Tissue perfusion assesment in shock

Apesar das diversas inovações tecnológicas e do melhor entendimento fisiopatológico dos estados de choque, esta condição permanece com elevada taxa de morbimortalidade. Uma das explicações mais aceitas para a taxa elevada é o desenvolvimento da síndrome de disfunção de múltiplos órgãos (SDMO), secundária à hipoperfusão tecidual persistente. Assim, é evidente a importância da avaliação da perfusão tecidual em tais quadros, bem como possíveis interferências terapêuticas a partir da avaliação. Nesta revisão, são abordadas noções básicas sobre a monitorização clínica e laboratorial da perfusão tecidual no choque, incluindo transporte de O2, consumo e taxa de extração de O2 saturação venosa mista de O2, lactato e gradiente gastroarterial de CO2. Tais dados são fundamentais para a correta interpretação e melhor intervenção terapêutica, visando adequar o desequilíbrio presente entre oferta/consumo de O2 e, desta forma, interromper a série de eventos fisiopatológicos que resulta em SDMO e, em muitas condições, em morte. Nesse contexto, algumas metas devem ser alcançadas durante a ressuscitação de pacientes com síndrome do choque, a saber: pressão arterial média > 65 mmHg; diurese ³ 1 ml/kg/hora; débito cardíaco suficiente para manter uma SvO2 >65%; lactato sérico < 2 mmol/L, destacando que, mesmo quando normalizadas as variáveis sistêmicas de oxigenação, graves distúrbios perfusionais regionais ainda podem existir, sendo necessário recorrer à monitorização regional através da avaliação do pCO2-gap.Although new technologies have emerged and the tissue perfusion assessment has improved, shock remains with a high mortality ratio. Multiple organ dysfunction syndrome (MODS) due to tissue hypoperfusion is the best reason to explain this high mortality ratio in these patients. Hence, tissue perfusion assessment has the pivotal role in the shocked patient evaluation, because some therapeutic interventions can be performed. In this review, will be highlighted the main clinic signs and laboratories findings observed in hypoperfusion syndromes, including oxygen transport, oxygen delivery, oxygen consumption, oxygen extraction ratio, oxygen mixed venous saturation, arterial lactate end gastric-arterial CO2 gradient. These concepts are very important to understand and choose the best intervention for breaking events that are responsible for MODS development and death. The goals of resuscitation are also provided including mean arterial pressure above 65 mm Hg, mixed venous oxygen saturation above 65%, and lactate levels below 2 mMol/L. However, regional hypoperfusion can persist despite of restoring global hemodynamic variables. Hence, gastric-mucosal PCO2 could be a therapy-guide.   &nbsp

Expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and mitochondrial oxidative phosphorylation in septic patients

<div><p>Background and objectives</p><p>Sepsis is a complex disease that is characterized by activation and inhibition of different cell signaling pathways according to the disease stage. Here, we evaluated genes involved in the TLR signaling pathway, oxidative phosphorylation and oxidative metabolism, aiming to assess their interactions and resulting cell functions and pathways that are disturbed in septic patients.</p><p>Materials and methods</p><p>Blood samples were obtained from 16 patients with sepsis secondary to community acquired pneumonia at admission (D0), and after 7 days (D7, N = 10) of therapy. Samples were also collected from 8 healthy volunteers who were matched according to age and gender. Gene expression of 84 genes was performed by real-time polymerase chain reactions. Their expression was considered up- or down-regulated when the fold change was greater than 1.5 compared to the healthy volunteers. A p-value of ≤ 0.05 was considered significant.</p><p>Results</p><p>Twenty-two genes were differently expressed in D0 samples; most of them were down-regulated. When gene expression was analyzed according to the outcomes, higher number of altered genes and a higher intensity in the disturbance was observed in non-survivor than in survivor patients. The canonical pathways altered in D0 samples included interferon and iNOS signaling; the role of JAK1, JAK2 and TYK2 in interferon signaling; mitochondrial dysfunction; and superoxide radical degradation pathways. When analyzed according to outcomes, different pathways were disturbed in surviving and non-surviving patients. Mitochondrial dysfunction, oxidative phosphorylation and superoxide radical degradation pathway were among the most altered in non-surviving patients.</p><p>Conclusion</p><p>Our data show changes in the expression of genes belonging to the interacting TLR cascades, NADPH-oxidase and oxidative phosphorylation. Importantly, distinct patterns are clearly observed in surviving and non-surviving patients. Interferon signaling, marked by changes in JAK-STAT modulation, had prominent changes in both survivors and non-survivors, whereas the redox imbalance (iNOS signaling, oxidative phosphorylation and superoxide radical degradation) affecting mitochondrial functions was prominent in non-surviving patients.</p></div

Volcano plot representing the gene expression changes in admission samples (D0) of septic patients compared to healthy volunteers.

<p>A. all patients; B. survivors; and C. non-survivors. The x axis represents the Log₂ fold change and Y axis—Log₁₀ <i>P</i> value. The cut off for significance is set as the fold change ≥ 1.5 and P value ≤ 0.05. The genes are represented as dots, where the green color represents down regulation, red represents up regulation and gray indicates no significant changes.</p

Demonstration of differential gene expression profile in septic patients in admission (D0) samples using curated pathway functional of IPA.

<p>A. all patients; B. survivors; and C. non-survivors. Gene expression changes with FC ≥ 1.5 and P value ≤ 0.05 were used to generate the interaction network. The intensity of the color represents up-regulation (red), down-regulation (green) or no significant regulation (gray).</p

Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: A randomized controlled trial

Background: Transfusion of blood components prior to invasive procedures in cirrhosis patients is high and associated with adverse events. Objectives: We compared three transfusion strategies prior to central venous catheterization in cirrhosis patients. Patients/Methods: Single center randomized trial that included critically ill cirrhosis patients with indication for central venous line in a tertiary private hospital in Brazil. Interventions: Restrictive protocol, thromboelastometry-guided protocol, or usual care (based on coagulogram). The primary endpoint was the proportion of patients transfused with any blood component (ie, fresh frozen plasma, platelets, or cryoprecipitate). The secondary endpoints included incidence of bleeding and transfusion-related adverse events. Results: A total of 57 patients (19 per group; 64.9% male; mean age, 53.4 ± 11.3 years) were enrolled. Prior to catheterization, 3/19 (15.8%) in the restrictive arm, 13/19 (68.4%) in the thromboelastometry-guided arm, and 14/19 (73.7%) in the coagulogram-guided arm received blood transfusion (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.01-0.45; P =.002 for restrictive versus coagulogram-guided arm; OR, 0.09; 95% CI, 0.01-0.56; P =.006 for restrictive versus thromboelastometry-guided arm; and OR, 0.77; 95% CI, 0.14-4.15; P =.931 for thromboelastometry-guided versus coagulogram-guided arm). The restrictive protocol was cost saving. No difference in bleeding, length of stay, mortality, and transfusion-related adverse events was found. Conclusions: The use of a restrictive strategy is associated with a reduction in transfusion prior to central venous catheterization and costs in critically ill cirrhosis patients. No effect on bleeding was found among the groups