus 33.7 ± 2.7 mls/cm H2O, P < 0.001) were higher in the treatment group than the control group over seven days. There was no difference in duration of ventilation (180 (87 to 298) versus 341 (131 to 351) hrs, P = 0.13), duration of ICU stay (9.9 (5.6 to 14.8) versus 16.0 (8.1 to 19.3) days, P = 0.19) and duration of hospital stay (17.9 (13.7 to 34.5) versus 24.7 (20.5 to 39.8) days, P = 0.16) between the treatment and control groups.
  
  
  CONCLUSIONS
  This open lung strategy was associated with greater amelioration in some systemic cytokines, improved oxygenation and lung compliance over seven days. A larger trial powered to examine clinically-meaningful outcomes is warranted.
  
  
  BACKGROUND
  ACTRN12607000465459.
authors.affiliation: Intensive Care Unit, The Alfred, Commercial Road, Melbourne, VIC 3181, Australia. carol.hodgson@monash.edu
authors.forename: Carol L
authors.initials: CL
authors.lastname: Hodgson
authors.forename: David V
authors.initials: DV
authors.lastname: Tuxen
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Davies
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bailey
authors.forename: Alisa M
authors.initials: AM
authors.lastname: Higgins
authors.forename: Anne E
authors.initials: AE
authors.lastname: Holland
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Keating
authors.forename: David V
authors.initials: DV
authors.lastname: Pilcher
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Westbrook
authors.forename: David J
authors.initials: DJ
authors.lastname: Cooper
authors.forename: Alistair D
authors.initials: AD
authors.lastname: Nichol
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D006935:Hypercapnia; D016209:Interleukin-8 / Q000097:blood; D008170:Lung Compliance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D010100:Oxygen / Q000097:blood; D010865:Pilot Projects; D011175:Positive-Pressure Respiration / Q000379:methods*; D011312:Pressure; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D013990:Tidal Volume; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D010100:Oxygen