Systemic oxidative stress is implicated in the pathogenesis of brain edema in rats with chronic liver failure.

Chronic liver failure leads to hyperammonemia, a central component in the pathogenesis of hepatic encephalopathy (HE); however, a correlation between blood ammonia levels and HE severity remains controversial. It is believed oxidative stress plays a role in modulating the effects of hyperammonemia. This study aimed to determine the relationship between chronic hyperammonemia, oxidative stress, and brain edema (BE) in two rat models of HE: portacaval anastomosis (PCA) and bile-duct ligation (BDL). Ammonia and reactive oxygen species (ROS) levels, BE, oxidant and antioxidant enzyme activities, as well as lipid peroxidation were assessed both systemically and centrally in these two different animal models. Then, the effects of allopurinol (xanthine oxidase inhibitor, 100mg/kg for 10days) on ROS and BE and the temporal resolution of ammonia, ROS, and BE were evaluated only in BDL rats. Similar arterial and cerebrospinal fluid ammonia levels were found in PCA and BDL rats, both significantly higher compared to their respective sham-operated controls (p<0.05). BE was detected in BDL rats (p<0.05) but not in PCA rats. Evidence of oxidative stress was found systemically but not centrally in BDL rats: increased levels of ROS, increased activity of xanthine oxidase (oxidant enzyme), enhanced oxidative modifications on lipids, as well as decreased antioxidant defense. In PCA rats, a preserved oxidant/antioxidant balance was demonstrated. Treatment with allopurinol in BDL rats attenuated both ROS and BE, suggesting systemic oxidative stress is implicated in the pathogenesis of BE. Analysis of ROS and ammonia temporal resolution in the plasma of BDL rats suggests systemic oxidative stress might be an important "first hit", which, followed by increases in ammonia, leads to BE in chronic liver failure. In conclusion, chronic hyperammonemia and oxidative stress in combination lead to the onset of BE in rats with chronic liver failure.

Correlacion entre lactato arterial y venoso central en niños con sepsis en estado critico

Este estudio fue conducido para evaluar la correlación entre lactato arterial y venoso central en niños con sepsis y choque séptico de una unidad de cuidado intensivo pediátrico. Se incluyeron 42 pacientes con edades comprendidas entre 1 mes y 17 años 364 días con diagnóstico de sepsis y choque séptico que ingresaron a la Unidad de Cuidado Intensivo en un hospital universitario de referencia. Se registró el valor del lactato obtenido de una muestra de sangre arterial y de sangre venosa central tomadas simultáneamente y dentro de las primeras 24 horas del ingreso a la unidad. Por medio de la prueba de Rho de Spearman se encontró una correlación de 0,872 (p<0,001) y se ajustó al uso de medicamentos, vasoactivos, edad y peso (modelo de regresión no paramétrico quantílico), manteniéndose una correlación fuerte y significativa.

High volume peritoneal dialysis for acute renal failure

Background. Peritoneal dialysis (PD) is still widely used for acute renal failure (ARF) in developing countries despite concerns about its inadequacy. Continuous PD has been evaluated in ARF by analyzing the resolution of metabolic abnormality and normalization of plasma pH, bicarbonate, and potassium.Methodology: A prospective study was performed on 30 ARF patients who were assigned to high-dose continuous PD (Kt/V = 0.65 per session) via a flexible catheter (Tenckhoff) and automated PD with a cycler. Fluid removal, pH and metabolic control, protein Loss, and patient outcome were evaluated.Results: Patients received 236 continuous PD sessions; 76% were admitted to ICUs. APACHE II score was 32.2 +/- 8.65. BUN concentrations stabilized after 3 sessions, creatinine after 4, and bicarbonate and pH after 2. Fluid removal was 2.1 +/- 0.62 L/day. Creatinine and urea clearances were 15.8 +/- 4.16 and 17.3 +/- 5.01 mL/minute respectively. Normalized creatinine clearance and urea Kt/V values were 110.6 +/- 22.5 L/week/1.73 m(2) body surface area and 3.8 +/- 0.6 respectively. Solute reduction index was 41% +/- 6.5% per session. Serum albumin values remained stable in spite of considerable protein tosses (median 21.7 g/day, interquartile range 9.1 - 29.8 g/day). Regarding ARF outcome, 23% of patients presented renal function recovery, 13% remained on dialysis after 30 days of follow-up, and 57% died.Conclusion: High-dose continuous PD by flexible catheter and cycler was an effective treatment for ARF. It provided high solute removal, allowing appropriate metabolic and pH control, and adequate dialysis dose and fluid removal. Continuous PD can therefore be considered an alternative to other forms of renal replacement therapy in ARF.

