Philipp Schuetz

Procalcitonin to Guide Initiation and Duration of Antibiotic Treatment in Acute Respiratory Infections: An Individual Patient Data Meta-Analysis

This individual patient data meta-analysis of clinical trials investigating procalcitonin algorithms for antibiotic decision making found no increased risk of death or setting-specific treatment failure but did find significantly lower antibiotic exposure across different acute respiratory infections and clinical settings.

Circulating levels of copeptin, a novel biomarker, in lower respiratory tract infections.

Backgroundu2002 Vasopressin has haemodynamic as well as osmoregulatory effects, and reflects the individual stress response. Copeptin is cosynthesized with vasopressin, directly mirroring vasopressin levels, but is more stable in plasma and serum. Both levels are increased in patients with septic shock. Lower respiratory tract infections (LRTI) are a precursor of sepsis. Thus, we investigated circulating levels and the prognostic use of copeptin for the severity and outcome in patients with LRTI.

The association of endothelial cell signaling, severity of illness, and organ dysfunction in sepsis

IntroductionPrevious reports suggest that endothelial activation is an important process in sepsis pathogenesis. We investigated the association between biomarkers of endothelial cell activation and sepsis severity, organ dysfunction sequential organ failure assessment (SOFA) score, and death.MethodsThis is a prospective, observational study including adult patients (age 18 years or older) presenting with clinical suspicion of infection to the emergency department (ED) of an urban, academic medical center between February 2005 and November 2008. Blood was sampled during the ED visit and biomarkers of endothelial cell activation, namely soluble fms-like tyrosine kinase-1 (sFlt-1), plasminogen activator inhibitors -1 (PAI-1), sE-selectin, soluble intercellular adhesion molecule (sICAM-1), and soluble vascular cell adhesion molecule (sVCAM-1), were assayed. The association between biomarkers and the outcomes of sepsis severity, organ dysfunction, and in-hospital mortality were analyzed.ResultsA total of 221 patients were included: sepsis without organ dysfunction was present in 32%, severe sepsis without shock in 30%, septic shock in 32%, and 6% were non-infected control ED patients. There was a relationship between all target biomarkers (sFlt-1, PAI-1, sE-selectin, sICAM-1, and sVCAM-1) and sepsis severity, P < 0.05. We found a significant inter-correlation between all biomarkers, including the strongest correlations between sFlt-1 and sE-selectin (r = 0.55, P < 0.001), and between sFlt-1 and PAI-1 (0.56, P < 0.001). Among the endothelial cell activation biomarkers, sFlt-1 had the strongest association with SOFA score (r = 0.66, P < 0.001), the highest area under the receiver operator characteristic curve for severe sepsis of 0.82, and for mortality of 0.91.ConclusionsMarkers of endothelial cell activation are associated with sepsis severity, organ dysfunction and mortality. An improved understanding of endothelial response and associated biomarkers may lead to strategies to more accurately predict outcome and develop novel endothelium-directed therapies in sepsis.

Serum procalcitonin, C-reactive protein and white blood cell levels following hypothermia after cardiac arrest: a retrospective cohort study.

Eur J Clin Invest 2010; 40 (4): 376–381

Initial Management of Septic Patients with Hyperglycemia in the Noncritical Care Inpatient Setting

BACKGROUNDnPrevious research on the management of hyperglycemia in patients with sepsis has focused primarily on those with established organ failure in the critical care setting. The impact of hyperglycemia and glycemic control in patients with infection before developing severe sepsis or shock remains undefined.nnnMETHODSnThis observational, prospective, cohort study investigated the relationship between initial 72-hour time-weighted mean glucose concentrations and in-hospital mortality, intensive care unit transfer, and hospital length of stay in a cohort of patients with an acute infection who were admitted from the emergency department to a non-intensive care unit hospital ward. We used multivariate regression models adjusted for age, diabetes, and disease severity.nnnRESULTSnA total of 1849 patients were included, of whom 29% had diabetes. In the 1310 nondiabetic patients, we observed hyperglycemia using time-weighted glucose concentrations: 121 to 150 mg/dL (n=204, 16%), 151 to 180 mg/dL (n=32, 2.4%), and greater than 180 mg/dL (n=21, 1.6%). Insulin treatment was infrequent in nondiabetic patients, with 9%, 13%, and 29% of nondiabetic patients in these ranges receiving insulin, respectively. As patient glucose values increased, in-hospital mortality increased in nondiabetic patients, with odds ratios (ORs) of 4.4 (95% confidence interval [CI], 1.8-11), 10.0 (95% CI, 2.5-40), and 9.3 (95% CI, 1.9-44.0). Conversely, hyperglycemia did not confer an increased risk of adverse outcomes in diabetic patients. Likewise, increased risk for unplanned intensive care unit admission from the floor demonstrated ORs of 2.2 (95% CI, 1.1-4.3), 2.0 (95% CI, 0.45-8.9), and 6.3 (95% CI, 1.9-20.6) in nondiabetic patients, whereas no increased risk was found in diabetic patients.nnnCONCLUSIONSnIn this cohort of acutely infected patients without established severe sepsis or shock, higher glucose concentrations within the first 72 hours in the nondiabetic population were associated with worse hospital outcomes and were less likely to be treated with insulin compared with diabetic patients.

