title: Impact of statin therapy on mortality in patients with sepsis-associated acute respiratory distress syndrome (ARDS) depends on ARDS severity: a prospective observational cohort study.
abstract: BACKGROUND
  Previous investigations have presumed a potential therapeutic effect of statin therapy in patients with acute respiratory distress syndrome (ARDS). Statins are expected to attenuate inflammation in the lungs of patients with ARDS due to their anti-inflammatory effects. Clinical investigations of the role of statin therapy have revealed contradictory results. This study aimed to investigate whether pretreatment and continuous therapy with statins in patients with sepsis-associated ARDS are associated with 28-day survival according to disease severity (mild, moderate, or severe).
  
  
  METHODS
  Patients with sepsis-associated ARDS from the surgical intensive care were enrolled in this prospective observational investigation. ARDS was classified into three groups (mild, moderate, and severe); 28-day mortality was recorded as the primary outcome variable and organ failure was recorded as secondary outcome variable. Sequential Organ Failure Assessment scores and the requirements for organ support were evaluated throughout the observational period to assess organ failure.
  
  
  RESULTS
  404 patients with sepsis-associated ARDS were enrolled in this investigation. The distribution of the ARDS subgroups was 13 %, 59 %, and 28 % for mild, moderate, and severe disease, respectively. Statin therapy improved 28-day survival exclusively in the patients with severe ARDS compared with patients without statin therapy (88.5 % and 62.5 %, respectively; P = 0.0193). To exclude the effects of several confounders, we performed multivariate Cox regression analysis, which showed that statin therapy remained a significant covariate for mortality (hazard ratio, 5.46; 95 % CI, 1.38-21.70; P = 0.0156). Moreover, after carrying a propensity score-matching in the severe ARDS cohort, Kaplan-Meier survival analysis confirmed the improved 28-day survival among patients with statin therapy (P = 0.0205). Patients with severe ARDS who received statin therapy had significantly more vasopressor-free days compared with those without statin therapy (13 ± 7 and 9 ± 7, respectively; P = 0.0034), and they also required less extracorporeal membrane oxygenation (ECMO) therapy and had more ECMO-free days (18 ± 9 and 15 ± 9, respectively; P = 0.0873).
  
  
  CONCLUSIONS
  This investigation suggests a beneficial effect of continuous statin therapy in patients with severe sepsis-associated ARDS and a history of prior statin therapy. Further study is warranted to elucidate this potential effect.
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, D-37075, Goettingen, Germany. ashham.mansur@med.uni-goettingen.de.
authors.forename: Ashham
authors.initials: A
authors.lastname: Mansur
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, D-37075, Goettingen, Germany. m.steinau@gmx.de.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Steinau
authors.affiliation: Department of Cardiothoracic Transplantation & Mechanical Support, Royal Brompton and Harefield Hospital, Harefield, Hill End Road, UB9 6JH, London, UK. a.popov@rbht.nhs.uk.
authors.forename: Aron Frederik
authors.initials: AF
authors.lastname: Popov
authors.affiliation: Department of General and Visceral Surgery, University Medical Center, Georg August University, D-37075, Goettingen, Germany. mghadim@uni-goettingen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Ghadimi
authors.affiliation: Department of Medical Statistics, University Medical Center, Georg August University, D-37075, Goettingen, Germany. tim.beissbarth@ams.med.uni-goettingen.de.
authors.forename: Tim
authors.initials: T
authors.lastname: Beissbarth
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, D-37075, Goettingen, Germany. martin.bauer@med.uni-goettingen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Bauer
authors.affiliation: Department of Anesthesiology, University Medical Center, Georg August University, D-37075, Goettingen, Germany. jhinz@med.uni-goettingen.de.
authors.forename: José
authors.initials: J
authors.lastname: Hinz
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D057216:Propensity Score; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000401:mortality* / Q000503:physiopathology; D018805:Sepsis / Q000150:complications
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors