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Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study.

ABSTRACT: 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 67891011121314 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.

SUBMITTER: Mekontso Dessap A

PROVIDER: S-EPMC3387613 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study.

Mekontso Dessap Armand A Ouanes Islem I Rana Nerlep N Borghi Beatrice B Bazin Christophe C Katsahian Sandrine S Hulin Anne A Brun-Buisson Christian C

Critical care (London, England) 20110718 4

<h4>Introduction</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 21767409

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Project description:The role of recombinant activated protein C (aPC) during sepsis is still controversial. It showed anti-inflammatory effect and improved the microvascular perfusion in experimental models of septic shock. The present study was aimed at testing the hypothesis that recombinant aPC therapy improves the microcirculation during severe sepsis.Prospective observational study on patients admitted in a 12-beds intensive care unit of a university hospital from July 2010 to December 2011, with severe sepsis and at least two sepsis-induced organ failures occurring within 48 hours from the onset of sepsis, who received an infusion of aPC (24 mcg/kg/h for 96 hours) (aPC group). Patients with contraindications to aPC administration were also monitored (no-aPC group).At baseline (before starting aPC infusion, T0), after 24 hours (T1a), 48 hours (T1b), 72 hours (T1c) and 6 hours after the end of aPC infusion (T2), general clinical and hemodynamic parameters were collected and the sublingual microcirculation was evaluated with sidestream dark-field imaging. Total vessel density (TVD), perfused vessel density (PVD), De Backer score, microvascular flow index (MFIs), the proportion of perfused vessels (PPV) and the flow heterogeneity index (HI) were calculated for small vessels. The perfused boundary region (PBR) was measured as an index of glycocalyx damage. Variables were compared between time points and groups using non parametric or parametric statistical tests, as appropriate.In the 13 aPC patients mean arterial pressure (MAP), base excess, lactate, PaO2/FiO2 and the Sequential Organ Failure Assessment (SOFA) score significantly improved over time, while CI and ITBVI did not change. MFIs, TVD, PVD, PPV significantly increased over time and the HI decreased (p?<?0.05 in all cases), while the PBR did not change. No-aPC patients (n?=?9) did not show any change in the microcirculation over time. A positive correlation was found between MFIs and MAP. TVD, PVD and De Backer score negatively correlated with norepinephrine dose, and the SOFA score negatively correlated with MFIs, TVD and PVD.aPC significantly improves the microcirculation in patients with severe sepsis/septic shock.NCT01806428.

Project description:BackgroundThe use of ≥30 mL/Kg fluid bolus in congestive heart failure (CHF) patients presenting with severe sepsis or septic shock remained controversial due to the paucity of data.MethodsThe retrospective case-control study included 671 adult patients who presented to the emergency department of a tertiary care hospital from January 01, 2017 to December 31, 2019 with severe sepsis or septic shock. Patients were categorized into the CHF group and the non-CHF group. The primary outcome was to evaluate the compliance with ≥30 mL/Kg fluid bolus within 6 hours of presentation. The comparison of baseline characteristics and secondary outcomes were done between the groups who received ≥30 mL/Kg fluid bolus. For the subgroup analysis of the CHF group, it was divided based on if they received ≥30 mL/Kg fluid bolus or not, and comparison was done for baseline characteristics and secondary outcomes. Univariate and multivariable analyses were performed to explore the differences between the groups for in-hospital mortality and mechanical ventilation.ResultsThe use of ≥30 mL/Kg fluid bolus was low in both the CHF and non-CHF groups [39% vs. 66% (p<0.05)]. Mortality was higher in the CHF group [33% vs 18% (p<0.05)]. Multivariable analysis revealed that the use of ≥30 mL/Kg fluid bolus decreased the chances of mortality by 12% [OR 0.88, 95% CI 0.82-0.95 (p<0.05)]. The use of ≥30 mL/Kg fluid bolus did not increase the odds of mechanical ventilation [OR 0.99, 95% CI 0.93-1.05 (p = 0.78)]. In subgroup analysis, the use of ≥30 mL/Kg fluid bolus decreased the chances of mortality by 5% [OR 0.95, 95% CI 0.90-0.99, (p<0.05)] and did not increase the odds of mechanical ventilation. The presence of the low ejection fraction did not influence the chance of getting fluid bolus.ConclusionThe use of ≥30 mL/Kg fluid bolus seems to confer protection against in-hospital mortality and is not associated with increased chances of mechanical ventilation in heart failure patients presenting with severe sepsis or septic shock.

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Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study.

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Effects of discontinuing or continuing ongoing statin therapy in severe sepsis and septic shock: a retrospective cohort study.

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