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Several prognostic indices have been employed to predict the outcome of surgical critically ill patients. Among them, acute physiology and chronic health evaluation (APACHE) II, sequential organ failure assessment (SOFA) and simplified acute physiology score (SAPS 3) are widely used. It seems that biological markers such as C-reactive protein (CRP), albumin, and blood lactate levels correlate with the degree of inflammation during the immediate postoperative phase and could be used as independent predictors. The objective of this study is to compare the different predictive values of prognostic indices and biological markers in the outcome of 847 surgical patients admitted to the intensive care unit (ICU) in the postoperative phase.The patients were divided into survivors (n = 765, 57.4% males, age 61, interquartile range 51-71) and nonsurvivors (n = 82, 57.3% males, age 70, interquartile range 58-79). APACHE II, APACHE II death probability (DP), SOFA, SAPS 3, SAPS 3 DP, CRP, albumin, and lactate were recorded on ICU admission (first 24 hours). The area under the ROC curve (AUROC) and 95% confidence interval (95% CI) were used to measure the index accuracy to predict mortality.The AUROC and 95% CI for APACHE II, APACHE II DP, SOFA, SAPS 3, SAPS 3 DP, CRP/albumin ratio, CRP, albumin, and lactate were 0.850 (0.824-0.873), 0.855 (0.829-0.878), 0.791 (0.762-0.818), 0.840 (0.813-0.864), 0.840 (0.813-0.864), 0.731 (0.700-0.761), 0.708 (0.676-0.739), 0.697 (0.665-0.728), and 0.601 (0.567-0.634), respectively. The ICU and overall in-hospital mortality were 6.6 and 9.7%, respectively. The APACHE II, APACHE II DP, SAPS 3, SAPS 3 DP, and SOFA scores showed a better performance than CRP/albumin ratio, CRP, albumin, or lactate to predict in-hospital mortality of surgical critically ill patients.Even though all indices were able to discriminate septic from nonseptic patients, only APACHE II, APACHE II DP, SOFA and to a lesser extent SAPS 3, SAPS 3 DP, and blood lactate levels could predict in the first 24-hour ICU admission surgical patients who have survived sepsis.

Background Septic shock is one of the main causes of mortality in intensive care units worldwide. Nutritional support can affect the survival of patients with sepsis. Objective To evaluate whether resting energy expenditure, respiratory quotient, and oxygen consumption and carbon dioxide production (measured by indirect calorimetry) differ between critically ill patients with vs without sepsis. Methods A total of 205 patients receiving mechanical ventilation were evaluated consecutively within the first 48 hours of admission. Demographic and clinical data were collected, including age, body mass index, oxygen consumption, carbon dioxide production, respiratory quotient, and resting energy expenditure, with the clinical data measured or estimated via indirect calorimetry. Results Of the 205 patients, 114 (56%) had no sepsis and 91 (44%) had sepsis. The median values of the studied variables in the no sepsis and sepsis groups, respectively, were as follows: age, 53 vs 58 years (P = .07); body mass index, 25 vs 26 (P = .14); Acute Physiology and Chronic Health Evaluation II score, 24 vs 25 (P = .04); death risk, 47% vs 63% (P = .04); oxygen consumption, 211 vs 202 mL/min (P = .72); and resting energy expenditure, 1434 vs 1430 kcal/d (P = .73). Analysis of receiver operating characteristic curves showed no significant differences between patients with and without sepsis for any of the indirect calorimetry variables. Conclusion In clinical practice, patients with sepsis do not seem to require an increased energy supply. Additional studies are needed to confirm this conclusion.

Introduction Septic shock is a potentially fatal organ dysfunction caused by an imbalance of the host response to infection. The changes in microcirculation during sepsis can be explained by the alterations in the endothelial barrier function. Endothelial progenitor cells (EPCs) are a potential recovery index of endothelial function and it an increase in response to neuromuscular electrical stimulation (NMES) was demonstrated. Therefore, the objective of this study is to investigate the effects of NMES in patients with septic shock. Methods and analysis It is a study protocol for a randomized cross-over design in an intensive care unit of a tertiary University hospital. Thirty-one patients aged 18 to 65 years. The study will be divided in 2 phases: the phase one will be held in the first 72 hours of septic shock and the phase two after 3 days of first assessment. Patients will be randomly selected to the intervention protocol (decubitus position with the limbs raised and NMES) and control protocol (decubitus position with the limbs raised without NMES). After this procedure, the patients will be allocated in group 1 (intervention and control protocol) or group 2 (control and intervention protocol) with a wash-out period of 4 to 6 hours between them. The main outcome is mobilization of EPCs. The secondary outcome is metabolic and hemodynamic data. A linear mixed model will be used for analysis of dependent variables and estimated values of the mean of the differences of each effect.

