Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Randomized Controlled Trial
Thrombomodulin alfa in the treatment of infectious patients complicated by disseminated intravascular coagulation: subanalysis from the phase 3 trial.
To investigate treatment effects of thrombomodulin alfa (TM-α) in patients with disseminated intravascular coagulation (DIC) having infection as the underlying disease, retrospective subanalysis of a double-blind, randomized controlled phase 3 trial was conducted. In the phase 3 trial, 227 DIC patients (full-analysis set) having infection and/or hematologic malignancy as the underlying disease received either TM-α (0.06 mg·kg for 30 min once daily) or heparin (8 U·kg·h for 24 h) for 6 days using the double-dummy method. Among these patients, 147 patients with noninfectious comorbidity leading to severe thrombocytopenia (e.g., hematologic malignancy, or aplastic anemia) were excluded from the present analysis, and 80 patients with infectious disease and DIC were extracted and subjected to the present retrospective subanalysis. ⋯ In the TM-α and heparin groups, DIC resolution rates were 67.5% (27/40) and 55.6% (20/36), and 28-day mortality rates were 21.4% (9/42) and 31.6% (12/38), respectively. Mortality rates of patients who recovered from DIC were 3.7% (1/27) in the TM-α group and 15% (3/20) in the heparin group. These results suggest TM-α may be valuable in the treatment of DIC associated with infection.
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We studied whether low hemoglobin concentrations during normovolemia change the myocardial electrical current (electrocardiogram) in a pig model. Normovolemic anemia was achieved by stepwise replacing blood with colloids (hydroxyethyl starch 6%). We measured the length of the PQ-, QT-, QTc, and the ST interval as well as the amplitude of the Q wave and T wave at hemoglobin concentrations of 9.5, 8.0, 5.5, 3.8, and 3.3 g·dL. ⋯ Results were verified performing a time-frequency analysis on single heartbeats. During severe anemia and normovolemia, electrocardiographic changes can be detected. Further investigations are warranted to elucidate whether these changes indicate myocardial hypoxia.
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Disseminated intravascular coagulation contributes to mortality of sepsis. The study was performed to investigate thromboelastometry as a potential predictor of 30-day survival in severe sepsis and to compare thromboelastometry to Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) scores. Ninety-eight patients with severe sepsis were included in the cohort study. ⋯ Thromboelastometry values were normal if CFT was less than 185 s, MCF was greater than 55 mm, and α was greater than 57.5 degrees. Thirty-day survival was 85.7% when all thromboelastometry variables were normal, but 58.7% when at least one variable was pathological (P = 0.005). Multivariate analysis revealed that the absence or presence of at least one pathological thromboelastometry variable allows for better prediction of 30-day survival in severe sepsis than the SAPS II and SOFA scores (P = 0.01; odds ratio, 4.1), respectively, emphasizing the importance of the coagulation system in sepsis.
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Femoral venous access is frequently used in critically ill patients. Because raised intra-abdominal pressure (IAP) is also frequently found in this group of patients, we examined the impact of IAP and positive end-expiratory pressure (PEEP) on femoral venous pressure (FVP) and femoral venous oxygen saturation (Sfvo2) in an animal model. Thirteen adult pigs received standardized anesthesia and ventilation. ⋯ However, a raised FVP should prompt the measurement of the bladder pressure. Femoral venous oxygen saturation did correlate neither with Svo2 nor with abdominal perfusion pressure. Therefore, Sfvo2 is of no clinical use in the setting of raised IAP.
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Experimental data have shown that mesenteric lymph from rats subjected to trauma-hemorrhagic shock (THS) but not trauma-sham shock induces neutrophil activation, cytotoxicity, decreased red blood cell (RBC) deformability, and bone marrow colony growth suppression. These data have led to the hypothesis that gut factors produced from THS enter the systemic circulation via the mesenteric lymphatics and contribute to the progression of multiple organ failure after THS. Ongoing studies designed to identify bioactive lymph agents implicated factors associated with the heparin use in the THS procedure. ⋯ Finally, incubation of HUVECs with purified lipoprotein lipase added to naive lymph-induced toxicity in vitro. These data show that heparin, not THS, is responsible for the reported lymph-mediated HUVEC toxicity through its release of lipases into the lymph. These findings can provide alternative explanations for several of the THS effects reported in the literature using heparin models, thus necessitating a review of previous work in this field.