Abstract
IntroductionObservational 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.MethodsWe 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.ResultsA 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).ConclusionsConcurrent 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.
Highlights
Observational studies suggest statin therapy reduces incident sepsis, but few studies have examined the impact on new organ failure
Many patients suffering from severe infections and early sepsis - conditions associated with deterioration and the development of acute organ failure - require mechanical ventilation after intensive care unit (ICU) admission [1,2,3]
Our objectives were to determine whether statin therapy, as administered by clinicians to a cohort of mechanically ventilated patients without nonrespiratory organ failure within 24 hours of ICU admission, (1) reduces the incidence of a composite endpoint of new nonrespiratory organ failure or the worsening of existing respiratory dysfunction during the first 15 days of admission, and (2) is associated with liver impairment as determined by changes in bilirubin and alanine transferase (ALT)
Summary
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. While numerous observational studies support the notion of improved sepsis-related outcome in those patients receiving long-term statin therapy, it is not known whether such therapy protects critically ill patients against the development of new acute organ failure or the worsening of existing organ dysfunction [11,12]. Our objectives were to determine whether statin therapy, as administered by clinicians to a cohort of mechanically ventilated patients without nonrespiratory organ failure within 24 hours of ICU admission, (1) reduces the incidence of a composite endpoint of new nonrespiratory organ failure or the worsening of existing respiratory dysfunction during the first 15 days of admission, and (2) is associated with liver impairment as determined by changes in bilirubin and alanine transferase (ALT). We hypothesised that statin therapy does not worsen liver function in this high-risk, clinically important population and protects them against new acute organ failure
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