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The aPC treatment improves microcirculation in severe sepsis/septic shock syndrome.

ABSTRACT: 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?

SUBMITTER: Donati A

PROVIDER: S-EPMC3848895 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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The aPC treatment improves microcirculation in severe sepsis/septic shock syndrome.

Donati Abele A Damiani Elisa E Botticelli Laura L Adrario Erica E Lombrano Maria Rita MR Domizi Roberta R Marini Benedetto B Van Teeffelen Jurgen Wge JW Carletti Paola P Girardis Massimo M Pelaia Paolo P Ince Can C

BMC anesthesiology 20130926 1

<h4>Background</h4>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.<h4>Methods</h4>Prospective observational study on patients admitted in a 12-beds intensive care unit of a university hospital from July 2010 t ...[more]

PMID: 24070065

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Project description:BackgroundIn randomised controlled trials, procalcitonin (PCT)-guided antibiotic treatment has been proven to significantly reduce length of antibiotic therapy in intensive care unit (ICU) patients. However, concern was raised on low protocol adherence and high rates of overruling, and thus the value of PCT-guided treatment in real clinical life outside study conditions remains unclear. In this study, adherence to a PCT protocol to guide antibiotic treatment in patients with severe sepsis and septic shock was analysed.MethodsFrom 2012 to 2014, surgical ICU patients with severe sepsis or septic shock were retrospectively screened for PCT measurement series appropriate to make treatment decisions on antibiotic therapy. We compared (1) patients with appropriate PCT measurement series to patients without appropriate series; (2) patients who reached the antibiotic stopping advice threshold (PCT < 0.5 ng/mL and/or decrease to 10% of peak level) to patients who did not reach a stopping advice threshold; and (3) patients who were treated adherently to the PCT protocol to non-adherently treated patients. The groups were compared in terms of antibiotic treatment duration, PCT kinetics, and other clinical outcomes.ResultsOf 81 patients with severe sepsis or septic shock, 14 were excluded due to treatment restriction or short course in the ICU. The final analysis was performed on 67 patients. Forty-two patients (62.7%) had appropriate PCT measurement series. In patients with appropriate PCT series, median initial PCT (p = 0.001) and peak PCT levels (p < 0.001) were significantly higher compared to those with non-appropriate series. In 26 patients with appropriate series, PCT levels reached an antibiotic stopping advice. In 8 of 26 patients with stopping advice, antibiotics were discontinued adherently to the PCT protocol (30.8%). Patients with adherently discontinued antibiotics had a shorter antibiotic treatment (7d [IQR 6-9] vs. 12d [IQR 9-16]; p = 0.002). No differences were seen in terms of other clinical outcomes.ConclusionIn patients with severe sepsis and septic shock, procalcitonin testing was irregular and adherence to a local PCT protocol was low in real clinical life. However, adherently treated patients had a shorter duration of antibiotic treatment without negative clinical outcomes. Procalcitonin peak values and kinetics had a clear impact on the regularity of PCT testing.

Project description:ObjectivesTo assess the prevalence of immunocompromised diagnoses among children with severe sepsis and septic shock, and to determine the association between immunocompromised diagnoses and clinical outcomes after adjustment for demographics and illness severity.DesignRetrospective multicenter cohort study.SettingEighty-three centers in the Virtual Pediatric Systems database.PatientsChildren with severe sepsis or septic shock admitted to a participating PICU between January 1, 2012, and December 31, 2016.InterventionsNone.Measurements and main resultsAcross 83 centers, we identified 10,768 PICU admissions with an International Classification of Diseases, 9th Revision, Clinical Modification code for severe sepsis or septic shock; 3,021 of these patients (28%) had an immunocompromised diagnosis. To evaluate variation across centers and determine factors associated with PICU mortality, we used mixed-effect logistic regression models. Among patients without hematopoietic cell transplant, congenital immunodeficiency (adjusted odds ratio, 1.90; 95% CI, 1.24-2.92), multiple prior malignancies (adjusted odds ratio, 1.86; 95% CI, 1.15-2.99), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 3.09; 95% CI, 1.91-4.98) were associated with an increased odds of PICU mortality. Among patients with prior hematopoietic cell transplant, liquid malignancy (adjusted odds ratio, 3.15; 95% CI, 2.09-4.74), congenital immunodeficiency (adjusted odds ratio, 6.94; 95% CI, 3.84-12.53), multiple prior malignancies (adjusted odds ratio, 3.54; 95% CI, 1.80-6.95), and hemophagocytic lymphohistiocytosis (adjusted odds ratio, 2.79; 95% CI, 1.36-5.71) were associated with an increased odds of PICU mortality. PICU mortality varied significantly by center, and a higher mean number of sepsis patients per month in a center was associated with lower PICU mortality (adjusted odds ratio, 0.94; 95% CI, 0.90-0.98). PICU resource utilization varied by immunocompromised diagnosis and history of hematopoietic cell transplant, and among survivors immunocompromised patients have shorter median PICU length of stay compared with patients without immunocompromised diagnoses (p < 0.001).ConclusionsImmunocompromised diagnoses are present in 28% of children with severe sepsis or septic shock. Multiple prior malignancies, hemophagocytic lymphohistiocytosis, congenital immunodeficiency, and hematopoietic cell transplant are independently associated with an increased odds of PICU mortality in children with severe sepsis or septic shock. Significant variation exists in PICU mortality among centers despite adjustment for immunocompromised diagnoses, known risk factors for sepsis-related mortality, and center-level sepsis volume.

Project description:BackgroundProspective studies on the incidence of VTE during severe sepsis and septic shock remain absent, hindering efficacy assessments regarding VTE prevention strategies in sepsis.MethodsWe prospectively studied 113 consecutively enrolled patients in the ICU with severe sepsis and septic shock at three hospitals. All patients provided informed consent. VTE thromboprophylaxis was recorded for all patients. Patients underwent ultrasonography and were followed for VTE prior to ICU discharge. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with VTE (including central venous catheter [CVC] insertion, age, length of stay, and mechanical ventilation) were included in a multivariable logistic regression analysis using backward stepwise elimination to determine VTE predictors.ResultsMean APACHE (Acute Physiology and Chronic Health Evaluation) II score was 18.2 ± 7.0, and age was 50 ± 18 years. Despite all patients receiving guideline-recommended thromboprophylaxis, the incidence of VTE was 37.2% (95% CI, 28.3-46.8). Most VTE events were clinically significant (defined as pulmonary embolism, proximal DVT, and/or symptomatic distal DVT) and associated with an increased length of stay (18.2 ± 9.9 days vs 13.4 ± 11.5 days, P < .05). Mortality was higher in patients with acute VTE but did not reach statistical significance. Insertion of a CVC and longer mechanical ventilation duration were significant VTE risk factors. VTE incidence did not differ by thromboprophylaxis type.ConclusionsTo our knowledge this is the first multicenter prospective study to identify a high incidence of VTE in patients with severe sepsis and septic shock, despite the use of universal, guideline-recommended thromboprophylaxis. Our findings suggest that the systemic inflammatory milieu of sepsis may uniquely predispose patients with sepsis to VTE. More effective VTE prevention strategies are necessary in patients with sepsis.Trial registryClinicalTrials.gov; No.: NCT02353910; URL: www.clinicaltrials.gov.

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The aPC treatment improves microcirculation in severe sepsis/septic shock syndrome.

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The aPC treatment improves microcirculation in severe sepsis/septic shock syndrome.

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