Noninvasive positive-pressure ventilation in clinical practice at a large university-affiliated Brazilian hospital

OBJECTIVES: To describe noninvasive positive-pressure ventilation use in intensive care unit clinical practice, factors associated with NPPV failure and the associated prognosis. METHODS: A prospective cohort study. RESULTS: Medical disorders (59%) and elective surgery (21%) were the main causes for admission to the intensive care unit. The main indications for the initiation of noninvasive positive-pressure ventilation were the following: post-extubation, acute respiratory failure and use as an adjunctive technique to chest physiotherapy. The noninvasive positive-pressure ventilation failure group was older and had a higher Simplified Acute Physiology Score II score. The noninvasive positive-pressure ventilation failure rate was 35%. The main reasons for intubation were acute respiratory failure (55%) and a decreased level of consciousness (20%). The noninvasive positive-pressure ventilation failure group presented a shorter period of noninvasive positive-pressure ventilation use than the successful group [three (2-5) versus four (3-7) days]; they had lower levels of pH, HCO3 and base excess, and the FiO(2) level was higher. These patients also presented lower PaO2:FiO2 ratios; on the last day of support, the inspiratory positive airway pressure and expiratory positive airway pressure were higher. The failure group also had a longer average duration of stay in the intensive care unit [17 (10-26) days vs. 8 (5-14) days], as well as a higher mortality rate (9 vs. 51%). There was an association between failure and mortality, which had an odds ratio (95% CI) of 10.6 (5.93 - 19.07). The multiple logistic regression analysis using noninvasive positive pressure ventilation failure as a dependent variable found that treatment tended to fail in patients with a Simplified Acute Physiology Score II >= 34, an inspiratory positive airway pressure level >= 15 cmH2O and pH<7.40. CONCLUSION: The indications for noninvasive positive-pressure ventilation were quite varied. The failure group had a longer intensive care unit stay and higher mortality. Simplified Acute Physiology Score II >= 34, pH<7.40 and higher inspiratory positive airway pressure levels were associated with failure.

The use of severity indexes to estimate the risk of death in Intensive Care

The Simplified Acute Physiology Score II (SAPS II) and Logistic Organ Dysfunction System (LODS) are instruments used to classify Intensive Care Unit (ICU) inpatients according to the severity of their condition and risk of death, and evaluate the quality of nursing care. The objective of this study is to evaluate and compare the performance of SAPS II and LODS to predict the mortality of patients admitted to the ICU. The participants were 600 patients from four ICUs located in Sao Paulo, Brazil. Receiver Operator Characteristic (ROC) curves were used to compare the performance of the indexes. Results: The areas under the ROC curves of LODS (0.69) and SAPS II (0.71) indicated moderate discriminatory capacity to identify death or survival. No statistically significant differences were found between these areas (p=0.26). In conclusion, there was equivalence between SAPS II and LODS to estimate the risk of death of ICU patients.

Medical adverse events in elderly hospitalized patients: A prospective study

OBJECTIVES: To determine the frequency of medical adverse events in elderly patients admitted to an acute care geriatric unit, the predictive factors of occurrence, and the correlation between adverse events and hospital mortality rates. METHODS: This prospective study included 171 admissions of patients aged 60 years and older in the acute care geriatric unit in a teaching hospital in Brazil between 2007 and 2008. The following variables were assessed at admission: the patient age, gender, number of prescription drugs, geriatric syndromes (e. g., immobility, postural instability, dementia, depression, delirium, and incontinence), comorbidities, functional status (evaluated with the Katz Index of Independence in Activities of Daily Living), and severity of illness (evaluated with the Simplified Acute Physiology Score II). The incidence of delirium, infection, mortality, and the prescription of potentially inappropriate medications (based on the Beers criteria) were assessed during hospitalization. An observer who was uninvolved in patient care reported the adverse events. RESULTS: The mean age of the sample was 78.12 years. A total of 187 medical adverse events occurred in 94 admissions (55%). The predictors of medical adverse events were undetermined. Compared with the patients with no adverse events, the patients with medical adverse events had a significantly longer hospital stay (21.41 +/- 15.08 days versus 10.91 +/- 7.21 days) and a higher mortality rate (39 deaths [41.5%] versus 17 deaths [22.1%]). Mortality was significantly predicted by the Simplified Acute Physiology Score II score (odds ratio [OR] = 1.13, confidence interval [CI] 95%, 1.07 to 1.20), the Katz score (OR = 1.47, CI 95%, 1.18 to 1.83), and medical adverse events (OR = 3.59, CI 95%, 1.55 to 8.30). CONCLUSION: Medical adverse events should be monitored in every elderly hospitalized patient because there is no risk profile for susceptible patients, and the consequences of adverse events are serious, sometimes leading to longer hospital stays or even death.

