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Angiopoietin Level Trajectories in Toddlers With Severe Sepsis and Septic Shock and Their Effect on Capillary Endothelium.

ABSTRACT: OBJECTIVE:Angiopoietins are postulated diagnostic biomarkers in children and adults with severe sepsis and septic shock. The diagnostic value of angiopoietins in children less than 5 years old has not been established, nor has their effect on permeability in the capillary microvasculature. We aim to determine if levels of angiopoietin-1 or -2 (angpt-1, -2) are diagnostic for severe sepsis/shock in young children and whether they affect the permeability of cultured human dermal microvascular endothelial cells (HDMEC). DESIGN:Prospective observational study of children < 5 years old. Patients were classified as non-systemic inflammatory response syndrome (SIRS), SIRS/sepsis and severe sepsis/septic shock. SETTING:Tertiary care pediatric hospitals. PATIENTS:Critically ill children. INTERVENTIONS:None. MEASUREMENTS:Plasma angpt-1 and -2 levels were measured with enzyme-linked immunoassays. Expression of angpt-2 in endothelial cells was assessed with quantitative polymerase chain reaction. Permeability changes in cultured HDMECs were assessed with transendothelial electrical resistance measurements. RESULTS:Angpt-1 levels were significantly higher in younger children compared with levels found in previous study of older children across disease severity (all P?

SUBMITTER: Pierce RW

PROVIDER: S-EPMC6375782 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Angiopoietin Level Trajectories in Toddlers With Severe Sepsis and Septic Shock and Their Effect on Capillary Endothelium.

Pierce Richard W RW Shabanova Veronika V Canarie Michael M Pinto Mathew M da Silva Yong Sing YS Bhandari Vineet V Giuliano John S JS

Shock (Augusta, Ga.) 20190301 3

<h4>Objective</h4>Angiopoietins are postulated diagnostic biomarkers in children and adults with severe sepsis and septic shock. The diagnostic value of angiopoietins in children less than 5 years old has not been established, nor has their effect on permeability in the capillary microvasculature. We aim to determine if levels of angiopoietin-1 or -2 (angpt-1, -2) are diagnostic for severe sepsis/shock in young children and whether they affect the permeability of cultured human dermal microvascu ...[more]

PMID: 30286031

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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:ObjectivesTo assess the variability in short-term sepsis mortality by hospital among Centers for Medicare and Medicaid Services beneficiaries in the United States during 2013-2014.DesignA retrospective cohort design.SettingHospitalizations from 3,068 acute care hospitals that participated in the Centers for Medicare and Medicaid Services inpatient prospective payment system in 2013 and 2014.PatientsMedicare fee-for-service beneficiaries greater than or equal to 65 years old who had an inpatient hospitalization coded with present at admission severe sepsis or septic shock.InterventionsNone.Measurements and main resultsIndividual level mortality was assessed as death at or within 7 days of hospital discharge and aggregated to calculate hospital-level mortality rates. We used a logistic hierarchal linear model to calculate mortality risk-adjusted for patient characteristics. We quantified variability among hospitals using the median odds ratio and calculated risk-standardized mortality rates for each hospital. The overall crude mortality rate was 34.7%. We found significant variability in mortality by hospital (p < 0.001). The middle 50% of hospitals had similar risk-standardized mortality rates (32.7-36.9%), whereas the decile of hospitals with the highest risk-standardized mortality rates had a median mortality rate of 40.7%, compared with a median of 29.2% for hospitals in the decile with the lowest risk-standardized mortality rates. The median odds ratio (1.29) was lower than the adjusted odds ratios for several measures of patient comorbidities and severity of illness, including present at admission organ dysfunction, no identified source of infection, and age.ConclusionsIn a large study of present at admission sepsis among Medicare beneficiaries, we showed that mortality was most strongly associated with underlying comorbidities and measures of illness on arrival. However, after adjusting for patient characteristics, mortality also modestly depended on where a patient with sepsis received care, suggesting that efforts to improve sepsis outcomes in lower performing hospitals could impact sepsis survival.

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.

Dataset Information

Angiopoietin Level Trajectories in Toddlers With Severe Sepsis and Septic Shock and Their Effect on Capillary Endothelium.

Publications

Angiopoietin Level Trajectories in Toddlers With Severe Sepsis and Septic Shock and Their Effect on Capillary Endothelium.

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