Acute renal failure: Clinical outcome and causes of death

Acute renal failure (ARF) is a frequent complication in hospitalized patients and is strongly related to increase in mortality. In order to analyze the clinical outcome and the prognostic factors in hospital-acquired ARF a prospective study was performed. Data from 200 patients with established ARF during the period of January 1987 through July 1990 were collected. The incidence of ARF was 4.9/1000 admissions. Renal ischemia (50%) and nephrotoxic drugs (21%) were the main etiologic factors. The histologic study done in 43 patients showed: acute tubular necrosis (53%), tubular hydropic degeneration (16%), glomerulopathies (16%), and other lesions (15%). Dialysis therapy was performed in 101 patients. The mortality rate was 46.5% and the most important causes of death were. sepsis (38%), respiratory failure (19%), and multiple organ failure (11%). Higher mortality was observed in oliguric patients (62.9%) than nonoliguric (34.5%) (p < 0.05) and in ischemic renal failure (56.7%) when compared to nephrotoxic renal failure (14.7%) (p < 0.05). As primary cause of death was not associated to the acute renal failure, conclude that acute renal failure is an important marker of the gravity of the underlying disease and not the cause of death.

Acute renal failure in renal allograft recipients and patients with native kidneys

In order to evaluate the role of underlying disease in the high mortality observed in acute renal failure (ARF) and risk factors related to the development of oliguric ARF in renal allograft recipients, two groups were selected: 34 patients with native kidneys, aged 16 and 57 years, and presenting ischemic ARF caused by cardiovascular collapse, with no signs of infection at the time of diagnosis; and 34 renal allograft recipients who developed ARF immediately after transplantation, without rejection. ARF was defined either as 30% increase of basal plasmatic creatinine in patients with native kidneys or non-normalization of plasmatic creatinine at day 5 after transplantation in renal allograft recipients; oliguria as diuresis ≤ 400 mL/24 h. There were no differences in age, male frequency, oliguria presence and duration, need for dialysis, and infection episodes for renal allograft recipients and patients with native kidneys. The development of sepsis (3% and 41%) and death rate (3% and 44%) were higher in patients with native kidneys (p < 0.01). The renal allograft recipients with both oliguric (n = 18) and nonoliguric (n = 16) ARF were evaluated and no difference was observed in the recipient's age, donor's age, cold ischemia time, time elapsed until plasmatic creatinine normalization, donor's plasmatic creatinine or urea, and mean arterial pressure. No differences were observed between the groups regarding frequency of infection episodes during ARF and frequency of death. In conclusion, renal allograft recipients presented a lower death rate and were less susceptible to sepsis. Cold ischemia time, age, and hemodynamic characteristics of the donor did not affect the development of oliguria.

Peritoneal dialysis in acute renal failure

The definition of adequate dialysis in acute renal failure (ARF) is complex and involves the time of referral to dialysis, dose, and dialytic method. Nephrologist experience with a specific procedure and the availability of different dialysis modalities play an important role in these choices. There is no consensus in literature on the best method or ideal dialysis dose in ARF. Peritoneal dialysis (PD) is used less and less in ARF patients, and is being replaced by continuous venovenous therapies. However, it should not be discarded as a worthless therapeutic option for ARF patients. PD offers several advantages over hemodialysis, such as its technical simplicity, excellent cardiovascular tolerance, absence of an extracorporeal circuit, lack of bleeding risk, and low risk of hydro-electrolyte imbalance. PD also has some limitations, though: it needs an intact peritoneal cavity, carries risks of peritoneal infection and protein losses, and has an overall lower effectiveness. Because daily solute clearance is lower with PD than with daily HD, there have been concerns that PD cannot control uremia in ARF patients. Controversies exist concerning its use in patients with severe hypercatabolism; in these cases, daily hemodialysis or continuous venovenous therapy have been preferred. There is little literature on PD in ARF patients, and what exists does not address fundamental parameters such as adequate quantification of dialysis and patient catabolism. Given these limitations, there is a pressing need to re-evaluate the adequacy of PD in ARF using accepted standards. Therefore, new studies should be undertaken to resolve these problems. Copyright © Informa Healthcare.

Postmortem diagnosis of acute myocardial infarction in patients with acute respiratory failure - demographics, etiologic and pulmonary histologic analysis

OBJECTIVES: Acute respiratory failure is present in 5% of patients with acute myocardial infarction and is responsible for 20% to 30% of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life. METHODS: This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression. RESULTS: In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in 11.9% of patients, systemic arterial hypertension in 10.1% and dilated cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema. CONCLUSIONS: For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5% were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has not previously been reported.