Background Sepsis is associated with morbidity and mortality, which implies high costs to the global health system. Metabolic alterations that increase glycaemia and glycaemic variability occur during sepsis. Objective To verify mean body glucose levels and glycaemic variability in Intensive Care Unit (ICU) patients with severe sepsis or septic shock. Method Retrospective and exploratory study that involved collection of patients’ sociodemographic and clinical data and calculation of severity scores. Glycaemia measurements helped to determine glycaemic variability through standard deviation and mean amplitude of glycaemic excursions. Results Analysis of 116 medical charts and 6730 glycaemia measurements revealed that the majority of patients were male and aged over 60 years. Surgical treatment was the main reason for ICU admission. High blood pressure and diabetes mellitus were the most usual comorbidities. Patients that died during the ICU stay presented the highest SOFA scores and mean glycaemia; they also experienced more hypoglycaemia events. Patients with diabetes had higher mean glycaemia, evaluated through standard deviation and mean amplitude of glycaemia excursions. Conclusion Organic impairment at ICU admission may underlie glycaemic variability and lead to a less favourable outcome. High glycaemic variability in patients with diabetes indicates that monitoring of these individuals is crucial to ensure better outcomes.

Sepsis is defined as a systemic inflammatory response to infection, which in its severe form is associated with multiple organ dysfunction syndrome (MODS). The precise mechanisms by which MODS develops remain unclear. Neutrophils have a pivotal role in the defense against infections; however, overwhelming activation of neutrophils is known to elicit tissue damage.We investigated the role of the chemokine receptor CCR2 in driving neutrophil infiltration and eliciting tissue damage in remote organs during sepsis.Sepsis was induced in wild-type mice treated with CCR2 antagonist (RS504393) or CCR2(-/-) mice by cecal ligation and puncture (CLP) model. Neutrophil infiltration into the organs was measured by myeloperoxidase activity and fluorescence-activated cell sorter. CCR2 expression and chemotaxis were determined in neutrophils stimulated with Toll-like receptor agonists or isolated from septic mice and patients.CCR2 expression and responsiveness to its ligands was induced in circulating neutrophils during CLP-induced sepsis by a mechanism dependent on Toll-like receptor/nuclear factor-κB pathway. Genetic or pharmacologic inhibition of CCR2 protected mice from CLP-induced mortality. This protection was associated with lower infiltration of neutrophils into the lungs, heart, and kidneys and reduced serum biochemical indicators of organ injury and dysfunction. Importantly, neutrophils from septic patients express high levels of CCR2, and the severity of patient illness correlated positively with increasing neutrophil chemotaxis to CCR2 ligands.Collectively, these data identify CCR2 as a key receptor that drives the inappropriate infiltration of neutrophils into remote organs during sepsis. Therefore, CCR2 blockade is a novel potential therapeutic target for treatment of sepsis-induced MODS.

