Project description: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.
Project description:Morbidity and mortality from sepsis remains unacceptably high. Large variability in clinical practice, plus the increasing awareness that certain processes of care associated with improved critical care outcomes, has led to the development of clinical practice guidelines in a variety of areas related to infection and sepsis. The Surviving Sepsis Guidelines for Management of Severe Sepsis and Septic Shock were first published in 2004, revised in 2008, and recently revised again and published in 2013. The first part of this manuscript is a summary of the 2013 guidelines with some editorial comment. The second part of the manuscript characterizes hospital based sepsis performance improvement programs and highlights the sepsis bundles from the Surviving Sepsis Campaign as a key component of such a program.
Project description:ObjectiveOur primary aim was to assess selected metabolic dysfunction parameters, both independently and as a complement to the SOFA score, as predictors of short-term mortality in patients with infection admitted to the intensive care unit (ICU).MethodsWe retrospectively enrolled all consecutive adult patients admitted to the eight ICUs of Lille University Hospital, between January 2015 and September 2016, with suspected or confirmed infection. We selected seven routinely measured biological and clinical parameters of metabolic dysfunction (maximal arterial lactatemia, minimal and maximal temperature, minimal and maximal glycaemia, cholesterolemia, and triglyceridemia), in addition to age and the Charlson's comorbidity score. All parameters and SOFA scores were recorded within 24 h of admission.ResultsWe included 956 patients with infection, among which 295 (30.9%) died within 90 days. Among the seven metabolic parameters investigated, only maximal lactatemia was associated with higher risk of 90-day hospital mortality in SOFA-adjusted analyses (SOFA-adjusted OR, 1.17; 95%CI, 1.10 to 1.25; p < 0.001). Age and the Charlson's comorbidity score were also statistically associated with a poor prognosis in SOFA-adjusted analyses. We were thus able to develop a metabolic failure, age, and comorbidity assessment (MACA) score based on scales of lactatemia, age, and the Charlson's score, intended for use in combination with the SOFA score.ConclusionsThe maximal lactatemia level within 24 h of ICU admission is the best predictor of short-term mortality among seven measures of metabolic dysfunction. Our combined "SOFA + MACA" score could facilitate early detection of patients likely to develop severe infections. Its accuracy requires further evaluation.
Project description:BACKGROUND:Tocilizumab (TCZ), a humanized monoclonal antibody targeting the interleukin-6 (IL-6) receptor, has been proposed for the treatment of COVID-19 patients; however, limited data are available on the safety and efficacy. METHODS:We performed a retrospective study on severe COVID-19 patients with hyper-inflammatory features admitted outside intensive care units (ICUs). Patients treated with intravenous TCZ in addition to standard of care were compared to patients treated with standard of care alone. Safety and efficacy were assessed over a 28-day follow-up. RESULTS:65 patients were included. Among them, 32 were treated with TCZ. At baseline, all patients were on high-flow supplemental oxygen and most (78% of TCZ patients and 61% of standard treatment patients) were on non-invasive ventilation. During the 28-day follow-up, 69% of TCZ patients experienced a clinical improvement compared to 61% of standard treatment patients (p = 0.61). Mortality was 15% in the tocilizumab group and 33% in standard treatment group (p = 0.15). In TCZ group, at multivariate analysis, older age was a predictor of death, whereas higher baseline PaO2:FiO2 was a predictor of clinical improvement at day 28. The rate of infection and pulmonary thrombosis was similar between the two groups. CONCLUSIONS:At day 28, clinical improvement and mortality were not statistically different between tocilizumab and standard treatment patients in our cohort. Bacterial or fungal infections were recorded in 13% of tocilizumab patients and in 12% of standard treatment patients. Confirmation of efficacy and safety will require ongoing controlled trials.
Project description:BackgroundSepsis has several clinical stages, and mortality rates are different for each stage. Our goal was to establish the evolution and the determinants of the progression of clinical stages, from infection to septic shock, over the first week, as well as their relationship to 7-day and 28-day mortality.MethodsThis is a secondary analysis of a multicenter cohort of inpatients hospitalized in general wards or intensive care units (ICUs). The general estimating equations (GEE) model was used to estimate the risk of progression and the determinants of stages of infection over the first week. Cox regression with time-dependent covariates and fixed covariates was used to determine the factors related with 7-day and 28-day mortality, respectively.ResultsIn 2681 patients we show that progression to severe sepsis and septic shock increases with intraabdominal and respiratory sources of infection [OR = 1,32; 95%IC = 1,20-1,46 and OR = 1.21, 95%CI = 1,11-1,33 respectively], as well as according to Acute Physiology and Chronic Health Evaluation II (APACHE II) [OR = 1,03; 95%CI = 1,02-1,03] and Sequential Organ Failure Assessment (SOFA) [OR = 1,16; 95%CI = 1,14-1,17] scores. The variables related with first-week mortality were progression to severe sepsis [HR = 2,13; 95%CI = 1,13-4,03] and septic shock [HR = 3,00; 95%CI = 1,50-5.98], respiratory source of infection [HR = 1,76; 95%IC = 1,12-2,77], APACHE II [HR = 1,07; 95% CI = 1,04-1,10] and SOFA [HR = 1,09; 95%IC = 1,04-1,15] scores.ConclusionsIntraabdominal and respiratory sources of infection, independently of SOFA and APACHE II scores, increase the risk of clinical progression to more severe stages of sepsis; and these factors, together with progression of the infection itself, are the main determinants of 7-day and 28-day mortality.
Project description:For more than two decades, sepsis was defined as a microbial infection that produces fever (or hypothermia), tachycardia, tachypnoea and blood leukocyte changes. Sepsis is now increasingly being considered a dysregulated systemic inflammatory and immune response to microbial invasion that produces organ injury for which mortality rates are declining to 15-25%. Septic shock remains defined as sepsis with hyperlactataemia and concurrent hypotension requiring vasopressor therapy, with in-hospital mortality rates approaching 30-50%. With earlier recognition and more compliance to best practices, sepsis has become less of an immediate life-threatening disorder and more of a long-term chronic critical illness, often associated with prolonged inflammation, immune suppression, organ injury and lean tissue wasting. Furthermore, patients who survive sepsis have continuing risk of mortality after discharge, as well as long-term cognitive and functional deficits. Earlier recognition and improved implementation of best practices have reduced in-hospital mortality, but results from the use of immunomodulatory agents to date have been disappointing. Similarly, no biomarker can definitely diagnose sepsis or predict its clinical outcome. Because of its complexity, improvements in sepsis outcomes are likely to continue to be slow and incremental.
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:IntroductionAlthough metabolic alkalosis is a common occurrence in intensive care units (ICUs), no study has evaluated its prevalence or outcomes in patients with severe sepsis or septic shock.MethodsThis is a retrospective cohort study of critically ill patients suffering from severe sepsis and septic shock admitted to the ICUs of Halmstad and Varberg County hospitals. From 910 patient records, 627 patients met the inclusion criteria. We investigated the relationship between metabolic alkalosis and mortality. Further, we studied the relationship between metabolic alkalosis and ICU length of stay (LOS).ResultsMetabolic alkalosis was associated with decreased 30-day and 12-month mortalities. This effect was however lost when a multivariate analysis was conducted, correcting for age, gender, pH on admission, base excess (BE) on admission, Simplified Acute Physiology Score III (SAPS III) and acute kidney injury (AKI). We then analyzed for any dose-response effect between the severity of metabolic alkalosis and mortality and found no relationship. Bivariate analysis showed that metabolic alkalosis had a significant effect on the length of ICU stay. When adjusting for age, sex, pH at admission, BE at admission, SAPS III and AKI in a multivariate analysis, metabolic alkalosis significantly contributed to prolonged ICU length of stay. In two separate sensitivity analyses pure metabolic alkalosis and late metabolic alkalosis (time of onset >48 hours) were the only significant predictor of increased ICU length of stay.ConclusionMetabolic alkalosis did not have any effect on 30-day and 12-month mortalities after adjusting for age, sex, SAPS III-score, pH and BE on admission and AKI in a multivariate analysis. The presence of metabolic alkalosis was independently associated with an increased ICU length of stay.
Project description:OBJECTIVE:To describe the effect of liver disease (LD) on lactate clearance during early sepsis resuscitation. METHODS:This is a multicenter randomized clinical trial. An initial lactate >2 mmol/L and subsequent serum lactate measurement within 6 hours were required for inclusion. LD was categorized by two methods: 1) past medical history (PMH) categorized as no LD, mild LD (no Child's score criteria, but PMH of hepatitis B/C), cirrhosis; and 2) measurable liver dysfunction determined by the liver component of the sequential organ failure assessment (L-SOFA) score as no dysfunction (L-SOFA score 0), mild dysfunction (score 1), moderate-severe dysfunction (score 2 to 4). Primary outcome was the rate of lactate normalization. RESULTS:One hundred eighty-seven patients were included. When categorized by PMH, 169 patients had no LD, 6 mild LD, and 12 cirrhosis. 63/169 (37%) of patients with no LD achieved lactate normalization, compared to 4/6 (67%) with mild LD, and 1/12 (8%) with cirrhosis (P<0.03). Categorized by L-SOFA score, 59/124 (47%) patients with L-SOFA 0 achieved lactate normalization, compared to 6/31 (19%) with L-SOFA 1, and 3/32 (9%) with L-SOFA 2-4 (P<0.01). Relative lactate clearance [(initial lactate-subsequent lactate)/initial lactate] was lower in patients with more advanced LD by PMH (37.7 vs. 40.4 vs. 21.8, P=0.07), and lower with increasing L-SOFA score (42.0 vs. 30.1 vs. 23.4, P=0.01). CONCLUSION:Liver dysfunction was significantly associated with impaired lactate clearance and normalization during the early resuscitation of sepsis.
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.