Stratification to predict the response to antioxidant. / Estratificação para predizer a resposta ao tratamento antioxidante em terapia intensiva: um estudo translacional.

OBJECTIVE: To examine the effectiveness of stratification to identify and target antioxidant therapy for animal models of lethal sepsis and in patients who develop sustained hypotension. METHODS: Rats were subjected to sepsis induced by cecal ligation and puncture. Animals were divided into two groups: those with high and low plasma levels of interleukin-6. Following stratification, N-acetylcysteine plus deferoxamine or saline was administered to animals starting 3 and 12 hours after surgery. N-Acetylcysteine plus deferoxamine or placebo was administered within 12 hours of meeting the inclusion criteria in hypotensive patients. RESULTS: N-Acetylcysteine plus deferoxamine increased survival in the cecal ligation and puncture model when administered 3 and 12 hours after sepsis induction. When dividing animals that received antioxidants using plasma interleukin-6 levels, the protective effect was observed only in those animals with high IL-6 levels. The antioxidant effect of N-acetylcysteine + deferoxamine was similar in the two groups, but a significant decrease in plasma interleukin-6 levels was observed in the high-interleukin-6-level group. Compared with patients treated with antioxidants in the low-interleukin-6 subgroup, those in the high-interleukin-6 subgroup had a lower incidence of acute kidney injury but were not different in terms of acute kidney injury severity or intensive care unit mortality. CONCLUSION: Targeting antioxidant therapy to a high inflammatory phenotype would select a responsive population.

N-acetylcysteine plus deferoxamine for patients with prolonged hypotension does not decrease acute kidney injury incidence: a double blind, randomized, placebo-controlled trial.

BACKGROUND: The aim was to test the primary hypothesis that in patients suffering from shock, treatment with N-acetylcysteine (NAC) plus deferoxamine (DFX) decreases the incidence of acute kidney injury (AKI). METHODS: A double-blind, randomized, placebo-controlled trial was conducted in a general intensive care unit in an academic hospital. Patients were included if they had new-onset hypotension, defined as mean arterial blood pressure <60 mmHg or requirement for vasopressor medication. A loading dose of NAC or placebo of 50 mg/kg in 4 h was administered intravenously. After the loading dose, patients received 100 mg/kg/day for the next 48 h. DFX or placebo was administered once at 1000 mg at a rate of 15/mg/kg/h. The primary outcome was the incidence of AKI. RESULTS: A total of 80 patients were enrolled in the study. The incidence of AKI was 67 % in the placebo arm and 65 % in the treatment group (relative risk (RR) 0.89 (0.35-2.2)). Furthermore, NAC plus DFX was effective in decreasing the severity and duration of AKI, and patients in the treatment group had lower serum creatinine levels at discharge. No severe adverse event associated with treatment was reported. The effects of NAC plus DFX could be secondary to the attenuation of early inflammatory response and oxidative damage. CONCLUSION: The administration of NAC plus DFX to critically ill patients who had a new episode of hypotension did not decrease the incidence of AKI. TRIAL REGISTRATION: Clinicaltrials.gov NCT00870883 (Registered 25 March 2009.).

Hypomagnesemia as a risk factor for the non-recovery of the renal function in critically ill patients with acute kidney injury.

BACKGROUND: The aim of this study was to evaluate the role of hypomagnesemia as a risk factor for the development of acute kidney injury (AKI) and non-recovery of renal function in critically ill patients. METHODS: A cohort study was conducted by collecting data from March to June 2011 in 232 patients who were admitted into an intensive care unit (ICU). Magnesium serum levels were measured daily during ICU stay. Hypomagnesemia was defined as an episode of serum magnesium concentration of <0.70 mmol/L during ICU stay. The Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) criteria were used to define AKI. Renal function recovery was defined as an absence of AKI by the RIFLE criteria over a 48-h period, or at ICU discharge, in the patients who developed AKI during ICU stay. RESULTS: The presence of hypomagnesemia was similar in patients with or without AKI (47 and 62%, respectively, P = 0.36). The presence of hypomagnesemia was higher in patients who did not recover renal function when compared with patients who recovered renal function (70 versus 31%, P = 0.003). A multivariate analysis identified hypomagnesemia as an independent risk factor for non-recovery of renal function (P = 0.005). Patients with and without hypomagnesemia had similar mortality rates (P = 0.63). CONCLUSIONS: Hypomagnesemia was an independent risk factor for non-recovery of renal function in a cohort of critically ill AKI patients.

Desempenho do escore SAPS II em uma unidade de terapia intensiva / The SAPS II performance in an intensive care unit

Introdução: O Simplified Acute Physiology Score (SAPS) é um modelo desenvolvido na França por Le Gall et al. em 1983, modificado para SAPS II em 1993. É composto por 12 variáveis fisiológicas, idade, tipo de admissão e presença de doença crônica. Este estudo tem como objetivo analisar a predição de mortalidade do SAPS II nos pacientes internados na UTI do Hospital São José, Criciúma, SC. Métodos: Estudo prospectivo de coorte realizado entre julho de 2007 a fevereiro de 2008. Foram inclusos pacientes de ambos os sexos, com idade maior que 18 anos e tempo de internação na UTI superior a 24 horas. Resultados: 144 (59%) pacientes foram do sexo masculino e 97 (41%) do sexo feminino. A idade média foi de 55 ± 17 anos, 85 (35%) pacientes tiveram sua admissão devido a pós-operatório de cirurgias eletivas, 33 (14%) devido a pós-operatório de cirurgias de urgência e 123 (51%) devido à intercorrências clínicas. A média de pontos do SAPS II foi de 28,7 ± 14,3. Conclusão: O modelo estudado não foi adequado para o uso nesta amostra de pacientes, sendo que o escore SAPS II apresentou uma discriminação regular e subestimou a letalidade hospitalar. Além disso, o estudo foi realizado em uma única UTI, o que mostra somente um determinado perfil de pacientes.

Introduction: The Simplified Acute Physiology Score (SAPS) is a model developed in France By Le Gall et al. in 1983, modified for SAPS II in 1993. It consists of 12 physiological variables, age, type of admission and presence of chronic disease. This study aims to analyze the prediction of mortality of SAPS II in patients admitted to the ICU of São José Hospital, Criciúma, SC. Methods: Prospective cohort study conducted from July 2007 to February 2008. We included patients of both sexes, older than 18years and duration of ICU stay longer than 24 hours. Results: 144 (59%) patients were male and 97 (41%) were female. The average age was 55 ± 17 years, 85 (35%) patients had their admission due to postoperative elective surgery, 33 (14%) due to postoperative emergency surgery and 123 (51%) due to clinical complications. The average score on the SAPS II was 28,7 ± 14,3. Conclusion: ICU scoring systems has become an important tool to measure the performance of the ICU and may be used for resource allocation, selection of patients, quality assurance. The model studied was not suitable for use in this sample of patients. The SAPS II score had a regular discrimination and underestimated the mortality rate. In addition, the study was conducted in a single ICU, which shows only a certain profile of patients.

The effects of N-acetylcysteine and deferoxamine on plasma cytokine and oxidative damage parameters in critically ill patients with prolonged hypotension: a randomized controlled trial.

Reactive oxygen species and inflammation have been implicated in renal tubule cell injury. However, there is some controversy concerning whether antioxidants might attenuate oxidative damage and inflammation in humans after hypotension in the setting of critical illness. This study was a prospective, randomized, double-blinded, placebo-controlled study that included patients with hypotension. Patients were randomized to receive either N-acetylcysteine (NAC; 50 mg/kg by 4 hours followed by 100 mg/kg/d for 48 hours diluted in 5% glucose) and deferoxamine (DFX; at a single dose of 1000 mg diluted in 5% glucose) or placebo. The primary study outcome was the serum levels of markers of oxidative damage and inflammatory response. Secondary outcomes included the incidence of acute renal failure, serum creatinine at hospital discharge, intensive care unit length of stay, and length of hospital stay. Thirty patients were enrolled in the study. The use of NAC plus DFX decreased the oxidative damage parameters but not plasma interleukin-6 levels. In contrast, plasma nitrite levels increased 24 hours after NAC plus DFX administration. On analysis of secondary outcomes, it was observed that creatinine levels at hospital discharge were lower in patients receiving NAC plus DFX when compared with placebo. NAC plus DFX administration was able to decrease plasma markers of oxidative damage and creatinine levels at hospital discharge.

Avaliação do estado nutricional e do perfil clínico-epidemiológico dos pacientes em tratamento hemodialítico no Hospital São José de Criciúma e na Nefroclínica-Criciúma / Evaluation of the nutrition state and clinical and epidemiológico profile of patients in hemodialysis at Hospital São José de Criciuma and Nefroclinica-Criciuma

