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Eliezer Silva

Publications and source records attributed to Eliezer Silva.

10 recordsLinked to original sources
PubMed2006

Variant IRAK-1 haplotype is associated with increased nuclear factor-kappaB activation and worse outcomes in sepsis.

RATIONALE: The IL-1 receptor-associated kinase (IRAK-1) plays a central role in TLR2- and TLR4-induced activation of nuclear factor (NF)-kappaB, a critical event in the transcriptional regulation of many sepsis-associated proinflammatory mediators. There are two haplotypes for the IRAK-1 gene in Caucasians, with the variant haplotype consisting of five intron single-nucleotide polymorphisms (SNPs) and three exon SNPs. OBJECTIVES: To examine the functional significance of the IRAK-1 variant haplotype in modifying nuclear translocation of NF-kappaB and affecting outcomes from sepsis. MEASUREMENTS AND MAIN RESULTS: One hundred fifty-five Caucasian patients with sepsis were included. Twenty-one (14%) were homozygous for the IRAK-1 variant haplotype as determined by a SNP in which T is replaced with C at nucleotide 1,595 within exon 12 of the IRAK-1 gene. The IRAK-1 variant haplotype was associated with increased nuclear levels of NF-kappaB in LPS-stimulated peripheral blood neutrophils from patients with sepsis compared with that found in patients with wild-type IRAK-1 haplotype (p=0.0009). There was an increased incidence of shock (p=0.047) (odds ratio [OR], 2.9; 95% confidence interval [CI], 1.1-7.7), greater requirement for more prolonged mechanical ventilator support (p=0.04) (OR, 2.7; 95% CI, 1.05-6.9), and higher 60-d mortality (p=0.05) (OR, 2.7; 95% CI, 1.0-6.8) in patients with the IRAK-1 variant haplotype compared with wild type. CONCLUSIONS: These results indicate that the IRAK-1 variant haplotype is functionally significant in patients with sepsis, being associated with increased nuclear translocation of NF-kappaB, more severe organ dysfunction, and higher mortality.

Adolescent↗
PubMed2006

Variation in amplitude of central venous pressure curve induced by respiration is a useful tool to reveal fluid responsiveness in postcardiac surgery patients.

We tested the hypothesis that the dynamic evaluation of central venous pressure (CVP) amplitude could be a reliable predictor of fluid responsiveness in patients under mechanical ventilation, similar to the variation of arterial pulse pressure (DeltaPp). Thirty postcardiac surgery patients, under mechanical ventilation, were evaluated. The percentual difference between inspiratory (Ppins) and expiratory pulse pressure (Ppins) was so calculated: DeltaPp (%) = 100 x (Ppins - Ppexp)/[(Ppins + Ppexp)/2]. The respiratory variation of CVP curves amplitude were calculated by determining the percentual difference between inspiratory (CVPpins) and expiratory (CVPpexp) variation using vena cava "pressure" collapsibility index according the following formula: Cvci (%) = [(CVPpexp - CVPpins)/CVPpexp] x 100. There was a correlation between DeltaPp and Cvci (Pearson correlation coefficient, r = 0.45). Receiver operating characteristic curves showed that the Cvci value more than or equal to 5% predicted DeltaPp more than or equal to 13% with 91% specificity, 89% sensitivity, and AUC of 0.90. Therefore, Cvci presented a good agreement with DeltaPp (kappa = 0.76) to identify potential fluid responders (patients with DeltaPp > or =13%). In 9 potential fluid responders, both DeltaPp and Cvci significantly decreased from 18% +/- 8% to 8% +/- 6% (P < 0.004) and 23% +/- 15% to 7% +/- 6% (P < 0.004), respectively, after fluid replacement. Our findings suggest that vena cava "pressure" collapsibility index can be used as a marker of fluid responsiveness in postcardiac surgery patients under mechanical ventilation, such as arterial pulse pressure respiratory variation.

Aged↗
PubMed2006

Low hematocrit impairs gastric mucosal CO2 removal during experimental severe normovolemic hemodilution.

OBJECTIVE: The net effects of acute normovolemic hemodilution with different hemoglobin levels on splanchnic perfusion have not been elucidated. The hypothesis that during moderate and severe normovolemic hemodilution, systemic and splanchnic hemodynamic parameters, oxygen-derived variables, and biochemical markers of anaerobic metabolism do not reflect the adequacy of gastric mucosa, was tested in this study. METHODS: Twenty one anesthetized mongrel dogs (16 +/- 1 kg) were randomized to controls (CT, n = 7, no hemodilution), moderate hemodilution (hematocrit 2 5% +/- 3%, n = 7) or severe hemodilution (severe hemodilution, hematocrit 15% +/- 3%, n = 7), through an isovolemic exchange of whole blood and 6% hydroxyethyl starch, at a 20 mL/min rate, to the target hematocrit. The animals were followed for 120 min after hemodilution. Cardiac output (CO, L/min), portal vein blood flow (PVF, mL/min), portal vein-arterial and gastric mucosa-arterial CO2 gradients (PV-artCO2 and PCO2 gap, mm Hg, respectively) were measured throughout the experiment. RESULTS: Exchange blood volumes were 33.9 +/- 3.3 and 61.5 +/- 5.8 mL/kg for moderate hemodilution and severe hemodilution, respectively. Arterial pressure and systemic and regional lactate levels remained stable in all groups. There were initial increases in cardiac output and portal vein blood flow in both moderate hemodilution and severe hemodilution; systemic and regional oxygen consumption remained stable largely due to increases in oxygen extraction rate. There was a significant increase in the PCO2-gap value only in severe hemodilution animals. CONCLUSION: Global and regional hemodynamic stability were maintained after moderate and severe hemodilution. However, a very low hematocrit induced gastric mucosal acidosis, suggesting that gastric mucosal CO2 monitoring may be useful during major surgery or following trauma.

Animals↗
PubMed2006

Epidemiology of severe sepsis around the world.

Severe sepsis is an ongoing challenge for clinicians and health-care administrators mainly because is associated with a high incidence, mortality rate and costs. In recent years, several epidemiological studies about the incidence of sepsis have come out in different and prestigious journals. However, it is not advisable to draw direct conclusions from those studies considering methodological flaws or even different approaches. Hence, we have to be familiar with those obstacles and know how to overcome them. This review paper highlights the methods which have been used in these studies and depicts the results of occurrence rate or incidence of sepsis in countries and in intensive care units.

Epidemiologic Methods↗
PubMed2006

Surviving sepsis campaign: a project to change sepsis trajectory.

Sepsis is an acute and severe disease associated with early and late high mortality, high and growing prevalence, and impressive costs. In October 2002, during the European Society of Intensive Care Medicine annual congress, the Surviving Sepsis Campaign was launched through a "Barcelona Declaration" -- a document calling critical care providers, governments, health agencies and lay people to join the fight against sepsis. The aim of the campaign was to reduce the sepsis mortality rate by 25% within 5 years (actually, this deadline has been ended from 2007 to 2009). In 2003, a group of international critical care and infectious disease experts in the diagnosis and management of infection and sepsis met to develop guidelines that the bedside clinician could use to improve the outcome of severe sepsis and septic shock. A comprehensive document created from the committee's deliberations was published in prestigious journals. Thus, the SSC is a global, multi-organizational initiative to fight sepsis and undoubtedly, this campaign is a historic step for critical care medicine. This paper highlights the recommendations and the strategies proposed by SSC to implement them in intensive care units.

Humans↗
PubMed2006

Pathogenesis-oriented targets for adjunctive therapy.

The outcome of patients with sepsis arises from multiple factors affecting both the host and the invading microorganisms. Even within the setting of adequate antimicrobial use, patients still die of sepsis. Thus, strategies focusing on further therapy targets are an important area of interest for basic and clinical research. Although such adjunctive sepsis therapy has failed to achieve consistent better survival rates so far, the progress in understanding of the pathophysiology of sepsis seen in recent years is so profound, that the possibility that a new and effective treatment may arise should be warmly considered. Indeed, it may be considered that efficacious interventions, such as early and vigorous fluid replacement, strict blood glucose control, low-dose corticosteroid reposition, protective mechanical ventilation and activated-protein C are pathogenic-oriented targets of therapy. In this paper we aim to review some aspects of the pathogenesis of sepsis, focusing on possible targets for adjunctive therapy. Published clinical trials and experimental data supporting such trials are commented on.

Animals↗
PubMed2005

Early changes in organ function predict eventual survival in severe sepsis.

