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Purpose Endothelial protein C receptor (EPCR) is expressed mainly in endothelial cells and is involved in regulation of the cytoprotective and anticoagulant pathways of protein C. We assessed whether haplotypes in the EPCR gene modify the risk of severe sepsis and/or septic shock (SS/SS) development in critically ill patients. Methods Three polymorphisms in the EPCR gene were genotyped in 389 Caucasian critically ill patients, hospitalized in the intensive care units of two major hospitals in Athens, Greece. Multivariate logistic regression analysis controlling for age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, sex, and diagnosis was performed to determine the effect of haplotypes H1 and H3 in the EPCR gene on the development of SS/SS. Results H2 carriers versus all other genotypes combined had a nonsignificant excess of SS/SS (p = 0.087). SS/SS occurred in 38.8 % of critically ill patients carrying minor alleles belonging to both H1 and H3 haplotypes, in 58.0 % of H1 carriers, 64.3 % of H3 carriers, and 65.2 % of patients carrying all common alleles (H2). Compared with H2 carriers, the odds ratios (OR) for developing SS/SS were 0.34 [95 % confidence interval (CI) 0.16–0.76, p = 0.008] for simultaneous H1 and H3 carriers, 0.65 (95 % CI 0.37–1.13, p = 0.123) for H1 carriers, and 0.82 (95 % CI 0.39–1.70, p = 0.590) for H3 carriers. Conclusions Our results indicate that simultaneous carriers of minor alleles belonging to both the H1 and H3 haplotypes may be at reduced risk of developing SS/SS in this cohort of critically ill patients.

The aim of this study was to explore the effect of red blood cell (RBC) transfusion on microdialysis-assessed interstitial fluid metabolic parameters in septic patients. We conducted a retrospective study of 37 patients with severe sepsis/septic shock requiring transfusion of one to two RBC units. Interstitial fluid metabolic alterations were monitored by a microdialysis catheter inserted in the subcutaneous adipose tissue. Samples were collected before (T0) and after transfusion at two time-points: T1a and T1b; median post-transfusion times of 120 [interquartile range (IQR); 45–180] and 360 (IQR; 285–320) min. Lactate, pyruvate, glycerol and glucose concentrations were measured with a bedside analyzer, and the lactate/pyruvate (LP) ratio was calculated automatically. RBC transfusions decreased the LP ratio from (T0) 18.80 [interquartile range (IQR); 14.85–27.45] to (T1a) 17.80 (IQR; 14.35–25.20; P

To investigate the pattern of pituitary-adrenal responses to human corticotropin-releasing hormone (hCRH) in critically ill patients and to examine the relation between responses and clinical outcome.Prospective study in consecutive critically ill patients in a general intensive care unit in a teaching hospital.The study included 37 critically ill, mechanically ventilated patients with diverse underlying diagnoses (28 men, 9 women; median age 56 years).A morning blood sample was obtained to measure baseline cortisol, corticotropin (ACTH), and cytokines. Patients were then injected with 100 microg hCRH, and plasma cortisol and ACTH were measured over a period of 2 h.In the overall patient population baseline and peak cortisol concentrations following hCRH were 16+/-5 and 21+/-5 microg/dl, respectively, and median baseline and peak ACTH levels 23 and 65 pg/ml, respectively. Higher ACTH levels and longer release of cortisol were noted in nonsurvivors (n=18) than in survivors (n=19). Furthermore, nonsurvivors had higher concentrations of interleukin 8 (115 vs. 38 pg/ml) and interleukin 6 (200 vs. 128 pg/ml) than survivors.Critically ill patients demonstrate altered pituitary-adrenal axis responses to hCRH. This is particularly evident in the sickest patients with the highest degree of inflammatory profile who ultimately do not survive.

More than a disorder of macrocirculation, sepsis is a disease affecting the microcirculation and the tissue metabolism. In vivo microdialysis (MD) is a bedside technique that can monitor tissue metabolic changes. We conducted this study aiming (1) to assess whether patients at different sepsis stages present with different MD-assessed tissue metabolic profiles and (2) to determine if different underlying types of infections and implicated pathogens are associated with dissimilar metabolic alterations. We studied 90 mechanically ventilated patients, 65 with septic shock and 25 with severe sepsis. An MD catheter was inserted in the subcutaneous adipose tissue of the upper thigh and interstitial fluid samples were collected along with arterial blood samples every 4 h for a maximum of 6 days. Lactate, pyruvate, glycerol, and glucose concentrations were measured. During the study period, patients with septic shock had higher MD-assessed glycerol (P = 0.009), glycerol gradient (P = 0.016), and glucose (P = 0.004) than patients with severe sepsis, whereas tissue lactate, lactate gradient, and pyruvate dropped significantly with time (P = 0.007

Objective To define the potential of resistant gram-negative colonization surveillance to predict etiology of subsequent infection and improve adequacy of empiric antimicrobial treatment.

Sir: We read with great interest the recent article by Chinga-Alayo et al. [1] regarding the prognostic significance of hormonal measurements in critically ill patients. This study assessed adrenal and thyroid function but also focused on other hormones, including growth hormone, dehydroepiandrosterone, and prolactin. This is highly important since there is evidence that the latter hormones modulate humoral and cellular immune functions [2, 3]. In this context it is surprising that the authors failed to show differences in growth hormone, dehydroepiandrosterone, or prolactin levels between survivors and nonsurvivors among critically ill patients (Table 2). We would like to present our experience on the topic of hormonal measurements in critically ill patients. We performed blood sampling in 150 severely ill patients within 24 h after ICU admission to investigate whether hormone levels differ between survivors and nonsurvivors. The preliminary analysis of our data revealed no differences between survivors and nonsurvivors in terms of cortisol, corticotropin, free thyroxine, and tri-iodothyronine levels, but survivors had higher concentrations of thyroidstimulating hormone, prolactin, and dehydroepiandrosterone sulfate than nonsurvivors [4]. The reason for the discrepant results with respect to prolactin and dehydroepiandrosterone levels is unclear. Possible explanations include the timing of sampling, the assays used, and more importantly the differences in patient population. Our ICU is a medical and surgical unit admitting a large number of polytraumatized patients, including those with severe traumatic brain injury while the cohort of Chinga-Alayo et al. comprised only a small number of trauma patients (n = 4) and possibly of surgical cases. Nevertheless, the study by Chinga-Alayo and coworkers highlights the importance of measuring hormones in critically ill patients. Endocrine alterations are frequently observed in severely ill patients, they relate to mortality, and of particular importance, as the current study showed, they improve our predictive ability when used in conjunction with well established severity scores. Further research is needed to validate such findings in a larger cohort comprising a wider range of ICU patients. In such a case it might be justified to incorporate a hormonal score to the already available scoring systems. References