PURPOSE: The purpose of this study is to compare the resting energy expenditure (REE) obtained by indirect calorimetry (IC) to the REE calculated by predictive equations (Brandi and Liggett) using the oxygen consumption (VO2) obtained by Fick's method in septic patients. METHODS: Prospective study in septic patients admitted in an intensive care unit of a university hospital. Fifteen adult patients (11 men and four women) were studied. VO2 measurements were made using a portable metabolic cart connected to a respirator and a pulmonary artery catheter. RESULTS: The APACHE II at admission was 22.6±7.2 with a mortality risk of 46.1±27.7%. The mean REE obtained by IC and by the Brandi and Liggett equations were 1699±271, 1815±355 and 1361±277 kcal.day-1 respectively. There were no statistically significant differences between the two methods, with the two means showing a difference of 8.7%. REE values were close for IC x BRANDI (r=0.80), but the IC x LIGGETT correlation was only 0.58. CONCLUSIONS: The results suggest that REE can be easily calculated by obtaining VO2 with the Swan-Ganz catheter and using the Brandi equation even for septic patients under mechanical ventilation.OBJETIVO: O objetivo desse estudo foi o de comparar o consumo de oxigênio em repouso (COR) obtido por calorimetria indireta (CI) com valores do COR calculados por equações preditivas (Brandi e Ligget) que utilizam o consumo de oxigênio (VO2) obtido pelo método de Fick em pacientes sépticos. MÉTODOS. Estudo prospectivo em pacientes sépticos internados em unidade de terapia intensiva de um hospital universitário. Quinze pacientes adultos (onze homens e quatro mulheres). As medidas de VO2 foram realizadas usando um aparelho metabólico portátil conectado ao respirador e por cateter em artéria pulmonar. RESULTADOS: O índice APACHE II na admissão foi 22.6±7.2 com risco de mortalidade de 46.1±27.7%. As médias do COR obtidas por CI e pelas equações de Brandi and Liggett foram, respectivamente, 1699±271, 1815±355 e 1361±277 kcal.day-1 Não se observaram diferenças estatisticamente significantes entre os dois métodos com as duas médias mostrando uma diferenças de 8.7%. Os valores de COR Também foram próximo dos valores de CI x BRANDI (r=0.80), mas a correlação com CI x LIGGETT apenas 0.58. CONCLUSÕES: Os resultados sugerem que o COR pode ser facilmente calculado para obter-se o VO2 com o cateter de Swan-Ganz e pelo uso da equação de Brandi para pacientes sépticos em ventilação mecânica.

OBJETIVO: Correlacionar o índice de consumo de oxigênio medido através da calorimetria indireta (VO2I DELTA) às medidas calculadas pela equação reversa de Fick (VO2I FICK) em pacientes graves, vítimas de trauma ou sepse. MÉTODOS: Analisados 14 pacientes vítimas de trauma (n=5) ou sepse (n=9), com média de idade de 39,4 ± 5,4 anos, sendo 10 homens e 4 mulheres, APACHE II de 21,3±1,8, ISS de 24,8±6, Sepsis Score de 19,6±2,3, com risco de óbito calculado pelo APACHE II de 41,9±7,1%, submetidos à ventilação mecânica e monitorização hemodinâmica invasiva com cateter de Swan-Ganz e realizadas, pelos dois métodos, 4 séries de medidas do VO2I (T1 a T4). RESULTADOS: Houve uma boa correlação entre os dois métodos (r = 0,77), para a média das quatro medidas seriadas. Não houve diferença estatisticamente significativa entre os dois métodos nos tempos T1 (VO2I DELTA = 138±28 e VO2I FICK = 159±38 mL.min-1.m-2, p = 0,10) e T3 (VO2I DELTA = 144±26 e VO2I FICK = 158±35 mL.min-1.m-2, p = 0,14). Houve diferença significativa nos tempos T2 (VO2I DELTA = 141±27 e VO2I FICK = 155±26 mL.min-1.m-2, p = 0,03) e T4 (VO2I DELTA = 145±24 e VO2I FICK = 162±26 mL.min-1.m-2, p = 0,01). CONCLUSÃO: A calorimetria indireta é um método não invasivo, isento de complicações, que pode ser usado para avaliação do consumo de oxigênio no paciente grave de forma tão eficaz quanto à equação reversa de Fick.OBJECTIVE: To compare the oxygen consumption index measured by using indirect calorimetry (VO2I Delta) with a portable metabolic cart and calculated according to Fick's principle (VO2 I Fick) in critically ill patients. METHODS: Fourteen patients (10 men and 4 women, mean age 39.4 ± 5.4 years) were analyzed, 5 of them trauma victims and 9 sepsis victims. The following mean scores were obtained for these patients: APACHE II = 21.3±1.8, ISS = 24.8±6, and sepsis score = 19.6±2.3. The mortality risk (odds ratio), calculated from APACHE II, was 41.9±7.1%. All patients underwent mechanical ventilation and invasive hemodynamic monitoring with a Swan-Ganz catheter. VO2 was obtained using the 2 methods (VO2I Delta and VO2I Fick) at 4 different times (T1-T4). RESULTS: A good correlation was found between the 2 methods (r=0.77) for the mean of the 4 serial measurements. No statistically significant differences were observed between indirect calorimetry and Fick's equation at T1 (VO2I Delta = 138±28 and VO2I Fick = 59±38 mL.min-2.m-2, P=0.10) and T3 (VO2I Delta = 144±26 and VO2I Fick = 158±35 mL.min-2.m-2, P=0.14), but a significant difference was observed at T2 (VO2I Delta = 141±27 and VO2I Fick = 155±26 mL.min-2.m-2, P=0.03) and T4 (VO2I Delta = 145±24 and VO2I Fick = 162±26 mL.min-2.m-2, P=0.01). CONCLUSION: We may state that indirect calorimetry can be used for oxygen consumption analysis in critically ill patients and is as efficient as Fick's reverse equation, with the benefit of being a noninvasive and risk-free procedure.

