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PURPOSE: The aim of this study was to investigate the impact of acute Paco(2) temporal variation on the standard base excess (SBE) value in critically ill patients. METHODS: A total of 265 patients were prospectively observed; 158 were allocated to the modeling group, and 107 were allocated to the validation group. Two models were developed in the modeling group (one including and one excluding Paco(2) as a variable determinant of SBE), and both were tested in the validation group. RESULTS: In the modeling group, the mathematical model including SIDai, SIG, l-lactate, albumin, phosphate, and Paco(2) had a predictive superiority in comparison with the model without Paco(2) (R(2) = 0.978 and 0.916, respectively). In the validation group, the results were confirmed with significant F change statistics (R(2) change = 0.059, P < .001) between the model with and without Paco(2). A high correlation (R = 0.99, P < .001) and agreement (bias = -0.25 mEq/L, limits of agreement 95% = -0.72 to 0.22 mEq/L) were found between the model-predicted SBE value and the SBE calculated using the Van Slyke equation. CONCLUSIONS: Acute Paco(2) temporal variation is related to SBE changes in critically ill patients.Copyright © 2009 by Elsevier Inc. [ABSTRACT FROM AUTHOR]

Introduction: There is a complex interplay between changes in acid-base components and inflammation. This manuscript aims to explore associations between plasma cytokines and chemokines and acid-base status on admission to intensive care., Methods: We conducted a prospective cohort study in a 13-bed ICU in a tertiary-care center in Brazil. 87 unselected patients admitted to the ICU during a 2-year period were included. We measured multiple inflammatory mediators in plasma using multiplex assays and evaluated the association between mediator concentrations and acid-base variables using a variety of statistical modeling approaches, including generalized linear models, multiadaptive regression splines and principal component analysis., Results: We found a positive association between strong ion gap (SIG) and plasma concentrations of interleukin (IL)6, 8, 10 and tumor necrosis factor (TNF); whereas albumin was negatively associated with IL6, IL7, IL8, IL10, TNF and interferon (IFN)α. Apparent strong ion difference (SIDa) was negatively associated with IL10 and IL17. A principal component analysis including SAPS 3 indicated that the association between acid-base components and inflammatory status was largely independent of illness severity, with both increased SIG and decreased SIDa (both drivers of acidosis) associated with increased inflammation., Conclusion: Acid-base variables (especially increased SIG, decreased albumin and decreased SIDa) on admission to ICU are associated with immunological activation. These findings should encourage new research into the effects of acid-base status on inflammation.

Objective: To analyze the cost-utility of using extracorporeal oxygenation for patients with severe acute respiratory distress syndrome in Brazil., Methods: A decision tree was constructed using databases from previously published studies. Costs were taken from the average price paid by the Brazilian Unified Health System (Sistema Único de Saúde; SUS) over three months in 2011. Using the data of 10,000,000 simulated patients with predetermined outcomes and costs, an analysis was performed of the ratio between cost increase and years of life gained, adjusted for quality (cost-utility), with survival rates of 40 and 60% for patients using extracorporeal membrane oxygenation., Results: The decision tree resulted in 16 outcomes with different life support techniques. With survival rates of 40 and 60%, respectively, the increased costs were R$=-301.00/-14.00, with a cost of R$=-30,913.00/-1,752.00 paid per six-month quality-adjusted life-year gained and R$=-2,386.00/-90.00 per quality-adjusted life-year gained until the end of life, when all patients with severe ARDS were analyzed. Analyzing only patients with severe hypoxemia (i.e., a ratio of partial oxygen pressure in the blood to the fraction of inspired oxygen <100 mmHg), the increased cost was R$=-5,714.00/272.00, with a cost per six-month quality-adjusted life-year gained of R$=-9,521.00/293.00 and a cost of R$=-280.00/7.00 per quality-adjusted life-year gained., Conclusion: The cost-utility ratio associated with the use of extracorporeal membrane oxygenation in Brazil is potentially acceptable according to this hypothetical study.

Neuropeptides are an extremely conserved arm of neurobiology. Despite their effects as neurohormones and neurotransmitters, a multitude of other effects have been described, putting in evidence their importance as regulators of immune responses, such as chemotaxis, oxidative burst, pro-inflammatory signaling, and many others. The effects of neuropeptides in the pathophysiology of sepsis, however, remain poorly investigated. A prospective cohort study to investigate the effects of neuropeptides in sepsis was carried out. Here, we describe that neuropeptides are downregulated during septic shock. We propose that it may be a protective mechanism of the host to avoid further inflammatory injury.

