Lütfi Telci

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.

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.

Comparison of the effects of sodium nitroprusside and isoflurane during rewarming on cardiopulmonary bypass

OBJECTIVES Afterdrop in core temperatures after discontinuation of cardiopulmonary bypass (CPB) is reported to be a sign of inadequate total body rewarming on CPB. The purpose of this study was to compare the effects of three different drug regimens on hemodynamic stability and the uniformity of rewarming during the rewarming period of CPB. DESIGN This prospective randomized study was performed in the Anesthesiology Department of the University of Istanbul. PARTICIPANTS Sixty-six patients undergoing uncomplicated valve replacement and aortocoronary bypass grafting surgery were studied. INTERVENTIONS Anesthesia was maintained with isoflurane and fentanyl infusion during the prebypass and the postbypass periods. Patients were allocated into three groups by the initiation of CPB. Group 1 (n = 22): fentanyl infusion + diazepam + sodium nitroprusside (SNP) in the rewarming period), group 2 (n = 22): fentanyl infusion + isoflurane, group 3, control (n = 22): fentanyl infusion + diazepam. Rectal, esophageal, and forearm temperatures were monitored throughout the study. MEASUREMENTS AND MAIN RESULTS None of the durational and temperature data showed significant differences between groups 1 and 2. In the control group, afterdrop in esophageal temperature was significantly higher than groups 1 and 2 (group 1: -1.4 +/- 0.9 degrees C, group 2: -1.44 +/- 0.8 degrees C, group 3: -2.1 +/- 0.65 degrees C). In group 1, the number of patients whose mean arterial pressure (MAP) decreased below 45 mmHg was significantly higher than group 2 (p = 0.002). Mean SNP infusion rate and mean isoflurane concentration during the rewarming period were calculated as 1.55 +/- 0.8 micrograms/kg/min and 0.775 +/- 0.27%, respectively. CONCLUSIONS Isoflurane produced more stable hemodynamic conditions than SNP during the rewarming period, improved the uniformity of rewarming, and permitted earlier extubation in the intensive care unit (ICU). It is concluded that isoflurane alone is capable of fulfilling the anesthesia needs during hypothermia and the rewarming period of CPB.

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.

The effects of airway pressure and inspiratory time on bacterial translocation.

BACKGROUND: Mechanical ventilation with high peak inspiratory pressure (PIP) induces lung injury and bacterial translocation from the lung into the systemic circulation. We investigated the effects of increased inspiratory time on translocation of intratracheally inoculated bacteria during mechanical ventilation with and without extrinsic positive end-expiratory pressure (PEEP). METHODS: Rats were ventilated in pressure-controlled mode with 14 cm H2O PIP, 0 cm H2O PEEP, I:E ratio 1/2, and Fio2 1.0. Subsequently, 0.5 mL of 105 cfu/mL Pseudomonas aeruginosa was inoculated through tracheostomy and rats were randomly assigned to six groups; two low-pressure groups (LP)1/2, 14 cm H2O PIP, 0 cm H2O PEEP, I:E = 1/2, and LP2/1 14 cm H2O PIP, 0 cm H2O PEEP, I:E = 2/1; two high-pressure groups (HP)1/2, 30 cm H2O PIP, 0 cm H2O PEEP, I:E = 1/2, and HP2/1, 30 cm H2O PIP, 0 cm H2O PEEP, I:E = 2/1; two HP PEEP groups (HPP)1/2, 30 cm H2O PIP, 10 cm H2O PEEP, I:E = 1/2, and HPP2/1, 30 cm H2O PIP, 10 cm H2O PEEP, I:E = 2/1. Blood cultures were obtained every 30 min. The rats were killed and their lungs were processed. RESULTS: When compared with baseline values, Pao2 decreased in the LP1/2, LP2/1, HP1/2, and HP2/1 groups at the last time point, but the decline in Pao2 reached statistical significance in only the HP1/2 group. The bacterial translocation rate was greater in group HPP2/1 than group HPP1/2 (P = 0.01). CONCLUSIONS: We found that high PIP, with or without prolonged inspiratory time, increased the rate of bacterial dissemination. PEEP prevented bacterial translocation in the high PIP group. However, the protective effect of PEEP was lost when inspiratory time was prolonged.