Invasive infection and extraintestinal complications are rarely caused by Plesiomonas shigelloides, a waterborne bacterium belonging to the Vibrionaceae family. We report a case of a 16-year-old female patient with sickle beta-zero thalassemia who survived septic shock caused by P. shigelloides associated with secondary acute respiratory distress syndrome and disseminated intravascular coagulation. Treatment with a carbapenem was successful, and the patient recovered without any sequelae. The previous reports of P. shigelloides sepsis are cited, and possible pathogenic mechanisms are discussed.

PURPOSE: The purpose of this study is to compare the resting energy expenditure (REE) obtained by indirect calorimetry (IC) to the REE calculated by predictive equations (Brandi and Liggett) using the oxygen consumption (VO2) obtained by Fick's method in septic patients. METHODS: Prospective study in septic patients admitted in an intensive care unit of a university hospital. Fifteen adult patients (11 men and four women) were studied. VO2 measurements were made using a portable metabolic cart connected to a respirator and a pulmonary artery catheter. RESULTS: The APACHE II at admission was 22.6±7.2 with a mortality risk of 46.1±27.7%. The mean REE obtained by IC and by the Brandi and Liggett equations were 1699±271, 1815±355 and 1361±277 kcal.day-1 respectively. There were no statistically significant differences between the two methods, with the two means showing a difference of 8.7%. REE values were close for IC x BRANDI (r=0.80), but the IC x LIGGETT correlation was only 0.58. CONCLUSIONS: The results suggest that REE can be easily calculated by obtaining VO2 with the Swan-Ganz catheter and using the Brandi equation even for septic patients under mechanical ventilation. OBJETIVO: O objetivo desse estudo foi o de comparar o consumo de oxigênio em repouso (COR) obtido por calorimetria indireta (CI) com valores do COR calculados por equações preditivas (Brandi e Ligget) que utilizam o consumo de oxigênio (VO2) obtido pelo método de Fick em pacientes sépticos. MÉTODOS. Estudo prospectivo em pacientes sépticos internados em unidade de terapia intensiva de um hospital universitário. Quinze pacientes adultos (onze homens e quatro mulheres). As medidas de VO2 foram realizadas usando um aparelho metabólico portátil conectado ao respirador e por cateter em artéria pulmonar. RESULTADOS: O índice APACHE II na admissão foi 22.6±7.2 com risco de mortalidade de 46.1±27.7%. As médias do COR obtidas por CI e pelas equações de Brandi and Liggett foram, respectivamente, 1699±271, 1815±355 e 1361±277 kcal.day-1 Não se observaram diferenças estatisticamente significantes entre os dois métodos com as duas médias mostrando uma diferenças de 8.7%. Os valores de COR Também foram próximo dos valores de CI x BRANDI (r=0.80), mas a correlação com CI x LIGGETT apenas 0.58. CONCLUSÕES: Os resultados sugerem que o COR pode ser facilmente calculado para obter-se o VO2 com o cateter de Swan-Ganz e pelo uso da equação de Brandi para pacientes sépticos em ventilação mecânica.