Objective: The HLA haplotype has been associated with many autoimmune diseases, but no associations have been described in sepsis. This study aims to investigate the HLA system as a possible marker of genetic sepsis susceptibility., Methods: This is a prospective cohort study including patients admitted to an intensive care unit and healthy controls from a list of renal transplant donors. Patients with less 18 years of age; pregnant or HIV positive patients; those with metastatic malignancies or receiving chemotherapy; or with advanced liver disease; or with end-of-life conditions were excluded. The DNA was extracted from the whole blood and HLA haplotypes determined using MiliPlex® technology., Results: From October 2010 to October 2012, 1,121 patients were included (1,078 kidney donors, 20 patients admitted with severe sepsis and 23 with septic shock). HLA-A*31 positive subjects had increased risk of developing sepsis (OR 2.36, 95%CI 1.26-5.35). Considering a p value <0.01, no other significant association was identified., Conclusion: HLA-A*31 expression is associated to risk of developing sepsis.

Objective: Corrected anion gap and strong ion gap are commonly used to estimate unmeasured anions. We evaluated the performance of the anion gap corrected for albumin, phosphate and lactate in predicting strong ion gap in a mixed population of critically ill patients. We hypothesized that anion gap corrected for albumin, phosphate and lactate would be a good predictor of strong ion gap, independent of the presence of metabolic acidosis. In addition, we evaluated the impact of strong ion gap at admission on hospital mortality., Methods: We included 84 critically ill patients. Correlation and agreement between the anion gap corrected for albumin, phosphate and lactate and strong ion gap was evaluated by the Pearson correlation test, linear regression, a Bland-Altman plot and calculating interclass correlation coefficient. Two subgroup analyses were performed: one in patients with base-excess <-2 mEq/L (low BE group - lBE) and the other in patients with base-excess >-2 mEq/L (high BE group - hBE). A logistic regression was performed to evaluate the association between admission strong ion gap levels and hospital mortality., Results: There was a very strong correlation and a good agreement between anion gap corrected for albumin, phosphate and lactate and strong ion gap in the general population (r2=0.94; bias 1.40; limits of agreement -0.75 to 3.57). Correlation was also high in the lBE group (r2=0.94) and in the hBE group (r2=0.92). High levels of strong ion gap were present in 66% of the whole population and 42% of the cases in the hBE group. Strong ion gap was not associated with hospital mortality by logistic regression., Conclusion: Anion gap corrected for albumin, phosphate and lactate and strong ion gap have an excellent correlation. Unmeasured anions are frequently elevated in critically ill patients with normal base-excess. However, there was no association between unmeasured anions and hospital mortality.

Background: Septic shock is the first cause of death in Intensive Care Units. Despite experimental data showing increased inflammatory response of aged animals following infection, the current accepted hypothesis claims that aged patients are immunocompromised, when compared to young individuals., Results: Here, we describe a prospective cohort study designed to analyze the immune profile of this population., Conclusion: Older people are as immunocompetent as the young individual, regarding the cytokines, chemokines and growth factors response to devastating infection.

Introduction: Hypocalcemia is a common and poorly understood finding in critically ill patients. The current study was designed to assess the association of ionized calcium, vitamin D, phosphorus and Parathyroid hormone levels in a cohort of patients with and without kidney dysfunction admitted for sepsis or non-infectious causes., Methods: Prospective cohort clinical and biochemical study., Results: We confirmed that hypocalcemia and hypovitaminosis D are a common finding in critically ill patients. Parathyroid hormone levels significantly rise in septic shock. In the recovery phase, however, despite persistent hypocalcemia, Parathyroid hormone levels abruptly decrease in patients with kidney dysfunction, but not in patients with normal renal function., Conclusions: The systemic inflammatory response syndrome probably leads to inappropriately high Parathyroid hormone levels during septic shock. In the recovery phase, Parathyroid hormone levels decrease, but calcium levels remain low, displaying evidence that the parathyroid is not responding as expected. Since Parathyroid hormone receptors and calcium-sensing receptors have been described in immune cells and other cell types, we propose that these effects may have a plethora of other deleterious effects, with important implications to the pathogenesis of septic shock.

C-reactive protein (CRP) is an acute-phase protein whose requests have been growing exponentially in several countries, including Brazil. In this study, the use of CRP in several clinical situations was reviewed by a group of physicians comprised by specialists in internal medicine, medical emergencies, intensive care, screening, and laboratory medicine, aiming to analyze the applicable literature and to propose guidelines for a more rational use of this laboratory test. The result was the creation of flowcharts guiding CRP request, adjusted to four different healthcare environments, namely, intensive care units, emergency room, wards, and outpatient clinics. These flowcharts, as well as a more detailed discussion on several clinical recommendations for the test, are presented in this study.

Sepsis is a complex clinical situation responsible for thousands of deaths annually in intensive care units around the globe. Despite all our progress in providing medical care to critically ill patients, mortality of severe forms of sepsis did not decrease as expected. Part of this phenomenon is due to our defective understanding about the host immune response to aggression by a microorganism, including the part played by the pattern-recognition receptors (PRRs) in this process. PRRs are part of the innate immunity responsible for detecting non-self antigens and trigger the initial inflammatory response. The best known PRRs are the tol-like receptors (TLRs). In this article, we review some of our knowledge regarding the role of TLRs in sepsis, both in experimental models and in human patients. The improvement in our knowledge about the mediators and signaling pathways that control this immune response is crucial for the development of better markers of disease and new therapeutic targets, leading us to improve the way we treat septic patients.

The aims of this study were to determine whether standard base excess (SBE) is a useful diagnostic tool for metabolic acidosis, whether metabolic acidosis is clinically relevant in daily evaluation of critically ill patients, and to identify the most robust acid-base determinants of SBE. Thirty-one critically ill patients were enrolled. Arterial blood samples were drawn at admission and 24 h later. SBE, as calculated by Van Slyke's (SBE VS) or Wooten's (SBE W) equations, accurately diagnosed metabolic acidosis (AUC = 0.867, 95%CI = 0.690-1.043 and AUC = 0.817, 95%CI = 0.634-0.999, respectively). SBE VS was weakly correlated with total SOFA (r = -0.454, P < 0.001) and was similar to SBE W (r = -0.482, P < 0.001). All acid-base variables were categorized as SBE VS <-2 mEq/L or SBE VS <-5 mEq/L. SBE VS <-2 mEq/L was better able to identify strong ion gap acidosis than SBE VS <-5 mEq/L; there were no significant differences regarding other variables. To demonstrate unmeasured anions, anion gap (AG) corrected for albumin (AG A) was superior to AG corrected for albumin and phosphate (AG A+P) when strong ion gap was used as the standard method. Mathematical modeling showed that albumin level, apparent strong ion difference, AG A, and lactate concentration explained SBE VS variations with an R(2) = 0.954. SBE VS with a cut-off value of <-2 mEq/L was the best tool to diagnose clinically relevant metabolic acidosis. To analyze the components of SBE VS shifts at the bedside, AG A, apparent strong ion difference, albumin level, and lactate concentration are easily measurable variables that best represent the partitioning of acid-base derangements.

Background and Objectives: The amount of metabolic acidosis measured through the standard base excess (SBE) has been shown to be an outcome marker and its improvement has been associated with better survival. We studied the mechanism of standard base excess variation in the first three days of intensive care unit (ICU) stay through the evaluation of independent variables of physico-chemical approach., Methods: Data were retrieved from our prospective collected data base from patients with diagnosis of septic shock, daily up to the third day after the ICU admission. Single correlations between SBE and independent variables were performed as well as a mathematical multilinear model was built to disclose the SBE variation determinants., Results: We have shown that in septic shock patients the standard base excess variation during the first three days of ICU stay is weakly correlated to strong ion gap (SIG), lactate, creatinin and PaCO2 when individually analyzed. Analyzing concomitantly those independent variables, we built a mathematical model with a stepwise multilinear regression composed by apparent strong ion difference (SIDa), SIG, PaCO2, albumin and diuresis that resulted in a R² coefficient of 0.866 to determine SBE variation., Conclusions: Variations of metabolic acidosis measured through the standard base excess in septic shock patients when analyzed until the third day after intensive care unit admission, is resultant of interaction of several independent determinants as PaCO2, diuresis, SIG, SIDa and albumin.

Purpose: To compare the evolution of standard base excess and serum lactate level between surviving and non surviving patients with severe sepsis and septic shock resuscitated with early goal-directed therapy., Methods: This is a retrospective study in an intensive care unit of a university tertiary hospital where 65 consecutive severe sepsis and septic shock patients were observed without any intervention in the treatment by the authors of this report., Results: In our study, the mortality of severe sepsis and septic shock patients was 38%. The central venous oxygen saturation of both groups was above 70% after the resuscitative period, excluding the second day of the non survivors group (69.8%). After the second day, the central venous oxygen saturation was significantly higher in the survivors group (P < .001). Standard base excess was initially low in both groups, but from the second day on, the correction of standard base excess was significantly more successful and linear in the survivor group (P < .001). Lactate levels were similar during the evolution of both groups., Conclusions: Although evolutive standard base excess and serum lactate level are still outcome markers in severe sepsis and septic shock patients resuscitated with early goal-directed therapy, other studies must be performed to clarify if hemodynamic interventions based on standard base excess and serum lactate level could be reliable to improve clinical outcomes in severe sepsis and septic shock patients.