Saori Ohtsubo

Serum albumin levels anticipate antithrombin III activities before and after antithrombin III agent in critical patients with disseminated intravascular coagulation.

Elevated thrombin-antithrombin complex (TAT) or decreased serum albumin levels suggest heightened vascular permeability in disseminated intravascular coagulation (DIC). In such a situation, plasma antithrombin III (AT-III) may decrease because of the leakage. We thus examined whether AT-III activity before and after administration of an AT-III agent changed depending on plasma TAT and/or serum albumin levels in 20 consecutive patients with DIC. We also analyzed the pharmacokinetics for AT-III using a two-compartment model. Serum albumin levels before AT-III administration correlated with preadministered and postadministered AT-III activity, but TAT levels did not. Regardless of TAT levels, AT-III trough activity on the third day increased significantly. In patients with albumin levels of 2.5 g/dL or less, AT-III trough levels on the third day were significantly lower than those with higher levels of albumin. The half-life of the distribution phase for AT-III agent in the patients was shortened to less than one third the value reported in congenital AT-III deficiency, suggesting increased vascular permeability in the acute state patients here. The distribution volume of the agent increased remarkably compared with the previous control. We report here for the first time that in critical patients with DIC, plasma AT-III levels before and after AT-III administration could be predicted by preadministered serum albumin levels, but not by TAT. These findings could be explained by the pharmacokinetic profile, increased vascular permeability and distribution volume, observed in critical patients.

Effects of Dexamethasone on Pulmonary Oxygenation Impairments inTherapeutic Hypothermia for Patients with Traumatic Brain Injury

Objectives: We studied retrospectively to examine differences in the occurrence rate of pneumonia and the time-course changes in pulmonary oxygenation between hypothermic and normothermic therapies with or without dexamethasone (D) administration in patients with traumatic brain injury (TBI). Design: A retrospective observational study. Setting: Two university hospitals. Subjects and Methods: In consecutive TBI patients (GCS ≤ 8) treated with hypothermic (N=23, 32-33°C) or normothermic (N=16, 36-37.5°C) therapy, the occurrence rate of pneumonia, PaO2/FIO2 (P/F) ratios and C-reactive protein (CRP) levels were examined. The comparisons were made among hypothermic and normothermic groups with or without D administration. In several patients in both groups, neutrophil functions were examined. Data were analyzed with ANOVA followed by Sheffe’s F-test, Mann-Whitney U-test, Kruskal-Wallis tests or chi-squared test (p<0.05) as appropriate. Results: The occurrence rate of pneumonia in a hypothermic group with D administration was significantly lower than in a hypothermic group without D. In the hypothermic group without D treatment, CRP elevation during the rewarming phase occurred, which was followed by more severe P/F ratio deteriorations as compared to the hypothermic group given D. Neutrophil phagocytic functions in hypothermic patients without D were activated around 35°C, which were followed by marked decreases in pulmonary oxygen. In contrast, phagocytic function in a hypothermic patient receiving D was depressed, but without P/F ratios below 280. Conclusion: This study poses hypotheses that neutrophils play a role in the pulmonary oxygenation impairment in hypothermic therapy for TBI patients, and that dexamethasone improves the pulmonary complications in therapeutic hypothermia.