At present, the clinical management inflammatory vasoplegia associated to sepsis or anaphylaxis is symptomatic. Volume is expanded by means of administration of fluids, and low blood pressure is managed by means of administration of positive inotropes and vasoconstrictors. This therapeutic approach is mainly associated to the cyclic AMP (cAMP) and, many times the circulatory shock is refractory to high amines concentrations. However, beside of cAMP-dependent vasoreactivity mechanisms there are other two known vasoplegia involved mechanisms: cyclic GMP (cGMP) and hyperpolarization that is less clinically considered. Also, it is possible to speculate about 'probable vasopressin deficiency'. Methylene blue (MB) is the most useful and clinically safe cGMP blocker. We propose a decision tree for diagnosis and institution of this therapeutical approach many times underestimate by intensive care and emergency teams.

The deregulation of inflammatory response during sepsis seems to reflect the overproduction of mediators, which suppress leukocyte functions. We investigated the intracellular mechanisms underlying the inability of neutrophils from severe septic patients to migrate toward chemoattractants. Patients with sepsis (52) and 15 volunteers were prospectively enrolled. Patients presented increased circulating levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)–8, and IL-10. Patients showed reduced neutrophil chemotaxis to formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene B4 (LTB4) or IL-8. No difference in the transcription or expression of the IL-8 receptor, CXCR1, was detected in neutrophils from controls and patients. However, septic neutrophils failed to increase tyrosine phosphorylation and actin polymerization in response to IL-8 or LTB4. In contrast, septic neutrophils, similar to controls, showed phagocytic activity that induced actin polymerization and augmented phosphotyrosine content. Treatment of control neutrophils with cytokines and lipopolysaccharide (LPS) to mimic endogenous septic environment inhibited actin polymerization and tyrosine phosphorylation in response to IL-8 or LTB4. High expression of G protein–coupled receptor kinase 2 (GRK2) and GRK5 was detected in septic neutrophils and control cells treated with cytokines plus LPS. Data suggest that endogenous mediators produced during sepsis might continually activate circulating neutrophils, leading to GRK activation, which may induce neutrophil desensitization to chemoattractants.

Sepsis and septic shock continue to be a major cause of morbidity and mortality in critically ill patients. During the onset of sepsis, several inflammatory mediators, including cytokines, chemokines and nitric oxide are released systemically and mediate most of the pathophysiological events present in sepsis and septic shock, such as cardiovascular dysfunction and target-organ lesions. Polymorphonuclear leukocytes are critical effector cells during the inflammatory process and their migration to the infection focus is extremely important for the local control of bacterial growth and consequently for the prevention of bacterial dissemination. In experimental models and in human sepsis a profound failure of neutrophil migration to the infection focus is observed. It seems that the failure of neutrophil migration is dependent on toll-like receptor 4 (TLR4) and mediated by cytokines and chemokines, which induce the production of nitric oxide that inhibits neutrophil adhesion to venular endothelium and also the neutrophil chemotactic ability.

To compare the oxygen consumption index measured by using indirect calorimetry (VO2I Delta) with a portable metabolic cart and calculated according to Fick's principle (VO2 I Fick) in critically ill patients.Fourteen patients (10 men and 4 women, mean age 39.4 +/- 5.4 years) were analyzed, 5 of them trauma victims and 9 sepsis victims. The following mean scores were obtained for these patients: APACHE II = 21.3+/-1.8, ISS = 24.8+/-6, and sepsis score = 19.6+/-2.3. The mortality risk (odds ratio), calculated from APACHE II, was 41.9+/-7.1%. All patients underwent mechanical ventilation and invasive hemodynamic monitoring with a Swan-Ganz catheter. VO2 was obtained using the 2 methods (VO2I Delta and VO2I Fick) at 4 different times (T1-T4).A good correlation was found between the 2 methods (r=0.77) for the mean of the 4 serial measurements. No statistically significant differences were observed between indirect calorimetry and Fick's equation at T1 (VO2I Delta = 138+/-28 and VO2I Fick = 59+/-38 mL.min-2.m-2, P=0.10) and T3 (VO2I Delta = 144+/-26 and VO2I Fick = 158+/-35 mL.min-2.m-2, P=0.14), but a significant difference was observed at T2 (VO2I Delta = 141+/-27 and VO2I Fick = 155+/-26 mL.min-2.m-2, P=0.03) and T4 (VO2I Delta = 145+/-24 and VO2I Fick = 162+/-26 mL.min-2.m-2, P=0.01).We may state that indirect calorimetry can be used for oxygen consumption analysis in critically ill patients and is as efficient as Fick's reverse equation, with the benefit of being a noninvasive and risk-free procedure.

