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Introduction Acute heart failure (AHF) is characterized by inadequate cardiac output (CO), congestive symptoms, poor peripheral perfusion and end-organ dysfunction. Treatment often includes a combination of diuretics, oxygen, positive pressure ventilation, inotropes and vasodilators or vasopressors. Lactate is a marker of illness severity but is also an important metabolic substrate for the myocardium at rest and during stress. We tested the effects of half-molar sodium lactate infusion on cardiac performance in AHF. Methods We conducted a prospective, randomised, controlled, open-label, pilot clinical trial in 40 patients fulfilling two of the following three criteria for AHF: (1) left ventricular ejection fraction

Introduction Reversible myocardial depression occurs early in severe sepsis and septic shock. The question of whether or not early ventricular depression or dilatation is associated with lower mortality in these patients remains controversial. Most studies on this topic were small in size and hence lacked statistical power to answer the question. This meta-analysis attempted to answer the question by increasing the sample size via pooling relevant studies together. Methods PubMed, Embase (and Medline) databases and conference abstracts were searched to July 2012 for primary studies using well-defined criteria. Two authors independently screened and selected studies. Eligible studies were appraised using defined criteria. Additional information was sought the corresponding authors if necessary. Study results were pooled using random effects models. Standardized mean differences (SMD) between survivor and non-survivor groups were used as the main effect measures. Results A total of 62 citations were found. Fourteen studies were included in the analysis. The most apparent differences between the studies were sample sizes and exclusion criteria. All studies, except four pre-1992 studies, adopted the Consensus definition of sepsis. Altogether, there were >700 patients available for analysis of the left ventricle and >400 for the right ventricle. There were no significant differences in left ventricular ejection fractions, right ventricular ejection fractions, and right ventricular dimensions between the survivor and non-survivor groups. When indexed against body surface area or body height, the survivors and non-survivors had similar left ventricular dimensions. However, the survivors had larger non-indexed left ventricular dimensions. Conclusion This meta-analysis failed to find any evidence to support the view that the survivors from severe sepsis or septic shock had lower ejection fractions. However, non-indexed left ventricular dimensions were mildly increased in the survivor group but the indexed dimensions were similar between the groups. Both survivors and non-survivors had similar right ventricular dimensions.

T lymphocytes are crucial immune cells. We analysed T-cell subsets phenotypes and tested, on a single cell level, their ability to produce key cytokines in early human sepsis.

Extracellular release of ATP is an important modulator of immune response. ATP plasma concentration is increased in sepsis [1]. IFNγ plays a critical role in host defense by promoting Th1 phenotype and bacterial clearance. Low IFNγ levels are associated with the Th2 phenotype consistent with critical illness anergy [2]. It has been reported that 100 and 300 mM ATP increased LPS/PHA-stimulated IL-10 secretion in human blood [3]. Higher IL-10/IFNγ ratio shifts the immune phenotype from Th1 to Th2 response. We studied the effect of ATP on LPS-stimulated IL-10 and IFNγ secretion in a standardized ex-vivo whole human blood culture.

Tracheostomy is one of the more commonly performed procedures in critically ill patients yet the optimal method of performing tracheostomies in this population remains to be established. The aim of this study was to systematically review and quantitatively synthesize all randomized clinical trials (RCTs), comparing elective percutaneous dilatational tracheostomy (PDT) and surgical tracheostomy (ST) in adult critically ill patients with regards to major short and long term outcomes. MEDLINE, EMBASE, CINAHL and the Cochrane Controlled Clinical Trials Register databases were searched to identify relevant studies. Additionally, bibliographies and selected conference proceedings were reviewed, and experts in the field and manufacturers of two PDT kits were contacted. Randomized clinical trials comparing any method of elective PDT to ST that included critically ill adults and reported at least one clinically relevant outcome were included. Data extracted included trial characteristics, measures of study validity, and clinically relevant outcomes. Seventeen RCTs involving 1,212 patients were included. Most PDTs used a multiple dilator technique and were performed in the intensive care unit (ICU). The pooled odds ratio (OR) for wound infection was 0.28 (95% confidence interval (CI), 0.16 to 0.49, p < 0.0005), indicating a significant reduction with PDT compared to ST. Overall, PDT was equivalent to ST for bleeding, major peri-procedural and long-term complications; however, subgroup analysis suggested PDT resulted in a lower incidence of bleeding (OR = 0.29 (95% CI 0.12 to 0.75, p = 0.01)) and death (OR = 0.71 (95% CI 0.50 to 1.0, p = 0.05)) when the STs were performed in the operating theatre. PDT reduces the overall incidence of wound infection and may further reduce clinical relevant bleeding and mortality when compared with ST performed in the operating theatre. PDT, performed in the ICU, should be considered the procedure of choice for performing elective tracheostomies in critically ill adult patients.

The calcium sensitizer levosimendan is a novel inotrope used for the treatment of cardiac failure. Animal data suggest pulmonary vasodilating properties and levosimendan has been suggested for the treatment of right ventricular (RV) failure despite scarce data in patients [1].

Levosimendan is used intravenously for the management of heart failure. At the therapeutic dose, levosimendan acts predominantly as a calcium sensitizer and ATP-sensitive K+-channel (KATP-channel) opener. It binds directly to the calcium-dependent site on troponin C, stabilizing the calcium-induced conformational change and enhances the calcium sensitivity of the cardiac myofilaments. The advantages of a calcium sensitizer over dobutamine is the lack of intracellular calcium overload and that it acts without increasing the energy demand for handling intracellular calcium.

We studied the medical personnel's power of distinction various types of respirators in CPAP and CPAP+pressure support (PS) modes.

Inhaled nitric oxide (NO) causes selective pulmonary vasodilation. In experiment, pulmonary arteries were shown to be primary site of NO effect. Our aim was to study the effect of inhaled NO on pulmonary vasculature in ARDS patients.

Fluid resuscitation in the critically ill is a hot topic. The current strategy of rapid and adequate resuscitation in shock followed by conservative fluid administration is often difficult to achieve with standard crystalloid solutions. Research into alternative intravenous fluids tailored to individual patient needs is required. In the previous issue of Critical Care, Somasetia and colleagues compare the effects of hypertonic sodium lactate with the World Health Organization-recommended strategy of Ringer’s lactate resuscitation in children with severe Dengue, a viral infection for which causal treatment and vaccination are not available. The results not only suggest unimpaired lactate metabolism during shock in children but document improvement in endothelial barrier function, limited coagulopathy, and avoidance of fluid overload with hypertonic sodium lactate. Their study invites several important questions to be answered. Is hypertonicity or lactate per se important for the beneficial effects? Are the metabolic or anti-inflammatory effects responsible? Is the raised lactate in shock an adaptive response? Should reduction in lactate levels be the goal of resuscitation? These questions may trigger further research into the role of lactate and lactate-based intravenous fluids in resuscitation of the critically ill.

Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. We conducted gene-expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure, such as bacterial pneumonia, and noninfective systemic inflammatory response syndrome. Whole-blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene-expression beadarrays. Differentially expressed genes were determined by linear mixed-model analysis and overrepresented biological pathways determined by using GeneGo MetaCore. The gene-expression profile of H1N1 influenza A pneumonia was distinctly different from those of bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene-expression profile is characterized by upregulation of genes from cell-cycle regulation, apoptosis, and DNA-damage-response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene-expression profile of influenza infection persisted through 5 days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection in whom bacterial co-infection subsequently developed, the influenza gene-expression signature remained unaltered, despite the presence of a superimposed bacterial infection. The whole-blood expression-profiling data indicate that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed the identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly.