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Introduction Adrenal dysfunction may represent critical illness-related corticosteroid insufficiency (CIRCI), as evidenced by a diminished cortisol response to exogenous adrenocorticotropic hormone (ACTH), but this concept and its clinical significance remain highly controversial. We studied the adrenal response to exogenous ACTH as a function of the endogenous cortisol-to-ACTH ratio, a measure of adrenal sensitivity, and of clinical variables, during critical illness and recovery from the acute phase. Methods We prospectively included 59 consecutive septic and nonseptic patients in the intensive care unit with treatment-insensitive hypotension in whom CIRCI was suspected; patients having received etomidate and prolonged corticosteroids were excluded. An ACTH test (250 μg) was performed, followed by a second test after ≥7 days in acute-phase survivors. Serum total and free cortisol, ACTH, and clinical variables were assessed. Patients were divided according to responses (delta, Δ) of cortisol to ACTH at the first and second tests. Results Patients with low (M) Δ cortisol (n = 14 to 17) had higher baseline cortisol and ACTH but lower cortisol/ACTH ratios than patients with a normal Δ cortisol (≥250 nM) in the course of time. A low Δ cortisol in time was associated with more-severe disease, culture-positive sepsis, and prolonged activated prothrombin time. Results for free cortisol were similar. Conclusions Even though the pituitary-adrenal axis is activated after stress during critical illness, diminished adrenal sensitivity to endogenous ACTH predicts a low increase of cortisol to exogenous ACTH, suggesting adrenal dysfunction, irrespective of the stage of disease. The data further suggest a role of disease severity and culture-positive sepsis.

Introduction: Blood transfusion is associated with increased morbidity and mortality in cardiac surgery patients, but cause-and-effect relations remain unknown. We hypothesized that blood transfusion is associated with changes in pulmonary and systemic inflammation and coagulation occurring in patients who do not meet the clinical diagnosis of transfusion-related acute lung injury (TRALI). Methods: We performed a case control study in a mixed medical-surgical intensive care unit of a university hospital in the Netherlands. Cardiac surgery patients (n = 45) were grouped as follows: those who received no transfusion, those who received a restrictive transfusion (one two units of blood) or those who received multiple transfusions (at least five units of blood). Nondirected bronchoalveolar lavage fluid (BALF) and blood were obtained within 3 hours postoperatively. Normal distributed data were analyzed using analysis of variance and Dunnett’s post hoc test. Nonparametric data were analyzed using the Kruskal-Wallis and Mann-Whitney U tests. Results: Restrictive transfusion increased BALF levels of interleukin (IL)-1b and D-dimer compared to nontransfused controls (P < 0.05 for all), and IL-1b levels were further enhanced by multiple transfusions (P

Introduction: Respiratory syncytial virus (RSV) lower respiratory tract disease is characterised by narrowing of the airways resulting in increased airway resistance, air-trapping and respiratory acidosis. These problems might be overcome using helium-oxygen gas mixture. However, the effect of mechanical ventilation with heliox in these patients is unclear. The objective of this prospective cross-over study was to determine the effects of mechanical ventilation with heliox 60/40 versus conventional gas on respiratory system resistance, air-trapping and CO2 removal. Methods: Mechanically ventilated, sedated and paralyzed infants with proven RSV were enrolled within 24 hours after paediatric intensive care unit (PICU)admission. At T = 0, respiratory system mechanics including respiratory system compliance and resistance, and peak expiratory flow rate were measured with the AVEA ventilator. The measurements were repeated at each interval (after 30 minutes of ventilation with heliox, after 30 minutes of ventilation with nitrox and again after 30 minutes of ventilation with heliox). Indices of gas exchange (ventilation and oxygenation index) were calculated at each interval. Air-trapping (defined by relative change in end-expiratory lung volume) was determined by electrical impedance tomography (EIT) at each interval. Results: Thirteen infants were enrolled. In nine, EIT measurements were performed. Mechanical ventilation with heliox significantly decreased respiratory system resistance. This was not accompanied by an improved CO2 elimination, decreased peak expiratory flow rate or decreased end-expiratory lung volume. Importantly, oxygenation remained unaltered throughout the experimental protocol. Conclusions: Respiratory system resistance is significantly decreased by mechanical ventilation with heliox (ISCRTN98152468). © 2009 Kneyber et al.; licensee BioMed Central Ltd.

