title: Effect of driving pressure on mortality in ARDS patients during lung protective mechanical ventilation in two randomized controlled trials.
abstract: Driving pressure (ΔPrs) across the respiratory system is suggested as the strongest predictor of hospital mortality in patients with acute respiratory distress syndrome (ARDS). We wonder whether this result is related to the range of tidal volume (VT). Therefore, we investigated ΔPrs in two trials in which strict lung-protective mechanical ventilation was applied in ARDS. Our working hypothesis was that ΔPrs is a risk factor for mortality just like compliance (Crs) or plateau pressure (Pplat,rs) of the respiratory system.
  
  
  
  We performed secondary analysis of data from 787 ARDS patients enrolled in two independent randomized controlled trials evaluating distinct adjunctive techniques while they were ventilated as in the low VTarm of the ARDSnet trial. For this study, we used VT, positive end-expiratory pressure (PEEP), Pplat,rs, Crs, ΔPrs, and respiratory rate recorded 24 hours after randomization, and compared them between survivors and nonsurvivors at day 90. Patients were followed for 90 days after inclusion. Cox proportional hazard modeling was used for mortality at day 90. If colinearity between ΔPrs, Crs, and Pplat,rs was verified, specific Cox models were used for each of them.
  
  
  
  Both trials enrolled 805 patients of whom 787 had day-1 data available, and 533 of these survived. In the univariate analysis, ΔPrs averaged 13.7 ± 3.7 and 12.8 ± 3.7 cmH2O (P = 0.002) in nonsurvivors and survivors, respectively. Colinearity between ΔPrs, Crs and Pplat,rs, which was expected as these variables are mathematically coupled, was statistically significant. Hazard ratios from the Cox models for day-90 mortality were 1.05 (1.02-1.08) (P = 0.005), 1.05 (1.01-1.08) (P = 0.008) and 0.985 (0.972-0.985) (P = 0.029) for ΔPrs, Pplat,rs and Crs, respectively. PEEP and VTwere not associated with death in any model.
  
  
  
  When ventilating patients with low VT, ΔPrs is a risk factor for death in ARDS patients, as is Pplat,rs or Crs. As our data originated from trials from which most ARDS patients were excluded due to strict inclusion and exclusion criteria, these findings must be validated in independent observational studies in patients ventilated with a lung protective strategy.
  
  
  
  Clinicaltrials.gov NCT00299650 . Registered 6 March 2006 for the Acurasys trial. Clinicaltrials.gov NCT00527813 . Registered 10 September 2007 for the Proseva trial.
authors.affiliation: Réanimation Médicale Groupement Hospitalier Nord Hospices civils de Lyon, Lyon, France. claude.guerin@chu-lyon.fr.|Université de Lyon, 1 69100, Villeurbanne, France. claude.guerin@chu-lyon.fr.|Institut Mondor de Recherche Biomédicale, INSERM 955 Equipe 13, Créteil, France. claude.guerin@chu-lyon.fr.
authors.forename: Claude
authors.initials: C
authors.lastname: Guérin
authors.affiliation: Hôpitaux de Marseille Hôpital Nord Réanimation des Détresses Respiratoires et des Infections Sévères, Marseille, 13015, France.|Aix-Marseille University EA 3279 Research Unit Department of Public Health Medecine School University Marseille, Marseille, France.|URMITE UMR CNRS 7278, Marseille, 13005, France.
authors.forename: Laurent
authors.initials: L
authors.lastname: Papazian
authors.affiliation: Réanimation Médicale CHU de Nantes, Nantes, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Reignier
authors.affiliation: Centre de Coordination et de Lutte Contre les Infections Nosocomiales Sud-Est, Saint-Genis Laval, France.
authors.forename: Louis
authors.initials: L
authors.lastname: Ayzac
authors.affiliation: Aix-Marseille University EA 3279 Research Unit Department of Public Health Medecine School University Marseille, Marseille, France.
authors.forename: Anderson
authors.initials: A
authors.lastname: Loundou
authors.affiliation: Hôpitaux de Marseille Department of Research and Innovation Support Unit for clinical research and economic evaluation, Marseille, 13005, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Forel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D017052:Hospital Mortality / Q000639:trends*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011175:Positive-Pressure Respiration / Q000009:adverse effects / Q000379:methods*; D012121:Respiration, Artificial / Q000009:adverse effects / Q000379:methods; D012128:Respiratory Distress Syndrome / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy*; D013990:Tidal Volume / Q000502:physiology*
keywords: ARDS; Compliance; Driving pressure; Lung protective ventilation; Neuromuscular blocking agents; Plateau pressure; Prone position