Objetivos Avaliar estado nutricional e perfil clínico-epidemiológico dos pacientes em tratamento hemodialítico no Hospital São José de Criciúma e na NefroclínicaCriciúma. Metodologia Estudo transversal, com análise de prontuários, entrevista e exame físico. Realizada avaliação nutricional pelo método de Avaliação Nutricional Subjetiva Global (SGA). As seguintes variáveis foram avaliadas: ferritina, colesterol total, uréia, creatinina, hemoglobina, paratormônio, idade, sexo, cor, tempo de diálise, classe sócio-econômica (CSE), causa da insuficiência renal crônica (IRC), doença cardiovascular, hepatite B e C. A análise estatística foi realizada através do teste-t, trabalhando com um nível de confiabilidade de 95%. Resultados Foram avaliados 103 pacientes, sendo 37 do Hospital São José e 66 da Nefroclínica. As causas de IRC mais prevalentes foram diabetes melito (44,66%) e hipertensão arterial sistêmica (25,24%). Apresentavam estado nutricional adequado (SGA=1) 8,3% dos pacientes e risco nutricional/desnutrição leve (SGA=2), 90,5%. A prevalência de anemia foi de 46,6% e de hepatite B e C, 4,8% e 5,8%. A prevalência de hiperparatireoidismo foi de 36,8% e a de doença cardiovascular (DCV) foi de 31%. Risco nutricional esteve relacionado ao maior tempo de diálise (p=0,008) e a menores níveis de uréia (p=0,03). Observou-se prevalência de DCV duas vezes maior nos pacientes desnutridos (SGA=2). Não houve relação entre CSE e estado nutricional. Conclusão A maioria dos pacientes avaliados apresenta desnutrição leve ou risco de desnutrição, independente da classesócio-econômica. Observou-se que: a principal causa de IRC terminal nestes pacientes é o DM; os níveis séricos de uréia podem estar associados à desnutrição e pacientes mal nutridos estão mais propensos a complicações cardiovasculares.

Objectives assess nutritional status and clinical and epidemiological profile of patients on hemodialysis treatment at the Hospital Sao Jose de Criciuma and Nefroclínica-Criciúma. Methodology Study cross, with analysis of records, interview and physical examination. Held nutritional assessment by the method of Nutrition Assessment Subjective Global (SGA). The following variables were analyzed: ferritin, total cholesterol, urea, creatinine, hemoglobin, parathormone, age, sex, color, length of dialysis, socio-economic classes (SEC), cause of chronic renal failure (CRF), cardiovascular disease, hepatitis B and C. The statistical analysis was performed by t-test, working with a level of reliability of 95%. Results were evaluated 103 patients, and 37 of St. Joseph Hospital and 66 of Nefroclínica. The causes of CRF were more prevalent diabetes mellitus (44.66%) and hypertension (25.24%). Presented adequate nutritional status (SGA = 1) 8.3% of patients and nutritional risk / mild malnutrition (SGA = 2), 90.5%. The prevalence of anaemia was 46.6% and hepatitis B and C, 4.8% and 5.8%. The prevalence of hyperparathyroidism was 36.8% and of cardiovascular disease (CVD) was 31%. Risk nutrition was related to the longer time of dialysis (p = 0008) and lower levels of urea (p = 0.03). It was observed prevalence of CVD two times higher in patients malnourished (SGA = 2). There was no relationship between SEC and nutritional status. Conclusion The majority of patients presenting mild malnutrition or risk of malnutrition, regardless of socio-economic classes. It was observed that: the main cause of IRC terminal in these patients is the DM; serum levels of urea can be associated with malnutrition and poorly nourished patients are more prone to cardiovascular complications.

Efficacy of the combination of N-acetylcysteine and desferrioxamine in the prevention and treatment of gentamicin-induced acute renal failure in male Wistar rats.

BACKGROUND: Oxidative stress and the formation of aminoglycoside-iron complexes through iron-dependent Fenton reaction have been proposed to be the major mechanisms in the development of GM-induced acute renal failure (ARF); however, the efficacy of the combination of N-acetylcysteine (NAC) and desferrioxamine (DFX) in the prevention and the treatment of GM-induced ARF has not previously been investigated. METHODS: In the prevention protocol, adult male Wistar rats received gentamicin (GM) [70 mg/kg, intraperitoneally (i.p), each 12 h for 7 days], NAC (20 mg/kg, sc, each 8 h for 7 days) and/or DFX (20 mg/kg, sc, at first, fourth and seventh days). In the treatment protocol animals received GM for 7 days. Additionally, animals received NAC and or DFX starting in the fourth day after GM administration. Parameters of renal function had been evaluated 24 h, 4 and 8 days after the beginning of GM administration in the prevention protocol and in Days 5 and 8 in the treatment protocol. At the end of experiment, lipid peroxidation (TBARS assay) and protein oxidation (protein carbonyls levels) formation were evaluated in kidney tissue as oxidative damage parameters. RESULTS: In the prevention protocol, GM-induced ARF was prevented by the NAC and DFX association. Lipid peroxidation was attenuated by both antioxidant treatments, but the effects of NAC plus DFX were of greater magnitude. In the treatment protocol, plasma markers of renal injury were improved only in the NAC group, despite the similar antioxidant effect of both NAC, DFX and NAC plus DFX. CONCLUSION: Although the combination of NAC and DFX was more effective in the prevention protocol, the use of NAC alone seemed to be superior to NAC-DFX combination, in the treatment of GM-induced ARF in adult male Wistar rats.