Summary of the II Brazilian Guideline Update on Acute Heart Failure 2009/2011

In the past two years we observed several changes in the diagnostic and therapeutic approach of patients with acute heart failure (acute HF), which led us to the need of performing a summary update of the II Brazilian Guidelines on Acute Heart Failure 2009. In the diagnostic evaluation, the diagnostic flowchart was simplified and the role of clinical assessment and echocardiography was enhanced. In the clinical-hemodynamic evaluation on admission, the hemodynamic echocardiography gained prominence as an aid to define this condition in patients with acute HF in the emergency room. In the prognostic evaluation, the role of biomarkers was better established and the criteria and prognostic value of the cardiorenal syndrome was better defined. The therapeutic approach flowcharts were revised, and are now simpler and more objective. Among the advances in drug therapy, the safety and importance of the maintenance or introduction of beta-blockers in the admission treatment are highlighted. Anticoagulation, according to new evidence, gained a wider range of indications. The presentation hemodynamic models of acute pulmonary edema were well established, with their different therapeutic approaches, as well as new levels of indication and evidence. In the surgical treatment of acute HF, CABG, the approach to mechanical lesions and heart transplantation were reviewed and updated. This update strengthens the II Brazilian Guidelines on Acute Heart Failure to keep it updated and refreshed. All clinical cardiologists who deal with patients with acute HF will find, in the guidelines and its summary, important tools to help them with the clinical practice for better diagnosis and treatment of their patients.

Noninvasive ventilation immediately after extubation improves weaning outcome after acute respiratory failure: a randomized controlled trial

Abstract Introduction Noninvasive ventilation (NIV), as a weaning-facilitating strategy in predominantly chronic obstructive pulmonary disease (COPD) mechanically ventilated patients, is associated with reduced ventilator-associated pneumonia, total duration of mechanical ventilation, length of intensive care unit (ICU) and hospital stay, and mortality. However, this benefit after planned extubation in patients with acute respiratory failure of various etiologies remains to be elucidated. The aim of this study was to determine the efficacy of NIV applied immediately after planned extubation in contrast to oxygen mask (OM) in patients with acute respiratory failure (ARF). Methods A randomized, prospective, controlled, unblinded clinical study in a single center of a 24-bed adult general ICU in a university hospital was carried out in a 12-month period. Included patients met extubation criteria with at least 72 hours of mechanical ventilation due to acute respiratory failure, after following the ICU weaning protocol. Patients were randomized immediately before elective extubation, being randomly allocated to one of the study groups: NIV or OM. We compared both groups regarding gas exchange 15 minutes, 2 hours, and 24 hours after extubation, reintubation rate after 48 hours, duration of mechanical ventilation, ICU length of stay, and hospital mortality. Results Forty patients were randomized to receive NIV (20 patients) or OM (20 patients) after the following extubation criteria were met: pressure support (PSV) of 7 cm H2O, positive end-expiratory pressure (PEEP) of 5 cm H2O, oxygen inspiratory fraction (FiO2) ≤ 40%, arterial oxygen saturation (SaO2) ≥ 90%, and ratio of respiratory rate and tidal volume in liters (f/TV) < 105. Comparing the 20 patients (NIV) with the 18 patients (OM) that finished the study 48 hours after extubation, the rate of reintubation in NIV group was 5% and 39% in OM group (P = 0.016). Relative risk for reintubation was 0.13 (CI = 0.017 to 0.946). Absolute risk reduction for reintubation showed a decrease of 33.9%, and analysis of the number needed to treat was three. No difference was found in the length of ICU stay (P = 0.681). Hospital mortality was zero in NIV group and 22.2% in OM group (P = 0.041). Conclusions In this study population, NIV prevented 48 hours reintubation if applied immediately after elective extubation in patients with more than 3 days of ARF when compared with the OM group. Trial Registration number ISRCTN: 41524441.

