Anibal Basile-Filho

Interleukin-33 attenuates sepsis by enhancing neutrophil influx to the site of infection

Sepsis is a systemic inflammatory condition following bacterial infection with a high mortality rate and limited therapeutic options. Here we show that interleukin-33 (IL-33) reduces mortality in mice with experimental sepsis from cecal ligation and puncture (CLP). IL-33–treated mice developed increased neutrophil influx into the peritoneal cavity and more efficient bacterial clearance than untreated mice. IL-33 reduced the systemic but not the local proinflammatory response, and it did not induce a T helper type 1 (TH1) to TH2 shift. The chemokine receptor CXCR2 is crucial for recruitment of neutrophils from the circulation to the site of infection. Activation of Toll-like receptors (TLRs) in neutrophils downregulates CXCR2 expression and impairs neutrophil migration. We show here that IL-33 prevents the downregulation of CXCR2 and inhibition of chemotaxis induced by the activation of TLR4 in mouse and human neutrophils. Furthermore, we show that IL-33 reverses the TLR4-induced reduction of CXCR2 expression in neutrophils via the inhibition of expression of G protein–coupled receptor kinase-2 (GRK2), a serine-threonine protein kinase that induces internalization of chemokine receptors. Finally, we find that individuals who did not recover from sepsis had significantly more soluble ST2 (sST2, the decoy receptor of IL-33) than those who did recover. Together, our results indicate a previously undescribed mechanism of action of IL-33 and suggest a therapeutic potential of IL-33 in sepsis.

Dissemination of blaKPC-2 by the Spread of Klebsiella pneumoniae Clonal Complex 258 Clones (ST258, ST11, ST437) and Plasmids (IncFII, IncN, IncL/M) among Enterobacteriaceae Species in Brazil

ABSTRACT This article reports the spread of blaKPC-2 in the Sao Paulo and Rio de Janeiro states, facilitated by globally spread K. pneumoniae clonal complex 258 (CC258) clones (ST258, ST11, and ST437) and a diversity of plasmids (IncFII, IncN, and IncL/M, two untypeable plasmids carrying Tn4401a or Tn4401b) successfully disseminated among species of the Enterobacteriaceae (Enterobacter cloacae, Serratia marcescens, and Citrobacter freundii). It also constitutes the first description of sequence type 258 (ST258) in Brazil, which was associated with a nosocomial hospital outbreak in Ribeirao Preto city.

Essential Role of CCR2 in Neutrophil Tissue Infiltration and Multiple Organ Dysfunction in Sepsis

RATIONALEnSepsis 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.nnnOBJECTIVESnWe investigated the role of the chemokine receptor CCR2 in driving neutrophil infiltration and eliciting tissue damage in remote organs during sepsis.nnnMETHODSnSepsis 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.nnnMEASUREMENTS AND MAIN RESULTSnCCR2 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.nnnCONCLUSIONSnCollectively, 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.

Effectiveness of Oral Rinse with Chlorhexidine in Preventing Nosocomial Respiratory Tract Infections among Intensive Care Unit Patients

OBJECTIVEnTo evaluate the effectiveness of the oral application of a 0.12% solution of chlorhexidine for prevention of respiratory tract infections among intensive care unit (ICU) patients.nnnDESIGNnThe study design was a double-blind, randomized, placebo-controlled trial.nnnSETTINGnThe study was performed in an ICU in a tertiary care hospital at a public university. PATIENTS. Study participants comprised 194 patients admitted to the ICU with a prospective length of stay greater than 48 hours, randomized into 2 groups: those who received chlorhexidine (n = 98) and those who received a placebo (n = 96).nnnINTERVENTIONnOral rinses with chlorhexidine or a placebo were performed 3 times a day throughout the duration of the patients stay in the ICU. Clinical data were collected prospectively.nnnRESULTSnBoth groups displayed similar baseline clinical features. The overall incidence of respiratory tract infections (RR, 1.0 [95% confidence interval [CI], 0.63-1.60]) and the rates of ventilator-associated pneumonia per 1,000 ventilator-days were similar in both experimental and control groups (22.6 vs 22.3; P = .95). Respiratory tract infection-free survival time (7.8 vs 6.9 days; P = .61), duration of mechanical ventilation (11.1 vs 11.0 days; P = .61), and length of stay (9.7 vs 10.4 days; P = .67) did not differ between the chlorhexidine and placebo groups. However, patients in the chlorhexidine group exhibited a larger interval between ICU admission and onset of the first respiratory tract infection (11.3 vs 7.6 days; P = .05). The chances of surviving the ICU stay were similar (RR, 1.08 [95% CI, 0.72-1.63]).nnnCONCLUSIONnOral application of a 0.12% solution of chlorhexidine does not prevent respiratory tract infections among ICU patients, although it may retard their onset.