Desempenho de índices de gravidade para estimar risco de morte em Unidades de Terapia Intensiva

O Simplified Acute Physiology Score II (SAPS II) e o Logistic Organ Dysfunction System (LODS) são instrumentos utilizados para classificar pacientes internados em Unidades de Terapia Intensiva (UTI) conforme a gravidade e o risco de morte, sendo um dos parâmetros da qualidade da assistência de enfermagem. Este estudo teve por objetivo avaliar e comparar as performances do SAPS II e do LODS para predizer mortalidade de pacientes admitidos em UTI. Participaram do estudo 600 pacientes de quatro diferentes UTIs de São Paulo, Brasil. A curva Receiver Operator Characteristic (ROC) foi utilizada para comparar o desempenho discriminatório dos índices. Os resultados foram: as áreas sob a curva do LODS (0.69) e do SAPS II (0.71) apresentaram moderada capacidade discriminatória para predizer mortalidade. Não foi encontrada diferença estatisticamente significativa entre as áreas (p=0,26). Concluiu-se que houve equivalência entre SAPS II e LODS para estimar risco de morte de pacientes em UTI.

Positive fluid balance is associated with reduced survival in critically ill patients with cancer

Background There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients. Method One hundred twenty-two cancer patients were prospectively evaluated for survival during a 30-day period. Univariate (Chi-square, t-test, MannWhitney) and multiple logistic regression analyses were used to identify the admission parameters associated with mortality. Results The mean cumulative fluid balance was significantly higher in non-survivors than in survivors [1675?ml/24?h (4712921) vs. 887?ml/24?h (104557), P?=?0.017]. We used the area under the curve and the intersection of the sensibility and specificity curves to define a cumulative fluid balance value of 1100?ml/24?h. This value was used in the univariate model. In the multivariate model, the following variables were significantly associated with mortality in cancer patients: the Acute Physiology and Chronic Health Evaluation II score at admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.051.26), P?=?0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.293.87), P?=?0.004] and a positive fluid balance higher than 1100?ml/24?h at ICU [OR 5.14; 95% CI (1.4518.24), P?=?0.011]. Conclusion A cumulative positive fluid balance higher than 1100?ml/24?h was independently associated with mortality in patients with cancer. These findings highlight the importance of improving the evaluation of these patients' volemic state and indicate that defined goals should be used to guide fluid therapy.

Do established prognostic factors explain the different mortality rates in ICU septic patients around the world?

Background. The aim of this paper was to clarify if previously established prognostic factors explain the different mortality, rates observed in ICU septic patients around the world. Methods. This is a sub-study from the PROGRESS study, which was an international, prospective, observational registry of ICU patients with severe sepsis. For this study we included 10930 patients from 24 countries that enrolled more than 100 patients in the PROGRESS. The effect of potential prognostic factors on in-hospital mortality was examined using univariate and multivariate logistic regression. The complete set of data was available for 7022 patients, who were considered in the multivariate analysis. Countries were classified according to country, income, development status, and in-hospital mortality terciles. The relationship between countries' characteristics and hospital mortality mortality was evaluated using linear regression. Results. Mean in-hospital mortality was 49.2%. Severe sepsis in-hospital mortality varied widely in different countries, ranging from 30.6% in New Zealand to 80.4% in Algeria. Classification as developed or developing country was not associated with in-hospital mortality (P=0.16), nor were levels of gross national product per capita (P=0.15). Patients in the group of countries with higher in-hospital mortality, had a crude OR for in-hospital death of 2.8 (95% CI 2.5-3.1) in comparison to those in the lower risk group. After adjustments were made for all other independent variables, the OR changed to 2.9 (95% CI 2.5-3.3). Conclusion. Severe sepsis mortality varies widely, in different countries. All known markers of disease severity and prognosis do not fully, explain the international differences in mortality,. Country, income does not explain this disparity, either. Further studies should be developed to verify if other organizational or structural factors account for disparities in patient care and outcomes. (Minerva Anestesiol 2012;78:1215-25)

First-year experience of a Brazilian tertiary medical center in supporting severely ill patients using extracorporeal membrane oxygenation

OBJECTIVES: The aim of this manuscript is to describe the first year of our experience using extracorporeal membrane oxygenation support. METHODS: Ten patients with severe refractory hypoxemia, two with associated severe cardiovascular failure, were supported using venous-venous extracorporeal membrane oxygenation (eight patients) or veno-arterial extracorporeal membrane oxygenation (two patients). RESULTS: The median age of the patients was 31 yr (range 14-71 yr). Their median simplified acute physiological score three (SAPS3) was 94 (range 84-118), and they had a median expected mortality of 95% (range 87-99%). Community-acquired pneumonia was the most common diagnosis (50%), followed by P. jiroveci pneumonia in two patients with AIDS (20%). Six patients were transferred from other ICUs during extracorporeal membrane oxygenation support, three of whom were transferred between ICUs within the hospital (30%), two by ambulance (20%) and one by helicopter (10%). Only one patient (10%) was anticoagulated with heparin throughout extracorporeal membrane oxygenation support. Eighty percent of patients required continuous venous-venous hemofiltration. Three patients (30%) developed persistent hypoxemia, which was corrected using higher positive end-expiratory pressure, higher inspired oxygen fractions, recruitment maneuvers, and nitric oxide. The median time on extracorporeal membrane oxygenation support was five (range 3-32) days. The median length of the hospital stay was 31 (range 3-97) days. Four patients (40%) survived to 60 days, and they were free from renal replacement therapy and oxygen support. CONCLUSIONS: The use of extracorporeal membrane oxygenation support in severely ill patients is possible in the presence of a structured team. Efforts must be made to recognize the necessity of extracorporeal respiratory support at an early stage and to prompt activation of the extracorporeal membrane oxygenation team.

The implementation of the Medical Regulation Office and Mobile Emergency Attendance System and its impact on the gravity profile of non-traumatic afflictions treated in a University Hospital: a research study

Abstract Background The public health system of Brazil is structured by a network of increasing complexity, but the low resolution of emergency care at pre-hospital units and the lack of organization of patient flow overloaded the hospitals, mainly the ones of higher complexity. The knowledge of this phenomenon induced Ribeirão Preto to implement the Medical Regulation Office and the Mobile Emergency Attendance System. The objective of this study was to analyze the impact of these services on the gravity profile of non-traumatic afflictions in a University Hospital. Methods The study conducted a retrospective analysis of the medical records of 906 patients older than 13 years of age who entered the Emergency Care Unit of the Hospital of the University of São Paulo School of Medicine at Ribeirão Preto. All presented acute non-traumatic afflictions and were admitted to the Internal Medicine, Surgery or Neurology Departments during two study periods: May 1996 (prior to) and May 2001 (after the implementation of the Medical Regulation Office and Mobile Emergency Attendance System). Demographics and mortality risk levels calculated by Acute Physiology and Chronic Health Evaluation II (APACHE II) were determined. Results From 1996 to 2001, the mean age increased from 49 ± 0.9 to 52 ± 0.9 (P = 0.021), as did the percentage of co-morbidities, from 66.6 to 77.0 (P = 0.0001), the number of in-hospital complications from 260 to 284 (P = 0.0001), the mean calculated APACHE II mortality risk increased from 12.0 ± 0.5 to 14.8 ± 0.6 (P = 0.0008) and mortality rate from 6.1 to 12.2 (P = 0.002). The differences were more significant for patients admitted to the Internal Medicine Department. Conclusion The implementation of the Medical Regulation and Mobile Emergency Attendance System contributed to directing patients with higher gravity scores to the Emergency Care Unit, demonstrating the potential of these services for hierarchical structuring of pre-hospital networks and referrals.

Prevention of Intradialytic Hypotension in Patients with Acute Kidney Injury Submitted to Sustained Low-Efficiency Dialysis

Objectives: This study evaluated the effects of a protocol aiming to reduce hypotension in acute kidney injury (AKI) patients submitted to sustained low-efficiency dialysis (SLED). Methods: Patients were randomly assigned to two SLED prescriptions-control group, dialysate temperature was 37.0 degrees C with a fixed sodium concentration [138 mEq/L] and ultrafiltration (UF) rate; and profiling group, dialysate temperature was 35.5 degrees C with a variable sodium concentration [150-138 mEq/L] and UF rate. Results: Sixty-two SLED sessions were evaluated (34 in profiling and 28 in control). Patients (n = 31) were similar in terms of gender, age, and Sequential Organ Failure Assessment (SOFA) score. Dialysis time, dialysis dose, and post-dialysis serum sodium were similar in both groups. The profiling group had significantly less hypotension episodes (23% vs. 57% in control, p = 0.009) and achieved higher UF volume (2.23 +/- 1.25 L vs. 1.59 +/- 1.03 L in control, p = 0.04) when compared with control group. Conclusions: SLED protocol with modulation of dialysate temperature, sodium, and UF profiling showed similar efficacy but less intradialytic hypotension when compared with a standard SLED prescription.

Using the National Institute of Health Stroke Scale to Predict Dysphagia in Acute Ischemic Stroke

Background and Purpose: Oropharyngeal dysphagia is a common manifestation in acute stroke. Aspiration resulting from difficulties in swallowing is a symptom that should be considered due to the frequent occurrence of aspiration pneumonia that could influence the patient's recovery as it causes clinical complications and could even lead to the patient's death. The early clinical evaluation of swallowing disorders can help define approaches and avoid oral feeding, which may be detrimental to the patient. This study aimed to create an algorithm to identify patients at risk of developing dysphagia following acute ischemic stroke in order to be able to decide on the safest way of feeding and minimize the complications of stroke using the National Institutes of Health Stroke Scale (NHISS). Methods: Clinical assessment of swallowing was performed in 50 patients admitted to the emergency unit of the University Hospital, Faculty of Medicine of Ribeirao Preto, Sao Paulo, Brazil, with a diagnosis of ischemic stroke, within 48 h after the beginning of symptoms. Patients, 25 females and 25 males with a mean age of 64.90 years (range 26-91 years), were evaluated consecutively. An anamnesis was taken before the patient's participation in the study in order to exclude a prior history of deglutition difficulties. For the functional assessment of swallowing, three food consistencies were used, i.e. pasty, liquid and solid. After clinical evaluation, we concluded whether there was dysphagia. For statistical analysis we used the Fisher exact test, verifying the association between the variables. To assess whether the NIHSS score characterizes a risk factor for dysphagia, a receiver operational characteristics curve was constructed to obtain characteristics for sensitivity and specificity. Results: Dysphagia was present in 32% of the patients. The clinical evaluation is a reliable method of detection of swallowing difficulties. However, the predictors of risk for the swallowing function must be balanced, and the level of consciousness and the presence of preexisting comorbidities should be considered. Gender, age and cerebral hemisphere involved were not significantly associated with the presence of dysphagia. NIHSS, Glasgow Coma Scale, and speech and language changes had a statistically significant predictive value for the presence of dysphagia. Conclusions: The NIHSS is highly sensitive (88%) and specific (85%) in detecting dysphagia; a score of 12 may be considered as the cutoff value. The creation of an algorithm to detect dysphagia in acute ischemic stroke appears to be useful in selecting the optimal feeding route while awaiting a specialized evaluation. Copyright (C) 2012 S. Karger AG, Basel

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 +/- 1.11) to UIP (23.45 +/- 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.

Use of Demonstrably Effective Therapies in the Treatment of Acute Coronary Syndromes: Comparison between Different Brazilian Regions. Analysis of the Brazilian Registry on Acute Coronary Syndromes (BRACE)

Background: Little is known in our country about regional differences in the treatment of acute coronary disease. Objective: To analyze the behavior regarding the use of demonstrably effective regional therapies in acute coronary disease. Methods: A total of 71 hospitals were randomly selected, respecting the proportionality of the country in relation to geographic location, among other criteria. In the overall population was regionally analyzed the use of aspirin, clopidogrel, ACE inhibitors / AT1 blocker, beta-blockers and statins, separately and grouped by individual score ranging from 0 (no drug used) to 100 (all drugs used). In myocardial infarction with ST elevation (STEMI) regional differences were analyzed regarding the use of therapeutic recanalization (fibrinolytics and primary angioplasty). Results: In the overall population, within the first 24 hours of hospitalization, the mean score in the North-Northeast (70.5 +/- 22.1) was lower (p < 0.05) than in the Southeast (77.7 +/- 29.5), Midwest (82 +/- 22.1) and South (82.4 +/- 21) regions. At hospital discharge, the score of the North-Northeast region (61.4 +/- 32.9) was lower (p < 0.05) than in the Southeast (69.2 +/- 31.6), Midwest (65.3 +/- 33.6) and South (73.7 +/- 28.1) regions; additionally, the score of the Midwest was lower (p < 0.05) than the South region. In STEMI, the use of recanalization therapies was highest in the Southeast (75.4%, p = 0.001 compared to the rest of the country), and lowest in the North-Northeast (52.5%, p < 0.001 compared to the rest of the country). Conclusion: The use of demonstrably effective therapies in the treatment of acute coronary disease is much to be desired in the country, with important regional differences.

Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice

Jun JC, Shin MK, Yao Q, Bevans-Fonti S, Poole J, Drager LF, Polotsky VY. Acute hypoxia induces hypertriglyceridemia by decreasing plasma triglyceride clearance in mice. Am J Physiol Endocrinol Metab 303: E377-E388, 2012. First published May 22, 2012; doi:10.1152/ajpendo.00641.2011.-Obstructive sleep apnea (OSA) induces intermittent hypoxia (IH) during sleep and is associated with elevated triglycerides (TG). We previously demonstrated that mice exposed to chronic IH develop elevated TG. We now hypothesize that a single exposure to acute hypoxia also increases TG due to the stimulation of free fatty acid (FFA) mobilization from white adipose tissue (WAT), resulting in increased hepatic TG synthesis and secretion. Male C57BL6/J mice were exposed to FiO(2) = 0.21, 0.17, 0.14, 0.10, or 0.07 for 6 h followed by assessment of plasma and liver TG, glucose, FFA, ketones, glycerol, and catecholamines. Hypoxia dose-dependently increased plasma TG, with levels peaking at FiO(2) = 0.07. Hepatic TG levels also increased with hypoxia, peaking at FiO(2) = 0.10. Plasma catecholamines also increased inversely with FiO(2). Plasma ketones, glycerol, and FFA levels were more variable, with different degrees of hypoxia inducing WAT lipolysis and ketosis. FiO(2) = 0.10 exposure stimulated WAT lipolysis but decreased the rate of hepatic TG secretion. This degree of hypoxia rapidly and reversibly delayed TG clearance while decreasing [H-3]triolein-labeled Intralipid uptake in brown adipose tissue and WAT. Hypoxia decreased adipose tissue lipoprotein lipase (LPL) activity in brown adipose tissue and WAT. In addition, hypoxia decreased the transcription of LPL, peroxisome proliferator-activated receptor-gamma, and fatty acid transporter CD36. We conclude that acute hypoxia increases plasma TG due to decreased tissue uptake, not increased hepatic TG secretion.

N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation

Campos R, Shimizu MH, Volpini RA, de Bragan a AC, Andrade L, Lopes FD, Olivo C, Canale D, Seguro AC. N-acetylcysteine prevents pulmonary edema and acute kidney injury in rats with sepsis submitted to mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 302: L640-L650, 2012. First published January 20, 2012; doi: 10.1152/ajplung.00097.2011.-Sepsis is a common cause of acute kidney injury (AKI) and acute lung injury. Oxidative stress plays as important role in such injury. The aim of this study was to evaluate the effects that the potent antioxidant N-acetylcysteine (NAC) has on renal and pulmonary function in rats with sepsis. Rats, treated or not with NAC (4.8 g/l in drinking water), underwent cecal ligation and puncture (CLP) 2 days after the initiation of NAC treatment, which was maintained throughout the study. At 24 h post-CLP, renal and pulmonary function were studied in four groups: control, control + NAC, CLP, and CLP + NAC. All animals were submitted to low-tidal-volume mechanical ventilation. We evaluated respiratory mechanics, the sodium cotransporters Na-K-2Cl (NKCC1) and the alpha-subunit of the epithelial sodium channel (alpha-ENaC), polymorphonuclear neutrophils, the edema index, oxidative stress (plasma thiobarbituric acid reactive substances and lung tissue 8-isoprostane), and glomerular filtration rate. The CLP rats developed AKI, which was ameliorated in the CLP + NAC rats. Sepsis-induced alterations in respiratory mechanics were also ameliorated by NAC. Edema indexes were lower in the CLP + NAC group, as was the wet-to-dry lung weight ratio. In CLP + NAC rats, alpha-ENaC expression was upregulated, whereas that of NKCC1 was downregulated, although the difference was not significant. In the CLP + NAC group, oxidative stress was significantly lower and survival rates were significantly higher than in the CLP group. The protective effects of NAC (against kidney and lung injury) are likely attributable to the decrease in oxidative stress, suggesting that NAC can be useful in the treatment of sepsis.

Erythropoietin prevents sepsis-related acute kidney injury in rats by inhibiting NF-kappa B and upregulating endothelial nitric oxide synthase

de Souza ACCP, Volpini RA, Shimizu MH, Sanches TR, Camara NOS, Semedo P, Rodrigues CE, Seguro AC, Andrade L. Erythropoietin prevents sepsis-related acute kidney injury in rats by inhibiting nuclear factor-kappa B and upregulating endothelial nitric oxide synthase. Am J Physiol Renal Physiol 302: F1045-F1054, 2012. First published January 11, 2012; doi:10.1152/ajprenal.00148.2011.-The pathophysiology of sepsis involves complex cytokine and inflammatory mediator networks, a mechanism to which NF-kappa B activation is central. Downregulation of endothelial nitric oxide synthase (eNOS) contributes to sepsis-induced endothelial dysfunction. Erythropoietin (EPO) has emerged as a major tissue-protective cytokine in the setting of stress. We investigated the role of EPO in sepsis-related acute kidney injury using a cecal ligation and puncture (CLP) model. Wistar rats were divided into three primary groups: control (sham-operated); CLP; and CLP + EPO. EPO (4,000 IU/kg body wt ip) was administered 24 and 1 h before CLP. Another group of rats received N-nitro-L-arginine methyl ester (L-NAME) simultaneously with EPO administration (CLP + EPO + L-NAME). A fifth group (CLP + EPOtreat) received EPO at 1 and 4 h after CLP. At 48 h postprocedure, CLP + EPO rats presented significantly higher inulin clearance than did CLP and CLP + EPO + L-NAME rats; hematocrit levels, mean arterial pressure, and metabolic balance remained unchanged in the CLP + EPO rats; and inulin clearance was significantly higher in CLP + EPOtreat rats than in CLP rats. At 48 h after CLP, creatinine clearance was significantly higher in the CLP + EPO rats than in the CLP rats. In renal tissue, pre-CLP EPO administration prevented the sepsis-induced increase in macrophage infiltration, as well as preserving eNOS expression, EPO receptor (EpoR) expression, IKK-alpha activation, NF-kappa B activation, and inflammatory cytokine levels, thereby increasing survival. We conclude that this protection, which appears to be dependent on EpoR activation and on eNOS expression, is attributable, in part, to inhibition of the inflammatory response via NF-kappa B downregulation.