title: Statins do not prevent acute organ failure in ventilated ICU patients: single-centre retrospective cohort study.
abstract: BACKGROUND
  Observational studies suggest statin therapy reduces incident sepsis, but few studies have examined the impact on new organ failure. We tested the hypothesis that statin therapy, administered for standard clinical indications to ventilated intensive care unit patients, prevents acute organ failure without harming the liver.
  
  
  METHODS
  We performed a retrospective, single-centre cohort study in a tertiary mixed medical/surgical intensive care unit. Mechanically ventilated patients without nonrespiratory organ failure within 24 hours after admission were assessed (during the first 15 days) for new acute organ failure (defined as Sequential Organ Failure Assessment (SOFA) score 3 or 4), liver failure (defined as new hepatic SOFA ≥ 3, or a 1.5 times increase of bilirubin from baseline to a value ≥ 20 mmol/l), and alanine transferase (ALT) > 165 IU/l. The effect of statin administration was explored in generalised linear mixed models.
  
  
  RESULTS
  A total of 1,397 patients were included. Two hundred and nineteen patients received a median (interquartile range) of three (two, eight) statin doses. Patients receiving statins were older (67.4 vs. 55.5 years, P < 0.0001), less likely female (25.1% vs. 37.9%, P = 0.0003) and sicker (Acute Physiology and Chronic Health Evaluation (APACHE) II score 20.3 vs. 17.8, P < 0.0001). Considering outcome events at least 1 day after statin administration, statin patients were equally likely to develop acute organ failure (28.4% vs. 22.3%, P = 0.29) and hepatic failure (9.5% vs. 7.6%, P = 0.34), but were more likely to experience an ALT increase to > 165 IU/l ((11.2% vs. 4.8%, P = 0.0005). Multivariable analysis showed that APACHE II score (odds ratio (OR) = 1.05 per point; 95% confidence interval (CI) = 1.03 to 1.07) and APACHE II admission category (P < 0.0001), but not statin administration (OR = 1.21; 95% CI = 0.92 to 1.62), were significantly associated with acute organ failure occurring on or after the day of first statin administration. Statin administration was not associated with liver impairment (OR = 1.08; 95% CI = 0.66 to 1.77) but was associated with a rise in ALT > 165 IU/l (OR = 2.25; 95% CI = 1.32 to 3.84), along with APACHE II score (P = 0.016) and admission ALT (P = 0.0001).
  
  
  CONCLUSIONS
  Concurrent statin therapy does not appear to protect against the development of new acute organ failure in critically ill, ventilated patients. The lack of effect may be due to residual confounding, a relatively low number of doses received, or an absence of true effect. Randomised controlled trials are needed to confirm a protective effect.
authors.affiliation: Critical Care & Anaesthesia Research Group, King's College London, St Thomas' Hospital, Westminster Bridge Road, London SE1 7EH, UK. marius.terblanche@kcl.ac.uk
authors.forename: Marius J
authors.initials: MJ
authors.lastname: Terblanche
authors.forename: Ruxandra
authors.initials: R
authors.lastname: Pinto
authors.forename: Craig
authors.initials: C
authors.lastname: Whiteley
authors.forename: Stephen
authors.initials: S
authors.lastname: Brett
authors.forename: Richard
authors.initials: R
authors.lastname: Beale
authors.forename: Neill K J
authors.initials: NK
authors.lastname: Adhikari
mesh_terms: D000328:Adult; D000368:Aged; D003422:Critical Care / Q000379:methods*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007362:Intensive Care Units; D016014:Linear Models; D008107:Liver Diseases / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000517:prevention & control*; D012121:Respiration, Artificial; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors