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.

Effects of adjunct treatment with intravenous immunoglobulins on the course of severe COVID-19: results from a retrospective cohort study.

OBJECTIVES: To evaluate the effect of adjunct treatment with Octagam, an intravenous immunoglobulin (IVIG) product, on clinical outcomes and biomarkers in critically ill COVID-19 patients. METHODS: Data from a single center was analyzed retrospectively. Patients had received preliminary standard intensive care (SIC) according to a local treatment algorithm, either alone or along with IVIG 5% at 30 g/day for 5 days. The two groups were compared regarding baseline characteristics, survival and changes in inflammation markers. Imbalance in baseline APACHE II scores was addressed by propensity score matching. Otherwise, Kaplan-Meier and multiple logistic regression models were used. RESULTS: Out of 93 patients, 51 had received IVIG and 42 had not. About 75% of patients were male and both groups had comparable body mass index and AB0 blood type distribution. IVIG-treated patients were younger (mean 65 ± 15 versus 71 ± 15 years, p = .066) and had slightly lower baseline disease scores (APACHE II: 20.6 versus 22.4, p = .281; SOFA: 5.0 versus 7.0, p = .006). Overall survival was 61% in the SIC + IVIG and 38% in the SIC only group (odds ratio: 2.2, 95% confidence interval: 0.9-5.4, p = .091 after controlling for baseline imbalances). IVIG significantly prolonged median survival time (68 versus 18 days, p = .014) and significantly reduced plasma levels of C-reactive protein (median change from baseline -71.5 versus -0.3 mg/L, p = .049). CONCLUSION: Clinically relevant benefits through adjunct IVIG treatment in COVID-19 need to be confirmed in a randomized, controlled trial.

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.

Effects of body temperature on ventilator-induced lung injury.

PURPOSE: To evaluate the effects of body temperature on ventilator-induced lung injury. MATERIAL AND METHODS: Thirty-four male Sprague-Dawley rats were randomized into 6 groups based on their body temperature (normothermia, 37 +/- 1 degrees C; hypothermia, 31 +/- 1 degrees C; hyperthermia, 41 +/- 1 degrees C). Ventilator-induced lung injury was achieved by ventilating for 1 hour with pressure-controlled ventilation mode set at peak inspiratory pressure (PIP) of 30 cmH2O (high pressure, or HP) and positive end-expiratory pressure (PEEP) of 0 cmH2O. In control subjects, PIP was set at 14 cmH2O (low pressure, or LP) and PEEP set at 0 cmH2O. Systemic chemokine and cytokine (tumor necrosis factor alpha , interleukin 1 beta , interleukin 6, and monocyte chemoattractant protein 1) levels were measured. The lungs were assessed for histological changes. RESULTS: Serum chemokines and cytokines were significantly elevated in the hyperthermia HP group compared with all 3 groups, LP (control), normothermia HP, and hypothermia HP. Oxygenation was better but not statistically significant in hypothermia HP compared with other HP groups. Cumulative mean histology scores were higher in hyperthermia HP and normothermia HP groups compared with control and normothermia HP groups. CONCLUSIONS: Concomitant hyperthermia increased systemic inflammatory response during HP ventilation. Although hypothermia decreased local inflammation in the lung, it did not completely attenuate systemic inflammatory response associated with HP ventilation.

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

OBJECTIVE: To investigate whether the response to sustained inflation and postinflation positive end-expiratory pressure varies between acute respiratory distress syndrome with pulmonary (ARDS(exp)) and extrapulmonary origin (ARDS(exp)). DESIGN: Prospective clinical study. SETTING: Multidisciplinary intensive care unit in a university hospital. PATIENTS: A total of 11 patients with ARDS and 13 patients with ARDS. INTERVENTIONS: A 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 RESULTS: Blood 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 ARDS(p) and ARDS(exp). However, the Pao2/Fio2 ratio increased to >200 in four ARDS(p) patients (36%) and in seven ARDS(p) patients (54%). In two of those ARDS patients, the Pao2/Fio2 ratio was found to be <200, whereas none of the ARDS(p) 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 H O in ARDS(p) and 15.6 +/- 2.5 cm H2O in ARDS. The change in Pao /Fio ratios was found statistically significant in patients with ARDS(p) (p =.0001) and with ARDS(p) (p =.008). Respiratory system compliance increased in ARDS patients (p =.02), whereas the change in ARDS was not statistically significant. CONCLUSIONS: Sustained inflation followed by high levels of postinflation positive end-expiratory pressure provided an increase in respiratory system compliance in ARDS; however, arterial oxygenation improved in both ARDS forms.

[The effects of immunonutrition on the development of nosocomial infections and on clinical outcome in critically ill patients]. / Yogun bakim hastalarinda uygulanan immünonütrisyonun nozokomiyal enfeksiyon gelisimine ve klinik sonuca etkisi.

BACKGROUND: We investigated the effects of early immunonutrition on the development of nosocomial infections and clinical outcome in intensive care patients. METHODS: Thirty mechanically ventilated patients were randomly assigned to two enteral nutrition regimens in the intensive care unit. Fifteen patients (8 males, 7 females; mean age 54 years; range 21 to 72 years) received immunonutrition solution containing arginine, nucleotides, and polyunsaturated fatty acids, while controls (10 males, 5 females; mean age 55 years; range 24 to 78 years) received isocaloric solution. The patients were evaluated daily using the APACHE II and SOFA (Simplified Organ Failure Assessment) scoring systems. Infections were sought in tracheal, blood, urine, and catheter cultures. Changes in nitrogen balance, leukocyte count, and APACHE II and SOFA scores were compared. RESULTS: Significant changes in nitrogen balance, APACHE II and SOFA scores, and leukocyte count were found in the study group (p<0.001, p<0.0001, p<0.0001, p<0.05, respectively), whereas no significant differences were detected in the control group. Cultures were positive in nine patients in the immunonutrition group, and in 12 patients in the control group. Septic shock and mortality rates were 26% and 20% in the study patients, and 40% and 33% in the controls, respectively (p>0.05). CONCLUSION: Patients receiving immunonutrition exhibit better nutritional status and improved scores showing clinical severity and organ failure.