Abstract
IntroductionRecent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question.MethodsWe retrospectively compared patients with severe sepsis and septic shock in whom statin therapy had been discontinued or continued. The primary endpoint was the number of organ failure-free days at day 14. Secondary end-points included hospital mortality and safety. The association of statin continuation with outcome was evaluated for crude analysis and after propensity score matching and adjustment. We also measured plasma atorvastatin concentrations in a separate set of ICU septic patients continuing the drug.ResultsPatients in whom statin therapy had been continued in the ICU (n = 44) had significantly more organ failure-free days (11 [6-14] vs. 6 [0-12], mean difference of 2.34, 95%CI from 0.47 to 5.21, P = 0.03) as compared to others (n = 32). However, there were important imbalances between groups, with more hospital-acquired infections, more need for surgery before ICU admission, and a trend towards more septic shock at ICU admission in the discontinuation group. The significant association of statin continuation with organ failure free days found in the crude analysis did not persist after propensity-matching or multivariable adjustment: beta coefficients [95% CI] of 2.37 [-0.96 to 5.70] (P = 0.20) and 2.24 [-0.43 to 4.91] (P = 0.11) respectively. We found particularly high pre-dose and post-dose atorvastatin concentrations in ICU septic patients continuing the drug.ConclusionsContinuing statin therapy in ICU septic patients was not associated with reduction in the severity of organ failure after matching and adjustment. In addition, the very high plasma concentrations achieved during continuation of statin treatment advocates some caution.
Highlights
Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis
Patients During the study-period, 81 patients receiving chronic statin therapy were hospitalized for severe sepsis or septic shock in our intensive care unit (ICU)
Our study suggests that the lesser morbidity associated with continuation of ongoing statin therapy in patients with severe sepsis or septic shock may be influenced by confounders
Summary
Recent publications suggest potential benefits from statins as a preventive or adjuvant therapy in sepsis. Whether ongoing statin therapy should be continued or discontinued in patients admitted in the intensive care unit (ICU) for sepsis is open to question. Many experimental models have shown pleiotropic activity of statins The aim of this preliminary report was: to evaluate the effectiveness and safety of statin therapy continuation on the incidence of organ failure in septic patients (compared with patients in whom statins were routinely stopped); and to assess atorvastatin plasma concentrations during its continuation in a subset of ICU septic patients
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