'Relation, association, attribution ...' – the multiple faces of death in critical care medicine

Mortality is one of the most important quality markers in critical care, and there have been many epidemiological studies trying to identify risk factors to better understand the mechanisms leading to death in this complex disease. One of the major problems is that there are multiple factors contributing to fatal outcome of septic patients, and it is difficult to distinguish between those that are independent from the acute disease (comorbidities and 'risk factors') and those that are directly involved in the pathomechanisms of sepsis, thus leading to the 'sepsis-attributable' mortality. In this short commentary, some examples of different approaches of how to analyze data on mortality are presented

Managing septic shock

Although several successful clinical trials in the last 2-3 years have been greeted with enthusiasm by intensivists, severe sepsis and septic shock still have increasing incidence and more or less unchanged mortality. Within the last few years, the progress in sepsis research covering definitions, epidemiology, pathophysiology, diagnosis, and standard and adjunctive therapy as well as general measures such as treatment bundles is encouraging. In this report, a small selection of recent publications, focusing on the current discussion of activated protein C as well as the relevance of the Surviving Sepsis Campaign bundle therapy, is presented and the possible impact on clinical routine is discussed

An international sepsis survey: a study of doctors' knowledge and perception about sepsis

BACKGROUND: To be able to diagnose and treat sepsis better it is important not only to improve the knowledge about definitions and pathophysiology, but also to gain more insight into specialists' perception of, and attitude towards, the current diagnosis and treatment of sepsis. METHODS: The study was conducted as a prospective, international survey by structured telephone interview. The subjects were intensive care physicians and other specialist physicians caring for intensive care unit (ICU) patients. RESULTS: The 1058 physicians who were interviewed (including 529 intensivists) agreed that sepsis is a leading cause of death on the ICU and that the incidence of sepsis is increasing, but that the symptoms of sepsis can easily be misattributed to other conditions. Physicians were concerned that this could lead to under-reporting of sepsis. Two-thirds (67%) were concerned that a common definition is lacking and 83% said it is likely that sepsis is frequently missed. Not more than 17% agreed on any one definition. CONCLUSION: There is a general awareness about the inadequacy of the current definitions of sepsis. Physicians caring for patients with sepsis recognise the difficulty of defining and diagnosing sepsis and are aware that they miss the diagnosis frequently

Adhesion molecules in different treatments of acute myocardial infarction

BACKGROUND: Tissue damage after ischemia and reperfusion involves leukocyte endothelial interactions mediated by cell adhesion molecules. This study was designed to determine the time course of soluble adhesion molecules in patients with acute myocardial infarction after attempted reperfusion by thrombolysis with tissue plasminogen activator (tPA) or streptokinase (SK), or percutaneous transluminal coronary angioplasty (PTCA). METHODS: In 3 × 10 randomly selected patients with acute myocardial infarction undergoing thrombolysis with tPA or SK, or treated with PTCA, plasma concentrations of soluble L-selectin, P-selectin, E-selectin, intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1) were measured by enzyme-linked immunosorbent assay, 30 min and 1, 2, 4, 8, 12 and 24 hours after intervention. RESULTS: After thrombolysis with tPA, soluble L-selectin concentrations were persistently depressed and soluble PECAM-1 concentrations were elevated, compared with controls, SK and PTCA. While soluble VCAM-1 concentrations did not differ within the first hours after interventions between the three groups, soluble VCAM-1 rose by 24 hours after tPA thrombolysis but did not increase after SK and PTCA treatment. Soluble ICAM-1 concentrations were consistently elevated after PTCA compared with controls and thrombolysed patients. Soluble E-selectin was depressed after tPA thrombolysis and PTCA in comparison with controls, while the SK group showed an increase throughout the observation period. Soluble P-selectin was increased after PTCA and SK lysis up to 8 hours after treatment compared with controls, but no significant differences could be found between treatment groups. CONCLUSION: Adhesion molecules mediating leukocyte endothelial interactions are altered subsequent to postischemic reperfusion and by treatment with thrombolytic agents and angioplasty. The clinical relevance of these biological changes remains to be determined

The PIRO concept: P is for predisposition

SCOPUS: cp.jinfo:eu-repo/semantics/publishe

Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study

INTRODUCTION: Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome. METHODS: In a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay. RESULTS: Of 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001). CONCLUSION: Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients

Pathway deregulation and expression QTLs in response to Actinobacillus pleuropneumoniae infection in swine

Actinobacillus (A.) pleuropneumoniae is among the most important pathogens in pig. The agent causes severe economic losses due to decreased performance, the occurrence of acute or chronic pleuropneumonia, and an increase in death incidence. Since therapeutics cannot be used in a sustainable manner, and vaccination is not always available, new prophylactic measures are urgently needed. Recent research has provided evidence for a genetic predisposition in susceptibility to A. pleuropneumoniae in a Hampshire × German Landrace F2 family with 170 animals. The aim of the present study is to characterize the expression response in this family in order to unravel resistance and susceptibility mechanisms and to prioritize candidate genes for future fine mapping approaches. F2 pigs differed distinctly in clinical, pathological, and microbiological parameters after challenge with A. pleuropneumoniae. We monitored genome-wide gene expression from the 50 most and 50 least susceptible F2 pigs and identified 171 genes differentially expressed between these extreme phenotypes. We combined expression QTL analyses with network analyses and functional characterization using gene set enrichment analysis and identified a functional hotspot on SSC13, including 55 eQTL. The integration of the different results provides a resource for candidate prioritization for fine mapping strategies, such as TF, TFRC, RUNX1, TCN1, HP, CD14, among others