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

BackgroundPrevious 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).MethodsPatients 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.Results404 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).ConclusionsThis 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-015-0368-6) contains supplementary material, which is available to authorized users.

Pulmonary Infections in the Elderly Lead to Impaired Neutrophil Targeting, Which Is Improved by Simvastatin

“…Neutrophil migration could be rescued in vitro by simvastatin during LRTI and CAP, but not during a severe septic event and not in young donors. This might support the use of high-dose simvastatin preemptively or early during an infective insult in the elderly, but it suggests that a lack of efficacy would be seen in patients with established severe sepsis, corroborating data from interventional trials (12). In vitro chemotaxis findings were replicated for fMLP in the interventional trial in OH adults without impeding other vital neutrophil functions, such as phagocytosis and NET release.…”

“…3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) lower cholesterol, but some population studies and clinical trials have suggested survival benefits during infection (12). Predosing with statins improves outcomes in murine models of sepsis (13).…”

Statins for the prevention and treatment of acute lung injury and acute respiratory distress syndrome: A systematic review and meta‐analysis

“…Major characteristics of the included studies are summarized in Table . In general, the 13 studies, including four RCTs and nine cohort studies, were published between 2007 and 2015 covering a total of 12 145 patients.…”

Latent class analysis of ARDS subphenotypes: a secondary analysis of the statins for acutely injured lungs from sepsis (SAILS) study

“…In a prospective observational study, Mansur and colleagues found that the protection afforded by statin therapy in ARDS was only observed in those patients with severe ARDS. [34] In addition to lower ARDS severity, the SAILS trial also had a relatively low mortality rate amongst patients with severe ARDS at baseline (23.7%). Surprisingly, in the SAILS trial, 60-day mortality was highest in the mild ARDS population (44/145, 30.3%).…”