Mechanical ventilation mode (volume × pressure) does not change the variables obtained by indirect calorimetry in critically ill patients ☆

PURPOSEnThe aim of the study was to analyze the difference between the results obtained by indirect calorimetry (IC) using volume-controlled and pressure-controlled mechanical ventilation in 2 different ventilators and to characterize the variables achieved by IC after well-defined changes in minute volume (Vm).nnnMATERIALS AND METHODSnProspective study of 20 critically ill patients under volume-controlled (n = 15) or pressure-controlled (n = 5) mechanical ventilation. Three IC measurements of 45 minutes each were taken; values of oxygen consumption (Vo(2)), carbon dioxide production (Vco(2)), Vm, resting energy expenditure (REE), and respiratory quotient (RQ) were obtained. For the last measurement, Vm was set at 20% above the baseline.nnnRESULTSnThere were no differences between the results obtained by IC during volume-controlled and pressure-controlled mechanical ventilation. The most relevant changes in the variables obtained by IC before and after intervention in Vm were a significant increase in Vco(2) (from 165 to 177 mL·min(-1); P < .01), a decrease in Paco(2) (from 38.49 to 28.46 mm Hg; P < .01), and a rise in pH (from 7.41 to 7.49; P < .01). There were no alterations in Vo(2), REE, or RQ.nnnCONCLUSIONSnVentilators and ventilation modes do not influence the IC measurements. The observed changes have no clinical effects and are reversible, provided that increased Vm is maintained for no longer than 45 minutes.

Can an adequate energy intake be able to reverse the negative nitrogen balance in mechanically ventilated critically ill patients

PURPOSEnAdequate energy provision and nitrogen losses prevention of critically ill patients are essentials for treatment and recovery. The aims of this study were to evaluate energy expenditure (EE) and nitrogen balance (NB) of critically ill patients, to classify adequacy of energy intake (EI), and to verify adequacy of EI capacity to reverse the negative NB.nnnMETHODSnSeventeen patients from an intensive care unit were evaluated within a 24-hour period. Indirect calorimetry was performed to calculate patients EE and Kjeldhal for urinary nitrogen analysis. The total EI and protein intake were calculated from the standard parenteral and enteral nutrition infused. Underfeeding was characterized as EI 90% or less and overfeeding as 110% or greater of EE. The adequacy of the EI (EI EE(-1) × 100) and the NB were estimated and associated with each other by Spearman coefficient.nnnRESULTSnThe mean EE was 1515 ± 268 kcal d(-1), and most of the patients (11/14) presented a negative NB (-8.2 ± 4.7 g.d(-1)). A high rate (53%) of inadequate energy intake was found, and a positive correlation between EI EE(-1) and NB was observed (r = 0.670; P = .007).nnnCONCLUSIONnThe results show a high rate of inadequate EI and negative NB, and equilibrium between EI and EE may improve NB. Indirect calorimetry can be used to adjust the energy requirements in the critically ill patients.

Comparison of Acute Physiology and Chronic Health Evaluation II Death Risk, Child-Pugh, Charlson, and Model for End-stage Liver Disease Indexes to Predict Early Mortality After Liver Transplantation

OBJECTIVEnThis study sought to determine which prognostic index was the most efficient to predict early (1-month) mortality of patients undergoing orthotopic liver transplantation (OLT).nnnMATERIALS AND METHODSnThis retrospective study included 63 patients including 49 males and 14 females of overall median age 51.6 ± 9.7 years who were admitted to the intensive care unit (ICU) of a tertiary hospital. The Acute Physiology and Chronic Health Evaluation II (APACHE II) death risk, Child-Pugh, Charlson, and Model for End-stage Liver Disease (MELD) indices pre-OLT and post-OLT were analyzed by generation of receiver operating characteristic (ROC) curves to determine the area under the ROC curve (AUC), as a predictive factor for each index. The level of significance was set at P < .05.nnnRESULTSnThe general 1-month posttransplantation mortality rate of OLT patients was 19% (n = 12 p). The AUC was 0.81 (confidence interval [CI] = 0.66-0.96; sensitivity = 72.5; specificity = 83.3) for APACHE II death risk; 0.74 (CI = 0.57-0.92; sensitivity = 76.5; specificity = 66.7) for MELD post-OLT; 0.70 (CI = 0.54-0.85; sensitivity = 64.7; specificity = 66.7) for Child-Pugh; 0.57 (CI = 0.36-0.78; sensitivity = 74.5; specificity = 50.0) for Charlson; and 0.50 (CI = 0.32-0.69; sensitivity = 98.0; specificity = 16.7) for MELD Pre-OLT.nnnCONCLUSIONnAmong the studied indices, the APACHE II death risk scoring system was the most effective to predict early mortality after OLT.

