Critical Care 2017, 21(Suppl 1):P349 Introduction Imbalance in cellular energetics has been suggested to be an important mechanism for organ failure in sepsis and septic shock. We hypothesized that such energy imbalance would either be caused by metabolic changes leading to decreased energy production or by increased energy consumption. Thus, we set out to investigate if mitochondrial dysfunction or decreased energy consumption alters cellular metabolism in muscle tissue in experimental sepsis. Methods We submitted anesthetized piglets to sepsis (n = 12) or placebo (n = 4) and monitored them for 3 hours. Plasma lactate and markers of organ failure were measured hourly, as was muscle metabolism by microdialysis. Energy consumption was intervened locally by infusing ouabain through one microdialysis catheter to block major energy expenditure of the cells, by inhibiting the major energy consuming enzyme, N+/K + -ATPase. Similarly, energy production was blocked infusing sodium cyanide (NaCN), in a different region, to block the cytochrome oxidase in muscle tissue mitochondria. Results All animals submitted to sepsis fulfilled sepsis criteria as defined in Sepsis-3, whereas no animals in the placebo group did. Muscle glucose decreased during sepsis independently of N+/K + -ATPase or cytochrome oxidase blockade. Muscle lactate did not increase during sepsis in naïve metabolism. However, during cytochrome oxidase blockade, there was an increase in muscle lactate that was further accentuated during sepsis. Muscle pyruvate did not decrease during sepsis in naïve metabolism. During cytochrome oxidase blockade, there was a decrease in muscle pyruvate, independently of sepsis. Lactate to pyruvate ratio increased during sepsis and was further accentuated during cytochrome oxidase blockade. Muscle glycerol increased during sepsis and decreased slightly without sepsis regardless of N+/K + -ATPase or cytochrome oxidase blocking. There were no significant changes in muscle glutamate or urea during sepsis in absence/presence of N+/K + -ATPase or cytochrome oxidase blockade. ConclusionsThese results indicate increased metabolism of energy substrates in muscle tissue in experimental sepsis. Our results do not indicate presence of energy depletion or mitochondrial dysfunction in muscle and should similar physiologic situation be present in other tissues, other mechanisms of organ failure must be considered. , and long-term follow up has shown increased fracture risk [2]. It is unclear if these changes are a consequence of acute critical illness, or reduced activity afterwards. Bone health assessment during critical illness is challenging, and direct bone strength measurement is not possible. We used a rodent sepsis model to test the hypothesis that critical illness causes early reduction in bone strength and changes in bone architecture. Methods 20 Sprague-Dawley rats (350 ± 15.8g) were anesthetised and randomised to receive cecal ligation and puncture (CLP) (50% cecum length, 18G needle single pass through anterior and posterior wa...
BackgroundShock states are characterized by impaired tissue perfusion and microcirculatory alterations, which are directly related to outcome. Skin perfusion can be noninvasively evaluated using skin laser Doppler (SLD), which, when coupled with a local thermal challenge, may provide a measure of microcirculatory reactivity. We hypothesized that this microvascular reactivity would be impaired in patients with circulatory shock and would be a marker of severity.MethodsWe first evaluated skin blood flow (SBF) using SLD on the forearm and on the palm in 18 healthy volunteers to select the site with maximal response. Measurements were taken at 37 °C (baseline) and repeated at 43 °C. The 43 °C/37 °C SBF ratio was calculated as a measure of microvascular reactivity. We then evaluated the SBF in 29 patients with circulatory shock admitted to a 35-bed department of intensive care and in a confirmatory cohort of 35 patients with circulatory shock.ResultsIn the volunteers, baseline SBF was higher in the hand than in the forearm, but the SBF ratio was lower (11.2 [9.4–13.4] vs. 2.0 [1.7–2.6], p < 0.01) so we used the forearm for our patients. Baseline forearm SBF was similar in patients with shock and healthy volunteers, but the SBF ratio was markedly lower in the patients (2.6 [2.0–3.6] vs. 11.2 [9.4–13.4], p < 0.01). Shock survivors had a higher SBF ratio than non-survivors (3.2 [2.2–6.2] vs. 2.3 [1.7–2.8], p < 0.01). These results were confirmed in the second cohort of 35 patients. In multivariable analysis, the APACHE II score and the SBF ratio were independently associated with mortality.ConclusionsMicrocirculatory reactivity is decreased in patients with circulatory shock and has prognostic value. This simple, noninvasive test could help in monitoring the peripheral microcirculation in acutely ill patients.Electronic supplementary materialThe online version of this article (10.1186/s13613-018-0393-7) contains supplementary material, which is available to authorized users.