Introduction The relationship between isolated traumatic brain injury (TBI) associated coagulopathy and patient prognosis frequently lacks information regarding the time course of coagulation disorders throughout the post-traumatic period. This study was conducted to assess the prevalence and time course of post-traumatic coagulopathy in patients with isolated TBI and the relationship of these hemostatic disorders with outcome. Methods The local Human Subjects Committee approved the study. We retrospectively studied the medical records of computed tomography (CT)-confirmed isolated TBI patients with an extracranial abbreviated injury scale (AIS) 40 seconds and/or a PTT in International Normalized Ratio (INR) >1.2 and/or a platelet count

Introduction Disturbed alveolar fibrin turnover is a cardinal feature of severe pneumonia. Clinical studies suggest that natural inhibitors of coagulation exert lung-protective effects via anticoagulant and possibly also anti-inflammatory pathways. Intravenous infusion of the natural anticoagulants increases the risk of bleeding. Local administration may allow for higher treatment dosages and increased local efficacy while at the same time reducing the risk of bleeding. We evaluated the effect of nebulized anticoagulants on pulmonary coagulopathy and inflammation in a rat model of Streptococcus pneumoniae pneumonia. Methods In this randomized controlled in vivo laboratory study rats were challenged intratracheally with S. pneumoniae, inducing pneumonia, and randomized to treatment with normal saline (placebo), recombinant human activated protein C (rh-APC), plasma-derived antithrombin (AT), heparin or danaparoid, by means of nebulization. Results S. pneumoniae infection increased pulmonary levels of thrombin-antithrombin complexes and fibrin degradation products. All nebulized anticoagulants significantly limited pulmonary coagulopathy. None of the agents except danaparoid resulted in changes in systemic coagulopathy. Treatment with plasma-derived AT reduced outgrowth of S. pneumoniae and histopathologic damage in lungs. In vitro experiments confirmed outgrowth was reduced in bronchoalveolar lavage fluid (BALF) from rats treated with plasma-derived AT compared with placebo. Neutralizing of cationic components in BALF diminished the inhibitory effects on bacterial outgrowth of BALF, suggesting a role for cationic antimicrobial proteins. Conclusions Nebulization of anticoagulants attenuates pulmonary coagulopathy during S. pneumoniae pneumonia in rats while only danaparoid affects systemic coagulation. Nebulized plasma-derived AT reduces bacterial outgrowth and exerts significant lung-protective effects.

Central venous catheters are frequently inserted for various indications. Insertion of a central venous catheter is not without risk; complications occur in more than 15% of the patients. Arterial puncture, hematoma, pneumothorax and hematothorax are among the most well-known and frequently reported complications. In this report, we present a remarkable case of acute diffuse edematous swelling of the thyroid gland as an unexpected and rare complication after attempted subclavian vein catheterization. Acute thyroid swelling rarely occurs after fine needle aspiration, and to our knowledge, we are the first to describe acute thyroid swelling after central venous catheter insertion.

The evidence that severe acute pancreatitis can result in critical illness-related corticosteroid insufficiency following impaired adrenal secretion is accumulating. The study by Peng and coworkers in Critical Care certainly contributes to that idea, even though the question whether relative adrenal insufficiency should prompt for treatment by substitution doses of corticosteroids remains unresolved. The study is discussed in terms of the risk factors, circumstances and significance of impaired corticosteroid secretion by adrenals in severe acute pancreatitis.

