Figen Esen

Effect of magnesium sulfate administration on blood-brain barrier in a rat model of intraperitoneal sepsis: a randomized controlled experimental study.

IntroductionPermeability changes in the blood–brain barrier (BBB) and their possible contribution to brain edema formation have a crucial role in the pathophysiology of septic encephalopathy. Magnesium sulfate has been shown to have a protective effect on BBB integrity in multiple experimental models. In this study we determine whether magnesium sulfate administration could have any protective effects on BBB derangement in a rat model of sepsis.MethodsThis randomized controlled experimental study was performed on adult male Sprague–Dawley rats. Intraperitoneal sepsis was induced by using the infected fibrin–thrombin clot model. To examine the effect of magnesium in septic and sham-operated rats, a dose of 750 μmol/kg magnesium sulfate was given intramuscularly immediately after surgery. Control groups for both infected and sham-operated rats were injected with equal volume of saline. Those rats surviving for 24 hours were anesthetized and decapitated for the investigation of brain tissue specific gravity and BBB integrity by the spectrophotometric assay of Evans blue dye extravasations. Another set of experiments was performed for hemodynamic measurements and plasma magnesium level analysis. Rats were allocated into four parallel groups undergoing identical procedures.ResultsSepsis significantly increased BBB permeability to Evans blue. The dye content of each hemisphere was significantly lower in the magnesium-treated septic rats (left hemisphere, 0.00218 ± 0.0005; right hemisphere, 0.00199 ± 0.0007 [all results are means ± standard deviation]) than in control septic animals (left hemisphere, 0.00466 ± 0.0002; right hemisphere, 0.00641 ± 0.0003). In septic animals treated with magnesium sulfate, specific gravity was higher (left hemisphere, 1.0438 ± 0.0007; right hemisphere, 1.0439 ± 0.0004) than in the untreated septic animals (left hemisphere, 1.0429 ± 0.0009; right hemisphere, 1.0424 ± 0.0012), indicating less edema formation with the administration of magnesium. A significant decrease in plasma magnesium levels was observed 24 hours after the induction of sepsis. The dose of magnesium that we used maintained the baseline plasma magnesium levels in magnesium-treated septic rats.ConclusionsMagnesium administration attenuated the increased BBB permeability defect and caused a reduction in brain edema formation in our rat model of intraperitoneal sepsis.

Effects of sustained inflation and postinflation positive end- expiratory pressure in acute respiratory distress syndrome: Focusing on pulmonary and extrapulmonary forms*

ObjectiveTo investigate whether the response to sustained inflation and postinflation positive end-expiratory pressure varies between acute respiratory distress syndrome with pulmonary (ARDSp) and extrapulmonary origin (ARDSexp). DesignProspective clinical study. SettingMultidisciplinary intensive care unit in a university hospital. PatientsA total of 11 patients with ARDSp and 13 patients with ARDSexp. InterventionsA 7 ml/kg tidal volume, 12–15 breaths/min respiratory rate, and an inspiratory/expiratory ratio of 1:2 was used during baseline ventilation. Positive end-expiratory pressure levels were set according to the decision of the primary physician. Sustained inflation was performed by 45 cm H2O continuous positive airway pressure for 30 secs. Postinflation positive end-expiratory pressure was titrated decrementally, starting from a level of 20 cm H2O to keep the peripheral oxygen saturation between 92% and 95%. Fio2 was decreased, and baseline tidal volume, respiratory rate, inspiratory/expiratory ratio were maintained unchanged throughout the study period. Measurements and Main ResultsBlood gas, airway pressure, and hemodynamic measurements were performed at the following time points: at baseline and at 15 mins, 1 hr, 4 hrs, and 6 hrs after sustained inflation. After sustained inflation, the Pao2/Fio2 ratio improved in all of the patients both in ARDSp and ARDSexp. However, the Pao2/Fio2 ratio increased to >200 in four ARDSp patients (36%) and in seven ARDSexp patients (54%). In two of those ARDSp patients, the Pao2/Fio2 ratio was found to be <200, whereas none of the ARDSexp patients revealed Pao2/Fio2 ratios of <200 at the 6-hr measurement. Postinflation positive end-expiratory pressure levels were set at 16.7 ± 2.3 cm H2O in ARDSexp and 15.6 ± 2.5 cm H2O in ARDSp. The change in Pao2/Fio2 ratios was found statistically significant in patients with ARDSexp (p = .0001) and with ARDSp (p = .008). Respiratory system compliance increased in ARDSexp patients (p = .02), whereas the change in ARDSp was not statistically significant. ConclusionsSustained inflation followed by high levels of postinflation positive end-expiratory pressure provided an increase in respiratory system compliance in ARDSexp; however, arterial oxygenation improved in both ARDS forms.

Effects of magnesium administration on brain edema and blood-brain barrier breakdown after experimental traumatic brain injury in rats.

In this study, we examined the effects of magnesium sulfate administration on brain edema and blood–brain barrier breakdown after experimental traumatic brain injury in rats. Seventy-one adult male Sprague-Dawley rats were anesthetized, and experimental closed head trauma was induced by allowing a 450-g weight to fall from a 2-m height onto a metallic disk fixed to the intact skull. Sixty-eight surviving rats were randomly assigned to receive an intraperitoneal bolus of either 750 &mgr;mol/kg magnesium sulfate (group 4; n = 30) or 1 mL of saline (group 2; n = 30) 30 minutes after induction of traumatic brain injury; 39 nontraumatized animals received saline (group 1; n = 21) or magnesium sulfate (group 3; n = 18) with an identical protocol of administration. Brain water content and brain tissue specific gravity, as indicators of brain edema, were measured 24 hours after traumatic brain injury. Blood–brain barrier integrity was evaluated quantitatively 24 hours after injury by spectrophotometric assay of Evans blue dye extravasations. In the magnesium-treated injured group, brain water content was significantly reduced (left hemisphere: group 2, 83.2 ± 0.8; group 4, 78.4 ± 0.7 [P < .05]; right hemisphere: group 2, 83.1 ± 0.7; group 4, 78.4 ± 0.5. [P < .05]) and brain tissue specific gravity was significantly increased (left hemisphere: group 2, 1.0391 ± 0.0008; group 4, 1.0437 ± 0.001 [P < .05]; right hemisphere, group 2, 1.0384 ± 0.001; group 4, 1.0442 ± 0.005 [P < .05]) compared with the saline-treated injured group. Evans blue dye content in the brain tissue was significantly decreased in the magnesium-treated injured group (left hemisphere: group 2, 0.0204 ± 0.03; group 4, 0.0013 ± 0.0002 [P < .05]; right hemisphere: group 2, 0.0064 ± 0.0009; group 4, 0.0013 ± 0.0003 [P < .05]) compared with the saline-treated injured group. The findings of the present study support that beneficial effects of magnesium sulfate exist after severe traumatic brain injury in rats. These results also indicate that a blood–brain barrier permeability defect occurs after this model of diffuse traumatic brain injury, and magnesium seems to attenuate this defect.

Intravenous immunoglobulins prevent the breakdown of the blood-brain barrier in experimentally induced sepsis

Interventions:The effects of immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M on blood-brain barrier integrity and survival rates in septic rats were comparatively investigated. Measurements:Sepsis was induced by cecal ligation and perforation in Sprague-Dawley rats. The animals were divided into the following groups: Sham, cecal ligation and perforation, cecal ligation and perforation plus immunoglobulin G (250 mg/kg, intravenous), and cecal ligation and perforation plus immunoglobulins enriched with immunoglobulin A and immunoglobulin M (250 mg/kg, intravenous). Immunoglobulins were administered 5 mins before cecal ligation and perforation and the animals were observed for behavioral changes for 24 hrs following cecal ligation and perforation. Blood-brain barrier permeability was functionally and structurally evaluated by determining the extravasation of Evans Blue and horseradish peroxidase tracers, respectively. Immunohistochemistry and Western blotting for occludin were performed. Main Results:The high mortality rate (34%) noted in the septic rats was decreased to 15% and 3% by immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M, respectively (p < .01). Both immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M alleviated the symptoms of sickness behavior in the septic rats, with the animals becoming healthy and active. Increased extravasation of Evans Blue into the brain tissue of the septic rats was markedly decreased with the administration of both immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M (p < .01). Occludin expression remained essentially unchanged in all groups, including the cecal ligation and perforation group. In the cecal ligation and perforation group, increased luminal and abluminal vesicles containing electron-dense horseradish peroxidase-reaction product were noted in the cytoplasm of endothelial cells located in the hippocampus and the cerebral cortex. Tight junction was ultrastructurally intact, suggesting that the transcellular pathway is responsible for the blood-brain barrier breakdown in sepsis. Following immunoglobulin G or immunoglobulins enriched with immunoglobulin A and immunoglobulin M treatment, no ultrastructural evidence of leaky capillaries in the brain was observed in the septic rats, indicating the blockade of the transcellular pathway by immunoglobulins administration. Conclusions:Our study suggests that immunoglobulin G and immunoglobulins enriched with immunoglobulin A and immunoglobulin M improve the integrity of the blood-brain barrier and inhibits cecal ligation and perforation-induced symptoms of sickness behavior in rats. (Crit Care Med 2012; 40:–1220)

Comparison of pressure- and flow-triggered pressure-support ventilation on weaning parameters in patients recovering from acute respiratory failure.

ConclusionThe application of pressure- or flow-triggered PSV with Servo 300 ventilator does not make significant changes, in the short-term, on gas exchange, respiratory mechanics and inspiratory work-load in non-COPD patients recovering from acute respiratory failure.

The treatment of acute liver failure with fractionated plasma separation and adsorption system: Experience in 85 applications.

Introduction: Artificial liver support systems represent a potential useful option for the treatment of liver failure. The outcomes of patients treated with the fractionated plasma separation and adsorption (FPSA) system are presented. Patients and methods: FPSA was performed 85 times for 27 patients (median 3 treatments/patient) with liver failure [85.2% acute liver failure (ALF) and 14.8% acute‐on‐chronic liver failure] using the Prometheus 4008H (Fresenius Medical Care) unit. Citrate was used for anticoagulation. A variety of clinical and biochemical parameters were assessed. Comparisons between pretreatment and post‐treatment data were performed using paired t‐test. Results: The 85 sessions had a mean duration of 6 h. There were significant decreases in total bilirubin (13.18 ± 9.46 mg/dL vs. 9.76 ± 7.05 mg/dL; P < 0.0001), ammonia (167.6 ± 75 mg/dL vs. 120 ± 43.8 mg/dL; P < 0.0001), blood urea nitrogen (BUN; 12.55 ± 13.03 mg/dL vs. 8.18 ± 8.15 mg/dL; P < 0.0001), creatinine (0.54 ± 0.47 mg/dL vs. 0.46 ± 0.37 mg/dL; P = 0.0022) levels, and in pH (7.48 ± 0.05 vs. 7.44 ± 0.08; P = 0.0045). Four patients (14.8%) received liver transplantation after the treatments; in nine patients, transplantation was not necessary anymore (33%); the remaining 14 patients did not receive a transplantation because they were either not appropriate candidates or no organ was available. Overall survival was 48.1% (4 transplanted and 9 treated patients). No hematological complications related to FPSA were observed. Conclusions: FPSA system is a safe and effective detoxification method for patients with liver dysfunction, including ALF. The system is useful as a symptomatic treatment before liver transplantation; in up to 1/3 of the cases, it can even be used as a sole method of treatment. J. Clin. Apheresis 25:195–201, 2010.

Risk Factors for Mortality of Nosocomial Bacteraemia in Intensive Care Units

Objective: The aim of this study was to follow critically ill patients prospectively in intensive care units (ICUs) to determine risk factors for mortality and outcome associated with nosocomial bacteraemia (NB). Subjects and Methods: A case-control study of 176 patients was conducted to identify the risk factors for mortality of NB in ICU patients. The study was performed in emergency, surgical and general surgical ICUs with 23 beds during a 15-month period. A total of 1,450 patients were admitted to the ICUs during the study period. The USA Center for Disease Control and Prevention definitions were used to diagnose nosocomial infections. Nosocomial bacteraemia was defined as the isolation of one or more organisms from blood cultures taken at least 48 h after admission, which were not related to a problem present on admission. An assessment of whether the isolated organisms represented true bacteraemia rather than contamination was made by clinical or laboratory evidence of infection. Results: A total of 214 bacteraemia episodes were found in the 176 patients (64 female, 112 male; 51.3 ± 21.3 years old), 90 of whom died and 86 survived. The bacteraemia rate was 12.1%. The most common etiological agents of bacteraemia were Klebsiella pneumoniae: 46 (21.5%), methicillin-resistant Staphylococcus aureus: 46 (21.5%), Pseudomonas aeruginosa: 32 (14.9%), and Escherichia coli: 20 (9.3%). Multivariate analysis showed that the requirement of mechanical ventilation for more than 7 days (p < 0.001), total parenteral nutrition (p = 0.034), inotropic drug (p < 0.001), and increased creatinine level (p = 0.034) were independent risk factors for mortality of NB in ICUs. Conclusions: Nosocomial infections caused by Gram-negative bacteria continue to be one of the major sources of morbidity and mortality.

Respiratory and haemodynamic effects of conventional volume controlled PEEP ventilation, pressure regulated volume controlled ventilation and low frequency positive pressure ventilation with extracorporeal carbon dioxide removal in pigs with acute ARDS

The purpose of this study was to evaluate whether any benefit of low frequency positive pressure ventilation with extracorporeal carbon dioxide removal (LFPPV–ECCO2R) existed over either volume controlled ventilation (VCV) with measured best–PEEP or pressure regulated volume controlled ventilation (PRVCV) with an inspiration/expiration (I/E) ratio of 4:1, with respect to arterial oxygenation, lung mechanics and haemodynamics, in acute respiratory failure.

Effects of Volume Controlled Ventilation with Peep, Pressure Regulated Volume Controlled Ventilation and Low Frequency Positive Pressure Ventilation with Extracorporeal Carbon Dioxide Removal on Total Static Lung Compliance and Oxygenation in Pigs with ARDS

Adult respiratory distress syndrome (ARDS) is characterised by decreased lung compliance and functional residual capacity (FRC) and increased intrapulmonary shunting resulting in hypoxemia. The immediate treatment of this critical situation is respiratory therapy of one form or the other and various modes have been recommended since the description of the disease. Positive end expiratory pressure (PEEP) with large tidal volume (VT), which recruits atelectatic areas and increases FRC, was once suggested as the treatment of ARDS.1-6 However, this mode of ventilation may cause barotrauma and/or morphological changes due to high peak inspiratory pressures (PIP).

Comparison of Gastric Intramucosal pH Measurements with Oxygen Supply, Oxygen Consumption and Arterial Lactate in Patients with Severe Sepsis

Tissue hypoxia caused by the imbalance between the oxygen demand and the oxygen uptake, is considered to be the most important factor to the mortality and morbidity in patients with severe sepsis. However, the assessment of tissue oxygenation is still contraversial, since direct measurement of the adequacy of tissue oxygenation has not yet been available in the clinical setting.