Infantile hemangiomas (IH) complicated by ulceration, disfigurement, functional impairment or life-threatening conditions need early, safe and effective treatment. This study explores the impact of propranolol on complicated IH. We report our experience of 62 patients treated with oral propranolol for complicated IH. The effect of propranolol was assessed using a score on a visual analogue scale integrated with echo, magnetic resonance or endoscopic findings. The average age at the beginning of the treatment was seven months [standard deviation (SD)±8.9], with a median of four months (range 1-53 months). The average age at the end of the treatment was 15 months (SD±8.4), with a median of 13 months (range 7-59 months). The mean treatment length was eight months (SD±3.2). Oral propranolol was successful in 95.2% of the patients in reducing the volume, the intensity of color and the elevation of IH. Statistically significant improvement of IH volume was observed in the first two months of therapy (P≤0.001), and between the second month and the end of the treatment (P<0.05). No significant bradycardia or hypotension occurred. Severe hypoglycemia occurred in one patient. Mild adverse effects were observed in seven patients. Our study demonstrates that propranolol administered orally at 2 to 3 mg/kg/day has a rapid therapeutic effect leading to remarkable shortening of the natural course of IH and it is safe in the majority of patients.
Invasive fungal infections (IFIs) are an increasing problem in intensive care units (ICUs), and conventional diagnostic methods are not always reliable or timely enough to deliver appropriate antimicrobial therapy. The dosage of fungal antigens in serum is a promising diagnostic technique, but several confounding factors, such as treatment with immunoglobulins (Ig), albumin, or antifungals, could interfere with the correct interpretation of the (1,3)-beta-D-glucan (BG) assay. This study assessed the reliability of the BG assay and the influence of timing and dosage of major confounding factors on circulating levels of IFI biomarkers. 267 ICU patients who underwent a BG assay were retrospectively studied. The timing and dosage of albumin, use of azole treatment, and infusions of intravenous IgG, red blood cells, concentrated platelets, and frozen plasma were analyzed to find possible correlations with the BG results. The sensitivity and specificity of the BG assay were calculated. The BG test in serum showed high sensitivity (82.9 %) but low specificity (56.7 %). The optimal cut-off for the test was 95.9 pg/mL. The mean BG level in proven invasive candidiasis was around 400 pg/mL. The only factor that was found to significantly confound (p < 0.05) the diagnostic performance of the BG assay was the administration of more than 30 g of albumin within 2 days prior to BG testing. The BG assay remains a useful diagnostic test in ICU patients and the levels of BG are useful in evaluating the positive predictive value of this biomarker. The only confounding factor in our study was the use of albumin.
Rapid detection of microorganisms in respiratory specimens is of paramount importance to drive the proper antibiotic regimen to prevent complications and transmission of infections. In the present study, the respiFISH® HAP Gram (-) Panel (miacom diagnostics GmbH, Duesseldorf, Germany) for the etiological diagnosis of hospital-acquired pneumonia was compared with the traditional culture method for the detection of major Gram-negative pathogens in respiratory specimens. respiFISH® combined the classical fluorescence in situ hybridization (FISH) technology with fluorescence-labeled DNA molecular beacons as probes. From September 2011 to January 2012, 165 samples were analyzed: the sensitivity and specificity were 94.39 and 87.93%, respectively. Only six pathogens (3.6%) were not identified with respiFISH®, while seven specimens (3%) provided false-positive results. This beacon-based identification shortens the time to result by at least one work day, providing species-level identification within half an hour. Considering the high sensitivity and specificity and the significant time saving, the introduction of bbFISH® assays could effectively complement traditional systems in microbiology laboratories.
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