There are few data related to the effects of different sources of infection on outcome. We used the Sepsis Occurrence in Acutely ill Patients (SOAP) database to investigate differences in the impact of respiratory tract and abdominal sites of infection on organ failure and survival., Comparative Study, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, SCOPUS: ar.j, info:eu-repo/semantics/published

INTRODUCTION: Optimal nutrition for intensive care patients has been proposed to be the provision of energy as determined by indirect calorimetry, and protein provision of at least 1.2 grams/kg pre-admission weight per day. The evidence supporting these nutritional goals is based on surrogate outcomes and is not yet substantiated by patient oriented, clinically meaningful endpoints. In the present study we evaluated the effects of achieving optimal nutrition in intensive care unit (ICU) patients during their period of mechanical ventilation on mortality. METHODS: Prospective observational cohort study in a mixed medical-surgical, 28-bed intensive care unit in an academic hospital. 243 sequential mixed medical-surgical patients were enrolled on day 3 to 5 after admission if they had an expected stay of at least another 5 to 7 days. They underwent indirect calorimetry as part of routine care. Nutrition was guided by the result of indirect calorimetry and we aimed to provide at least 1.2 grams of protein/kg/day. Cumulative balances were calculated for the period of mechanical ventilation. Outcome parameters were ICU, 28-day and hospital mortality. RESULTS: In women, when corrected for weight, height, Apache II score, diagnosis category, and hyperglycaemic index, patients who reached their nutritional goals compared to those who did not, showed a hazard ratio (HR) of 0.199 for ICU mortality (confidence interval [CI] 0.048 - 0.831; P = 0.027), a HR of 0.079 for 28 day mortality (CI 0.013 - 0.467; P = 0.005) and a HR of 0.328 for hospital mortality (CI 0.113 - 0.952; P = 0.04). Achievement of energy goals whilst not reaching protein goals, did not affect ICU mortality; the HR for 28-day mortality was 0.120 (CI 0.027 - 0.528; P = 0.005) and 0.318 for hospital mortality (CI 0.107 - 0.945; P=0.039). No difference in outcome related to optimal feeding was found for men. CONCLUSIONS: Optimal nutritional therapy improves ICU, 28-day and hospital survival in female ICU patients. Female patients reaching both energy and protein goals have better outcomes than those reaching only the energy goal. In the present study men did not benefit from optimal nutrition

Introduction: Inflammation and coagulation are closely linked, and both can be triggered by endotoxin. Thrombelastometry and impedance aggregometry are of diagnostic and predictive value in critically ill patients. In this observational study we investigated the correlation of endotoxin activity with thrombelasometric and aggregometric variables in patients with systemic inflammation.Methods: Based on a daily screening on a tertiary academic surgical ICU, patients, as soon as they fulfilled two or more criteria for systemic inflammatory response syndrome (SIRS), were included. In whole blood we performed endotoxin activity (EA) assay, thrombelastometry (ROTEM®) and impendance aggregometry (Multiplate®).Results: In total, 49 patients were included with a broad spread of EA levels of (median (minimum to maximum)) 0.27 (0.01 to 0.72), allowing expedient correlative analysis. Clot formation time (CFT) (263 s (60 to 1,438 s)) and clotting time (CT) (1,008 s (53 to 1,481 s)) showed a significant negative correlation with EA level (r = -0.38 (P < 0.005) and r = -0.29 (P < 0.05)). Positive correlations were found for alpha-angle (50° (17 to 78°), r = 0.40 (P < 0.005)) and maximum clot firmness (MCF) (55 mm (5/76), r = 0.27 (P < 0.05)). No significant correlations were found between Lysis Index at 60 minutes (LI60) and EA levels. There was no correlation between EA level and aggregometric values, or classical coagulation parameters.Conclusions: In patients with systemic inflammation, increasing endotoxin concentrations correlate with increased clot formation.