Comparison of three transfusion protocols prior to central venous catheterization in patients with cirrhosis: A randomized controlled trial.

BACKGROUND: Transfusion of blood components prior to invasive procedures in cirrhosis patients is high and associated with adverse events. OBJECTIVES: We compared three transfusion strategies prior to central venous catheterization in cirrhosis patients. PATIENTS/METHODS: Single center randomized trial that included critically ill cirrhosis patients with indication for central venous line in a tertiary private hospital in Brazil. INTERVENTIONS: Restrictive protocol, thromboelastometry-guided protocol, or usual care (based on coagulogram). The primary endpoint was the proportion of patients transfused with any blood component (ie, fresh frozen plasma, platelets, or cryoprecipitate). The secondary endpoints included incidence of bleeding and transfusion-related adverse events. RESULTS: A total of 57 patients (19 per group; 64.9% male; mean age, 53.4 ± 11.3 years) were enrolled. Prior to catheterization, 3/19 (15.8%) in the restrictive arm, 13/19 (68.4%) in the thromboelastometry-guided arm, and 14/19 (73.7%) in the coagulogram-guided arm received blood transfusion (odds ratio [OR], 0.07; 95% confidence interval [CI], 0.01-0.45; P = .002 for restrictive versus coagulogram-guided arm; OR, 0.09; 95% CI, 0.01-0.56; P = .006 for restrictive versus thromboelastometry-guided arm; and OR, 0.77; 95% CI, 0.14-4.15; P = .931 for thromboelastometry-guided versus coagulogram-guided arm). The restrictive protocol was cost saving. No difference in bleeding, length of stay, mortality, and transfusion-related adverse events was found. CONCLUSIONS: The use of a restrictive strategy is associated with a reduction in transfusion prior to central venous catheterization and costs in critically ill cirrhosis patients. No effect on bleeding was found among the groups.

Recent advances in mechanical ventilation in patients without acute respiratory distress syndrome.

While being an essential part of general anesthesia for surgery and at times even a life-saving intervention in critically ill patients, mechanical ventilation has a strong potential to cause harm. Certain ventilation strategies could prevent, at least to some extent, the injury caused by this intervention. One essential element of so-called 'lung-protective' ventilation is the use of lower tidal volumes. It is uncertain whether higher levels of positive end-expiratory pressures have lung-protective properties as well. There are indications that too high oxygen fractions of inspired air, or too high blood oxygen targets, are harmful. Circumstantial evidence further suggests that spontaneous modes of ventilation are to be preferred over controlled ventilation to prevent harm to respiratory muscle. Finally, the use of restrictive sedation strategies in critically ill patients indirectly prevents ventilation-induced injury, as daily spontaneous awakening and breathing trials and bolus instead of continuous sedation are associated with shorter duration of ventilation and shorten the exposure to the injurious effects of ventilation.

Reversion of gene expression alterations in hearts of mice with chronic chagasic cardiomyopathy after transplantation of bone marrow cells.

Chronic chagasic cardiomyopathy is a leading cause of heart failure in Latin American countries, being associated with intense inflammatory response and fibrosis. We have previously shown that bone marrow mononuclear cell (BMC) transplantation improves inflammation, fibrosis, and ventricular diameter in hearts of mice with chronic Chagas disease. Here we investigated the transcriptomic recovery induced by BMC therapy by comparing the heart transcriptomes of control, chagasic, and BMC transplanted mice. Out of the 9390 unique genes quantified in all samples, 1702 had their expression altered in chronic chagasic hearts compared to those of normal mice. Major categories of significantly upregulated genes were related to inflammation, fibrosis and immune responses, while genes involved in mitochondrion function were downregulated. When BMC-treated chagasic hearts were compared to infected mice, 96% of the alterations detected in infected hearts were restored to normal levels, although an additional 109 genes were altered by treatment. Transcriptomic recovery, a new measure that considers both resotrative and side effects of treatment, was remarkably high (84%). Immunofluorescence and morphometric analyses confirmed the effects of BMC therapy in the pattern of inflammatory-immune response and expression of adhesion molecules. In conclusion, by using large-scale gene profiling for unbiased assessment of therapeutic efficacy we demonstrate immunomodulatory effects of BMC therapy in chronic chagasic cardiomyopathy and identify potentially relevant factors involved in the pathogenesis of the disease that may provide new therapeutic targets.

Bone marrow cell therapy ameliorates and reverses chagasic cardiomyopathy in a mouse model.

Chronic chagasic cardiomyopathy, which is caused by the protozoan Trypanosoma cruzi, is a major cause of heart failure in Latin America. It is a disease for which effective treatment in its advanced clinical forms is lacking. We have previously shown that bone marrow mononuclear cell (BMC) transplantation is effective in reducing inflammation and fibrosis in the mouse model of Chagas disease. The present study used magnetic resonance imaging to assess changes in the cardiac morphology of infected mice after therapy with BMCs. Serial imaging of the BMC-treated mice revealed regression of the right ventricular dilatation typically observed in the chagasic mouse model.

Transplanted bone marrow cells repair heart tissue and reduce myocarditis in chronic chagasic mice.

A progressive destruction of the myocardium occurs in approximately 30% of Trypanosoma cruzi-infected individuals, causing chronic chagasic cardiomyopathy, a disease so far without effective treatment. Syngeneic bone marrow cell transplantation has been shown to cause repair and improvement of heart function in a number of studies in patients and animal models of ischemic cardiopathy. The effects of bone marrow transplant in a mouse model of chronic chagasic cardiomyopathy, in the presence of the disease causal agent, ie, the T. cruzi, are described herein. Bone marrow cells injected intravenously into chronic chagasic mice migrated to the heart and caused a significant reduction in the inflammatory infiltrates and in the interstitial fibrosis characteristics of chronic chagasic cardiomyopathy. The beneficial effects were observed up to 6 months after bone marrow cell transplantation. A massive apoptosis of myocardial inflammatory cells was observed after the therapy with bone marrow cells. Transplanted bone marrow cells obtained from chagasic mice and from normal mice had similar effects in terms of mediating chagasic heart repair. These results show that bone marrow cell transplantation is effective for treatment of chronic chagasic myocarditis and indicate that autologous bone marrow transplant may be used as an efficient therapy for patients with chronic chagasic cardiomyopathy.