RESUMEN
Study objective: Antithrombin (AT) activity is reduced during cardiopulmonary bypass (CPB) surgery. Guidelines has demonstrated that perioperative AT supplementation contributed to blood conservation and prevent perioperative thrombotic complications and target organ injury owing to its role in reducing thrombin generation. But these recommends is lack of support of meta-analysis in the guidelines. This meta-analysis aims to include all the relevant randomized controlled trails (RCT) on patients who experienced cardiac surgeries with CPB and investigate the effect of perioperative AT on blood conservation and complications after cardiac surgery. Methods: Standard published RCTs were searched from bibliographic databases to identify all evidence reporting perioperative AT supplementation for patients undergoing cardiovascular surgeries. The primary outcome was postoperative blood loss, the secondary outcomes were blood component transfusion (red blood cell (RBC), fresh frozen plasma (FFP), platelet and autologous blood), postoperative morbidity and in hospital mortality. The relative risk (RR) for dichotomous outcomes and the standardized mean difference (SMD) for continuous outcomes were estimated using a random-effects model. Trial sequential analysis (TSA) was performed using TSA software 0.9.5.10. Results: 13 RCTs with 996 participants undergoing different cardiovascular surgeries were included. Meta-analysis showed AT did not decrease postoperative blood loss (SMD -0.01, 95%CI -0.2 to 0.19). Subgroup analysis showed the effect of AT on postoperative blood loss was not associated with age, RCT type, surgery type, injection time of AT and AT deficiency. TSA further suggested that no additional studies were required for the stable result. Perioperative AT also did not reduce RBC ((SMD 0.10, 95%CI -0.66 to 0.85), (RR 0.99, 95%CI 0.83 to 1.19)), FFP ((SMD 0.11, 95%CI -0.19 to 0.41), (RR 1.30, 95%CI 0.90 to 1.87)), platelet (RR 1.10, 95%CI 0.83 to 1.46) and autologous blood (SMD 0.46, 95%CI -0.12 to 1.8504) transfusions. Perioperative AT significantly increased in hospital mortality (RR 2.53, 95%CI 1.02 to 6.28) and acute kidney injury (AKI) (RR 3.72, 95%CI 1.73 to 8.04) incidence. There was no significant difference in postoperative reexploration, thromboembolism, ECMO/IABP support, and stroke incidence between AT and non-AT group. Conclusions: With the improvement of AT level and heparin sensitivity, perioperative AT has no significant effect on blood conservation. And it is noteworthy that the treatment increased in hospital mortality and the incidence of AKI after cardiac surgery.
RESUMEN
OBJECTIVE: To investigate the effect of mild hypothermia preconditioning against ischemia/reperfusion (I/R) injury of cultured primary cortical rats neurons, and to compare the protective effect of mild hypothermia only and with its combination with drugs. METHODS: Cortical neurons of neonatal Sprague-Dawley (SD) rat within 24 hours after birth were harvested and cultured in vitro. On the 3rd day, the cells were cultured in a medium containing 2.5 mg/L cytosine arabinoside to inhibit the growth of glial cells and fibroblast. Having cultured for 6 days they were randomly divided into blank control group, glutamate damaged group (cultured with 200 µmol/L glutamate for 0.5 hour after washing), mild hypothermia preconditioning group (cultured under 33.5 centigrade for 24 hours before injury induced by glutamate), mild hypothermia combining with edaravone preconditioning group, and the hypothermia combining with propofol preconditioning group (medium containing 100 µmol/L edaravone and 3 mg/L propofol). They were cultured under 33.5 centigrade for 24 hours before injury induced by glutamate. After 24 hours of culturing in various medium, apoptosis ratio was observed by flow cytometry. Cell surviving rate was determined with methyl thiazolyl triazolium (MTT), c-fos protein expression was assayed, and morphologic change of cells with hematoxylin-eosin (HE) staining under the microscope, and ultrastructure changes were observed after uranyl acetate and lead citrate staining under transmission electron microscope. RESULTS: The apoptosis ratio and c-fos protein in glutamate damaged group were significantly higher than those in blank control group [apoptosis ratio: (9.85±0.76)% vs. (0.94±0.20)%, c-fos: 6.96±0.75 ng/L vs. 1.65±0.59 ng/L, both P<0.01], the cell surviving rate was significantly lower than that in blank control group [(0.20±0.02)% vs. (0.97±0.03)%, P<0.01]. Mild hypothermia preconditioning reversed surviving rate, apoptosis ratio and c-fos protein, and the effect of hypothermia combining with propofol preconditioning was obviously better [cell surviving rate: (0.80±0.04)% vs. (0.20±0.02)%, apoptosis ratio: (2.26±0.54)% vs. (9.85±0.76)%, c-fos: 2.98±0.46 ng/L vs. 6.96±0.75 ng/L, all P<0.01]. The morphology of cortical neurons in blank control group was normal. Most of the cells in glutamate damaged group showed bluish black cytoplasm with pyknic nuclei, with crumpled axons and of them were fractured, and cell number was obviously decreased. In each pre-conditional group, decrease in cell number was unconspicuous, and only a few cells showed apoptosis. Under transmission electron microscope, it was found that cell membrane, mitochondria and rough endoplasmic reticulum were intact in blank control group, but with reduction in organelles, severely swollen mitochondria, even with formation of vacuole or pyknosis, serious dilation of rough endoplasmic reticulum, with loss of cristae with loss of vacuoles or pyknosis, and marked dilatation of internal reticular endoplasm, and loss of cristae with vacuolation and chromatin were observed under electron microscope in glutamate damaged group. Compared with the glutamate damaged group, these pathologic changes were markedly alleviated in protected groups. CONCLUSIONS: Mild hypothermia preconditioning can inhibit glutamate-induced injury to cortical neurons. The protective effect of mild hypothermia combined with propofol is better.