Diabetes is not associated with increased mortality in emergency department patients with sepsis.

STUDY OBJECTIVEnDespite its high prevalence, the influence of diabetes on outcomes of emergency department (ED) patients with sepsis remains undefined. Our aim is to investigate the association of diabetes and initial glucose level with mortality in patients with suspected infection from the ED.nnnMETHODSnThree independent, observational, prospective cohorts from 2 large US tertiary care centers were studied. We included patients admitted to the hospital from the ED with suspected infection. We investigated the association of diabetes and inhospital mortality within each cohort separately and then overall with logistic regression and generalized estimating equations adjusted for age, sex, disease severity, and sepsis syndrome. We also tested for an interaction between diabetes and hyperglycemia/hypoglycemia.nnnRESULTSnA total of 7,754 patients were included. The mortality rate was 4.3% (95% confidence interval [CI] 3.9% to 4.8%) and similar in diabetic and nondiabetic patients (4.1% versus 4.4%; absolute risk difference 0.4%; 95% CI -0.7% to 1.4%). There was no significant association between diabetes and mortality in adjusted analysis (odds ratio [OR] overall 0.85; 95% CI 0.71 to 1.01). Diabetes significantly modified the effect of hyperglycemia and hypoglycemia with mortality; initial glucose levels greater than 200 mg/dL were associated with higher mortality in nondiabetic patients (OR 2.1; 95% CI 1.4 to 3.0) but not in diabetic patients (OR 1.0; 95% CI 0.2 to 4.7), whereas glucose levels less than 100 mg/dL were associated with higher mortality mainly in the diabetic population (OR 2.3; 95% CI 1.6 to 3.3) and to a lesser extent in nondiabetic patients (OR 1.1; 95% CI 1.03 to 1.14).nnnCONCLUSIONnWe found no evidence for a harmful association of diabetes and mortality in patients across different sepsis severities. High initial glucose levels were associated with adverse outcomes in the nondiabetic population only. Further investigation is warranted to determine the mechanism for these effects.

Influence of diabetes on endothelial cell response during sepsis

Aims/hypothesisSeveral endothelial pathways of cell adhesion, coagulation and vascular endothelial growth factor (VEGF) signalling are activated during sepsis. The objective of this analysis was to investigate the influence of diabetes on biomarkers of endothelial cell activation in sepsis.MethodsThis was a prospective observational cohort study of a convenience sample of adult patients (age ≥u200918xa0years) for whom infection was clinically suspected and who presented to an urban tertiary care emergency department between February 2005 and November 2008. We investigated the association of diabetes and sepsis with various endothelial activation biomarkers of cell adhesion (E-selectin, vascular cell adhesion molecule 1 [VCAM-1] and intercellular adhesion molecule 1 [ICAM-1]), coagulation (plasminogen activator inhibitor 1 [PAI-1]) and VEGF signalling (soluble fms-like tyrosine kinase-1 [sFLT-1]).ResultsA total of 207 patients (34% with sepsis, 32% with severe sepsis and 34% with septic shock) were studied, including 63 (30%) with diabetes. Compared with patients without diabetes, patients with diabetes had significantly increased E-selectin and sFLT-1 levels overall; this was most pronounced during septic shock in the stratified analysis. Multivariate models including age, sex, sepsis severity and other variables as potential covariates confirmed the association of diabetes with elevated circulating plasma levels of E-selectin (standardised β 0.24, pu2009<u20090.001) and sFLT-1 (standardised β 0.19, pu2009<u20090.01), but there was no significant association with VCAM-1, ICAM-1 or PAI-1.Conclusions/interpretationDuring septic shock, patients with diabetes had higher levels of circulating biomarkers of endothelial cell adhesion (E-selectin) and VEGF signalling (sFLT-1). Future studies should address whether enhanced activation of the endothelium places patients with diabetes at increased risk for the development of sepsis and worsening morbidity and mortality.