OBJECTIVE: Early identification and treatment of severe sepsis can significantly reduce mortality rate. We hypothesized that a risk prediction model based on early (baseline to day 1 of study) response to standard care should be significantly related to 28-day survival. DESIGN: Analysis of organ dysfunction data from two placebo-controlled severe sepsis trials (PROWESS and secretory phospholipase A2 inhibitor trials). SETTING: Research laboratory. PATIENTS: The placebo arms of two randomized, double-blind sepsis trials were combined (n = 1036). These patients met criteria for severe sepsis and received supportive standard intensive care and fluid resuscitation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Sequential Organ Failure Assessment (SOFA) scores were calculated daily using the most aberrant physiologic or laboratory variables. Baseline and post-baseline SOFA scores categorized as improved, unchanged, or worsened were used in regression analyses correlating organ dysfunction changes with 28-day mortality. Improvement in cardiovascular (p = .0010), renal (p < .0001), or respiratory (p = .0469) function from baseline to day 1 was significantly related to survival. Odds ratios (95% confidence intervals) associated with improved vs. worsened respiratory, cardiovascular, or renal function before start of day 1 were 0.56 (0.35-0.91), 0.33 (0.18-0.59), and 0.30 (0.17-0.52), respectively. Continued improvement in cardiovascular function before start of day 2 and start of day 3 was associated with further improvement in survival (p <. 0001), with odds ratios of 0.15 (0.06-0.39) and 0.11 (0.04-0.31) for patients who improved compared with those who worsened. No other organ system was retained in the model, and improvement beyond day 1 in any other organ function did not add to the model's predictive power. CONCLUSIONS: These analyses suggest that outcomes for patients with severe sepsis are closely related to early (baseline to day 1 here) improvement, or lack thereof, in organ function. Also, clinical improvement on subsequent days may have little additional impact on the likelihood of survival.

Adult↗
PubMed2004

Cardiac output determination during experimental hemorrhage and resuscitation using a transesophageal Doppler monitor.

Transesophageal Doppler (TED) monitoring has been considered a noninvasive and accurate alternative to pulmonary artery catheterization for volume replacement and cardiac output measurement in patients undergoing major surgery. This study tested the hypothesis that TED can accurately predict cardiac output during hemorrhage, shock, and resuscitation, by comparing it to total pulmonary artery blood flow (PABF) and to standard intermittent bolus cardiac output (ICO). In eight anesthetized dogs (18 +/- 1.0 kg), PABF was measured with an ultrasonic flowprobe while ICO and mixed venous O2 saturation (SvO2) were measured through a Swan-Ganz catheter. A TED probe (CardioQ, Deltex Medical Inc., Irving, TX, U.S.A.), designed for adult use (minimum 30 kg, 16 years), was placed in midesophageous to evaluate stroke volume. A graded hemorrhage (20 mL/min) was produced (H5-H35) to a mean arterial pressure (MAP) of 40 mm Hg and maintained by additional blood removal for 30 min (S1-S30). Total shed blood volume was retransfused (541 +/- 54.2 mL) over 30 min (T5-T30), after which a massive hemorrhage, 100 mL/min rate, was produced over 10 min (MH5-MH10). In general, TED overestimated PABF (r2 = 0.3472), but changes in TED paralleled PABF throughout the experimental protocol, particularly during massive hemorrhage (r2 = 0.9001). We concluded that TED accurately reflected the direction and magnitude of the changes of cardiac output over time during abrupt hemodynamic changes. Probes designed for lower weights and smaller aortas may improve its accuracy in medium size animal models under less dramatic alterations induced by hemorrhage, shock, and resuscitation.

Animals↗
PubMedDate not supplied

Sustained gastric mucosal acidosis after hemorrhage in spite of rapid hemodynamic restoration with blood or hypertonic/hyperoncotic solution.

Splanchnic hypoperfusion has been implicated as the motor of multiple organ dysfunction. Hypertonic saline has shown to benefit microcirculatory blood flow. In hemorrhaged animals, we tested the hypothesis that small-volume 3% NaCl/10% dextran 40 (3%HSD) promotes global and regional improvements, including gastric mucosal acidosis reversal. Seventeen dogs (18.8 +/- 1.2 kg) were bled (20 mL/min) to a mean arterial pressure of 40-45 mm Hg, which was maintained at these levels for 15 min. They were randomly assigned to two groups: Blood (n = 9), total shed blood retransfused at 40 mL/min; or a 4-min bolus injection of 3%HSD (n = 8), in a volume equivalent to 25% of total shed blood. All animals were followed for 30 min thereafter. Gastric mucosal PCO2 (gas tonometry), portal vein PCO2, superior mesenteric artery blood flow (SMA, ultrasonic flowprobes), and systemic and regional O2-derived variables were evaluated throughout the protocol. Hemorrhage induced significant reductions of arterial pressure, cardiac output, and SMA blood flow, while portal-arterial and gastric-arterial PCO2 gradients increased. Total shed blood transfusion, as well as 3%HSD bolus injection, promptly restored all parameters, except for the increased gastric-arterial PCO2 gradient. We conclude that persistent gastric mucosal acidosis cannot be adequately predicted by global and splanchnic O2 derived variables in following hemorrhage and resuscitation with total shed blood transfusion or small-volume hypertonic-hyperoncotic solution.

Acidosis↗