The online version of this article (doi:10.1186/cc10317) contains supplementary material, which is available to authorized users.
Armand Mekontso Dessap, Islem Ouanes contributed equally to this work.
The author(s) declare that they have no competing interests.
AMD participated in the conception and design of the study, helped to perform the statistical analysis, and drafted the manuscript. IO participated in collection of data, helped to perform the statistical analysis, and helped to draft the manuscript. NR and BB participated in collection of data and helped to draft the manuscript. CB and AH carried out atorvastatin pharmacokinetics and helped to draft the manuscript. SK helped to perform the statistical analysis and helped to draft the manuscript. CBB participated in the conception, design and coordination of the study, and helped to draft the manuscript. All authors read and approved the final manuscript.
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.
We 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.
Patients 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.
Continuing 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.
Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R, Cholesterol Treatment Trialists' (CTT) Collaborators: Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet 2005, 366: 1267-1278. PubMedCrossRef
Drug information/Product Labeling/Lipitor/Warning and precautions[ http://www.pdr.net/drugpages/productlabeling.aspx?mpcode=62402910#section-5.1]
Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM, Ramsay G, Zimmerma JL, Vincent JL, Levy MM: Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Intensive Care Med 2004, 30: 536-555. 10.1007/s00134-004-2210-z PubMedCrossRef
Vincent JL, de Mendonca A, Cantraine F, Moreno R, Takala J, Suter PM, Sprung CL, Colardyn F, Blecher S: Use of the SOFA score to assess the incidence of organ dysfunction/failure in intensive care units: results of a multicenter, prospective study. Working group on "sepsis-related problems" of the European Society of Intensive Care Medicine. Crit Care Med 1998, 26: 1793-1800. 10.1097/00003246-199811000-00016 PubMedCrossRef
Vincent JL, Moreno R, Takala J, Willatts S, De Mendonca A, Bruining H, Reinhart CK, Suter PM, Thijs LG: The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the Working Group on Sepsis-Related Problems of the European Society of Intensive Care Medicine. Intensive Care Med 1996, 22: 707-710. 10.1007/BF01709751 PubMedCrossRef
The R Foundation[ http://www.R-project.org]
McCabe WR, GG J: Gram-negative bacteremia. Etiology and ecology. Arch Intern Med 1963, 110: 847-855. CrossRef
- Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study
Armand Mekontso Dessap
- BioMed Central
Neu im Fachgebiet AINS
Meistgelesene Bücher aus dem Fachgebiet AINS
Mail Icon II