Evren Senturk

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)

The frequency, risk factors, and complications of gastrointestinal dysfunction during enteral nutrition in critically ill patients

Background Gastrointestinal (GI) motility disorders in intensive care patients remain relatively unexplored. Nowadays, the frequency, risk factors and complications of GI dysfunction during enteral nutrition (EN) become more questionable. Aim To evaluate the frequency, risk factors and complications of GI dysfunction during EN in the first 2 weeks of the intensive care unit (ICU) stay and to identify precautions to prevent the development of GI dysfunction and avoid complications. Methods In this prospective observational study, we deliberately targeted at-risk patients. A total of 137 patients who received nasogastric tube feeding in an ICU of a tertiary hospital were enrolled. Results The incidence of GI dysfunction that was found to be 63% which was associated mainly between MDR bacteria positivity and negative fluid balance. Diarrhea was observed in 36 patients (26%) and on 147 patient-days (incidence rate, 5.5 per 100 patient-days). The median day of diarrhea onset was 6 days after the initiation of EN. Forty patients (29%) presented with constipation (85% during the first week). Fifty patients (36%) exhibited upper digestive intolerance on 212 patient-days (incidence rate, 7.9 per 100 patient-days), after a median EN duration of 6 days (range, 2–14 days). Logistic regression analysis revealed MDR bacteria growth in the culture (OR, 1.75; 95% CI, 1.15–2.67; P=0.008) and negative fluid balance (OR, 0.57; 95% CI, 0.34–0.94; P=0.03) as the risk factors for GI dysfunction. We also showed that GI dysfunction was associated with high SOFA score, hypoalbuminemia, catecholamine use, and prolonged length of stay (LOS). GI dysfunction, on the other hand, can cause some complications including inadequate nutrition, and newly developed decubitus ulcers. Conclusion GI dysfunction should be considered a clinical predictor of inadequate nutrition and prolonged LOS. In addition, the most dramatic risk for GI dysfunction was observed in patients with MDR bacteria growth in the culture and patients in negative fluid balance. Intensivists provide appropriate nutrition for patients, as well as prompt intervention and the development of treatment strategies in the event of GI dysfunction.

Effects of different recruitment maneuvers on bacterial translocation and ventilator- induced lung injury.

BACKGROUND Investigated in the present study were the effects of various recruitment maneuvers (RMs) using the same inflation pressure-time product on bacterial translocation from lung to blood, and ventilator-induced lung injury (VILI). METHODS Tracheotomy was performed on anesthetized rats, and ventilation was initiated using pressure-controlled mode. Subsequently, Pseudomonas aeruginosa was inoculated through the tracheotomy tube and ventilated for 30 minutes before rats were randomly separated into 4 groups. Group 1 underwent sustained inflation (SI), Group 2 underwent low-pressure SI, Group 3 underwent modified sigh, and Group 4 was a control group. Blood cultures were taken at baseline, 15 minutes after randomization (after each RM for the first hour), and finally at 75 minutes after the last RM. The rats were euthanized and the lungs were extirpated. The left lung was taken for measurement of wet:dry weight ratio, and the right lung was used for pathologic evaluation. RESULTS Positive blood cultures were found to be higher in Group 3 at early study periods. Total pathological scores were also higher in Group 3. CONCLUSION Higher severity of ventilator-induced lung injury occurred in the modified sigh group, evidenced by bacterial translocation and results of histopathological evaluation.

Effect of recruitment maneuver on hypoxemia during apnea test: after or before?

Apnea test is an obligatory test confirming brain death, but can also challenge the oxygenation of potential donor organs. A recruitment maneuver after the apnea test has been reported to prevent hypoxemia. We have previously reported that a recruitment maneuver before the apnea test followed by apneic oxygenation can have also beneficial effects on oxygenation; and also improve the survival time. In our study, the increase in PaCO2 has not been affected after the recruitment maneuver. A recruitment maneuver before and/or after the apnea test can be beneficial; and possible effects on CO2 elimination should also be kept in mind.