Postmortem diagnosis of acute myocardial infarction in patients with acute respiratory failure: demographics, etiologic and pulmonary histologic analysis

OBJECTIVES: Acute respiratory failure is present in 5% of patients with acute myocardial infarction and is responsible for 20% to 30% of the fatal post-acute myocardial infarction. The role of inflammation associated with pulmonary edema as a cause of acute respiratory failure post-acute myocardial infarction remains to be determined. We aimed to describe the demographics, etiologic data and histological pulmonary findings obtained through autopsies of patients who died during the period from 1990 to 2008 due to acute respiratory failure with no diagnosis of acute myocardial infarction during life. METHODS: This study considers 4,223 autopsies of patients who died of acute respiratory failure that was not preceded by any particular diagnosis while they were alive. The diagnosis of acute myocardial infarction was given in 218 (4.63%) patients. The age, sex and major associated diseases were recorded for each patient. Pulmonary histopathology was categorized as follows: diffuse alveolar damage, pulmonary edema, alveolar hemorrhage and lymphoplasmacytic interstitial pneumonia. The odds ratio of acute myocardial infarction associated with specific histopathology was determined by logistic regression. RESULTS: In total, 147 men were included in the study. The mean age at the time of death was 64 years. Pulmonary histopathology revealed pulmonary edema as well as the presence of diffuse alveolar damage in 72.9% of patients. Bacterial bronchopneumonia was present in 11.9% of patients, systemic arterial hypertension in 10.1% and dilated cardiomyopathy in 6.9%. A multivariate analysis demonstrated a significant positive association between acute myocardial infarction with diffuse alveolar damage and pulmonary edema. CONCLUSIONS: For the first time, we demonstrated that in autopsies of patients with acute respiratory failure as the cause of death, 5% were diagnosed with acute myocardial infarction. Pulmonary histology revealed a significant inflammatory response, which has not previously been reported.

Usefulness of a clinical diagnosis of ICU-acquired paresis to predict outcome in patients with SIRS and acute respiratory failure

Neuromuscular abnormalities are common in ICU patients. We aimed to assess the incidence of clinically diagnosed ICU-acquired paresis (ICUAP) and its impact on outcome.

Measurement issues in trials of pediatric acute diarrheal diseases: a systematic review

BACKGROUND: Worldwide, diarrheal diseases rank second among conditions that afflict children. Despite the disease burden, there is limited consensus on how to define and measure pediatric acute diarrhea in trials. OBJECTIVES: In RCTs of children involving acute diarrhea as the primary outcome, we documented (1) how acute diarrhea and its resolution were defined, (2) all primary outcomes, (3) the psychometric properties of instruments used to measure acute diarrhea and (4) the methodologic quality of included trials, as reported. METHODS: We searched CENTRAL, Embase, Global Health, and Medline from inception to February 2009. English-language RCTs of children younger than 19 years that measured acute diarrhea as a primary outcome were chosen. RESULTS: We identified 138 RCTs reporting on 1 or more primary outcomes related to pediatric acute diarrhea/diseases. Included trials used 64 unique definitions of diarrhea, 69 unique definitions of diarrhea resolution, and 46 unique primary outcomes. The majority of included trials evaluated short-term clinical disease activity (incidence and duration of diarrhea), laboratory outcomes, or a composite of these end points. Thirty-two trials used instruments (eg, single and multidomain scoring systems) to support assessment of disease activity. Of these, 3 trials stated that their instrument was valid; however, none of the trials (or their citations) reported evidence of this validity. The overall methodologic quality of included trials was good. CONCLUSIONS: Even in what would be considered methodologically sound clinical trials, definitions of diarrhea, primary outcomes, and instruments employed in RCTs of pediatric acute diarrhea are heterogeneous, lack evidence of validity, and focus on indices that may not be important to participants.

Role of TRAIL and the pro-apoptotic Bcl-2 homolog Bim in acetaminophen-induced liver damage

Acetaminophen (N-acetyl-para-aminophenol (APAP), paracetamol) is a commonly used analgesic and antipyretic agent. Although considered safe at therapeutic doses, accidental or intentional overdose causes acute liver failure characterized by centrilobular hepatic necrosis with high morbidity and mortality. Although many molecular aspects of APAP-induced cell death have been described, no conclusive mechanism has been proposed. We recently identified TNF-related apoptosis-inducing ligand (TRAIL) and c-Jun kinase (JNK)-dependent activation of the pro-apoptotic Bcl-2 homolog Bim as an important apoptosis amplification pathway in hepatocytes. In this study, we, thus, investigated the role of TRAIL, c-JNK and Bim in APAP-induced liver damage. Our results demonstrate that TRAIL strongly synergizes with APAP in inducing cell death in hepatocyte-like cells lines and primary hepatocyte. Furthermore, we found that APAP strongly induces the expression of Bim in a c-JNK-dependent manner. Consequently, TRAIL- or Bim-deficient mice were substantially protected from APAP-induced liver damage. This study identifies the TRAIL-JNK-Bim axis as a novel target in the treatment of APAP-induced liver damage and substantiates its general role in hepatocyte death.