The severe form of sepsis is associated with multiple organ dysfunction syndrome (MODS), but the precise mechanisms by which MODS develops remain unclear. Neutrophils are essential cellular components of the innate immune system that have conserved roles in bacterial containment. Paradoxically, however, neutrophils also mediate tissue injury in varied human diseases, including sepsis.

Chemokines display a central role in mediating the neutrophil migration to inflammatory focus. Neutrophils respond to CXC chemokines, such as CXCL8, but are usually unresponsive to CC chemokines, such as CCL2. It is known that chemokine responsiveness in neutrophils can be modulated by some inflammatory conditions, such as sepsis. Here, we investigate whether Toll-like receptors (TLRs) modulate the expression of CCR2 in neutrophils and the consequence of this modulation on sepsis onset. Purified neutrophils from septic patients or from WT and CCR2-/- mice subjected to sepsis by cecal ligation and puncture (CLP) and neutrophils from naive mice or healthy humans stimulated with lipoteichoic acid (LTA) or lipopolysaccharide (LPS) were assayed to CCR2 expression by FACS or immunofluorescence and the chemotaxis response to CCL2. Treatments of neutrophils from naive mice or healthy humans with TLR agonists, LTA or LPS, induce an upregulation of the CCR2 expression, leading to CCL2 responsiveness such as chemotaxis and F-actin polymerization. CCL2 expression induced by TLR activation was blocked by NF-κB or synthesis protein inhibitors. Moreover, LTA-induced or LPS-induced CCL2 chemotaxis was not observed in TLR2-/-or TLR4-/- neutrophils, respectively. Interestingly, neutrophils from septic patients or septic mice presented high CCR2 expression and CCL2 responsiveness, when compared with neutrophils from healthy donors or naive mice. In vivo, we found that CCR2-/- mice subjected to severe sepsis by CLP exhibited reduced neutrophil infiltration in the heart, lung and kidney and an enhanced survival rate when compared with WT mice subjected to severe sepsis. Finally, severity of illness of the septic patients, judged by their APACHE II score and PaO2/FiO2 relation, had greater correlation with CCL2 responsiveness by neutrophils (r2 = 0.77, P = 0.001 and r2 = 0.59, P = 0.001, respectively). Our findings demonstrated that TLR activation induced the CCR2 expression and CCL2 responsiveness in human and murine neutrophils, and this expression profile in neutrophils is involved in the detrimental infiltration of these cells in distant tissues during server sepsis. CCR2 blockage is therefore a potential strategy for human sepsis treatment.

The continuous intravenous administration of isotopic bicarbonate (NaH13CO2) has been used for the determination of the retention of the 13CO2 fraction or the 13CO2 recovered in expired air. This determination is important for the calculation of substrate oxidation. The aim of the present study was to evaluate, in critically ill patients with sepsis under mechanical ventilation, the 13CO2 recovery fraction in expired air after continuous intravenous infusion of NaH13CO2 (3.8 micromol/kg diluted in 0.9% saline in ddH2O). A prospective study was conducted on 10 patients with septic shock between the second and fifth day of sepsis evolution (APACHE II, 25.9 +/- 7.4). Initially, baseline CO2 was collected and indirect calorimetry was also performed. A primer of 5 mL NaH13CO2 was administered followed by continuous infusion of 5 mL/h for 6 h. Six CO2 production (VCO2) measurements (30 min each) were made with a portable metabolic cart connected to a respirator and hourly samples of expired air were obtained using a 750-mL gas collecting bag attached to the outlet of the respirator. 13CO2 enrichment in expired air was determined with a mass spectrometer. The patients presented a mean value of VCO2 of 182 +/- 52 mL/min during the steady-state phase. The mean recovery fraction was 0.68 +/- 0.06%, which is less than that reported in the literature (0.82 +/- 0.03%). This suggests that the 13CO2 recovery fraction in septic patients following enteral feeding is incomplete, indicating retention of 13CO2 in the organism. The severity of septic shock in terms of the prognostic index APACHE II and the sepsis score was not associated with the 13CO2 recovery fraction in expired air.