Harris-Benedict equation for critically ill patients: Are there differences with indirect calorimetry?

PURPOSEnThe aim of this study was to compare the measured energy expenditure (EE) and the estimated basal EE (BEE) in critically ill patients.nnnMATERIALS AND METHODSnSeventeen patients from an intensive care unit were randomly evaluated. Indirect calorimetry was performed to calculate patients EE, and BEE was estimated by the Harris-Benedict formula. The metabolic state (EE/BEE x 100) was determined according to the following criteria: hypermetabolism, more than 130%; normal metabolism, between 90% and 130%; and hypometabolism, less than 90%. To determine the limits of agreement between EE and BEE, we performed a Bland-Altman analysis.nnnRESULTSnThe average EE of patients was 6339 +/- 1119 kJ/d. Two patients were hypermetabolic (11.8%), 4 were hypometabolic (23.5%), and 11 normometabolic (64.7%). Bland-Altman analysis showed a mean of -126 +/- 2135 kJ/d for EE and BEE. Only one patient was outside the limits of agreement between the 2 methods (indirect calorimetry and Harris-Benedict).nnnCONCLUSIONSnThe calculation of energy needs can be done with the equation of Harris-Benedict associated with lower values of correction factors (approximately 10%) to avoid overfeeding, with constant monitoring of anthropometric and biochemical parameters to assess the nutritional changing and adjust the infusion of energy.

The use of perioperative serial blood lactate levels, the APACHE II and the postoperative MELD as predictors of early mortality after liver transplantation

PURPOSEnTo evaluate the accuracy of different parameters in predicting early (one-month) mortality of patients submitted to orthotopic liver transplantation (OLT).nnnMETHODSnThis is a retrospective study of forty-four patients (38 males and 10 females, mean age of 52.2 ± 8.9 years) admitted to the Intensive Care Unit of a tertiary hospital. Serial lactate blood levels, APACHE II, MELD post-OLT, creatinine, bilirubin and INR parameters were analyzed by receiver-operator characteristic (ROC) curves as evidenced by the area under the curve (AUC). The level of significance was set at 0.05.nnnRESULTSnThe mortality of OLT patients within one month was 17.3%. Differences in blood lactate levels became statistically significant between survivors and nonsurvivors at the end of the surgery (p<0.05). The AUC was 0.726 (95%CI = 0.593-0.835) for APACHE II (p = 0.02); 0.770 (95%CI = 0.596-0.849) for blood lactate levels (L7-L8) (p = 0.03); 0.814 (95%CI = 0.690-0.904) for MELD post-OLT (p < 0.01); 0.550 (95%CI = 0.414-0.651) for creatinine (p = 0.64); 0.705 (95%CI = 0.571-0.818) for bilirubin (p = 0.05) and 0.774 (95%CI = 0.654-0.873) for INR (p = 0.02).nnnCONCLUSIONnAmong the studied parameters, MELD post-OLT was more effective in predicting early mortality after OLT.

Correlação entre o consumo de oxigênio obtido pelo método de Fick e pela calorimetria indireta no paciente grave

OBJECTIVEnTo compare the oxygen consumption index measured by using indirect calorimetry (VO2I Delta) with a portable metabolic cart and calculated according to Ficks principle (VO2 I Fick) in critically ill patients.nnnMETHODSnFourteen 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).nnnRESULTSnA 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 Ficks 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).nnnCONCLUSIONnWe may state that indirect calorimetry can be used for oxygen consumption analysis in critically ill patients and is as efficient as Ficks reverse equation, with the benefit of being a noninvasive and risk-free procedure.