Yoshimi Nakanishi

Cytokines and plasminogen activator inhibitor-1 in posttrauma disseminated intravascular coagulation: relationship to multiple organ dysfunction syndrome.

OBJECTIVESna) To investigate the relationships between tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), plasminogen activator inhibitor-1, and disseminated intravascular coagulation (DIC); b) to determine the influence of DIC on the mortality rate, adult respiratory distress syndrome (ARDS), and multiple organ dysfunction syndrome; and c) to find a useful prognostic index for outcome.nnnDESIGNnProspective, case-control study.nnnSETTINGnGeneral intensive care unit (tertiary care center) in a city hospital serving a population of 1.5 million people.nnnPATIENTSnFifty-eight trauma patients; 22 of the patients with DIC and 36 of the patients without DIC.nnnINTERVENTIONSnNone.nnnMEASUREMENTS AND MAIN RESULTSnTNF-alpha, IL-1 beta, plasminogen activator inhibitor-1 activity, and plasminogen activator inhibitor-1 antigen concentration were measured on the day of the injury, and on days 1, 3, and 5 after admission. The results of these measurements, demographic data, severity of illness score, mortality rate in the intensive care unit and frequencies of ARDS, multiple organ dysfunction syndrome, and sepsis were compared according to the occurrence of DIC. DIC patients were classified into subgroups of survivors and nonsurvivors, and the changes in plasminogen activator inhibitor-1 between subgroups were studied. The Acute Physiology and Chronic Health Evaluation II scores, the Injury Severity Scores, and the frequency of ARDS and multiple organ dysfunction syndrome were higher in the DIC patients. The mortality rate of the DIC patients was higher than the rate of the non-DIC patients (59.0% vs. 13.8%; p = .0009). TNF-alpha and IL-1 beta concentrations increased more in the DIC patients than in the non-DIC patients. Plasminogen activator inhibitor-1 activity and plasminogen activator inhibitor-1 antigen concentrations in the DIC patients, especially those values in the nonsurvivors, continued to be markedly high up to day 5 of admission. The most favorable prognostic value of plasminogen activator inhibitor-1 for the prediction of death in all of the trauma patients and the DIC patients was determined on days 3 and 5, respectively. No significant correlation was noted between the two cytokines and plasminogen activator inhibitor-1.nnnCONCLUSIONSnIn the patients with trauma, DIC is a predictor of ARDS, multiple organ dysfunction syndrome, and death. TNF-alpha and IL-1 beta might be one of the causes of DIC, while plasminogen activator inhibitor-1 may be one of the aggravating factors of ARDS and multiple organ dysfunction syndrome. Plasminogen activator inhibitor-1 is a good predictor of death for posttrauma DIC patients.

Participation of tissue factor and thrombin in posttraumatic systemic inflammatory syndrome

OBJECTIVEnTo determine the roles of tissue factor and thrombin on the systemic inflammatory response syndrome (SIRS) in posttrauma patients, as well as to investigate the relationship between SIRS and sepsis.nnnDESIGNnProspective, cohort study.nnnSETTINGnGeneral intensive care unit of a tertiary care emergency department.nnnPATIENTSnForty trauma patients were classified into subgroups, according to the duration of SIRS: non-SIRS patients (n = 9); patients with SIRS for < 2 days (n = 15); and patients with SIRS for > 3 days (n = 16).nnnINTERVENTIONSnNone.nnnMEASUREMENTS AND MAIN RESULTSnTissue factor antigen concentration, prothrombin fragment F1+2, thrombin antithrombin complex, fibrinopeptide A, and cross-linked fibrin degradation products (D-dimer) were measured on the day of admission, and on days 1 through 4 after admission. Simultaneously, the number of SIRS criteria that the patients met and the disseminated intravascular coagulation score were determined. The results of these measurements, frequency of acute respiratory distress syndrome (ARDS), multiple organ dysfunction syndrome, sepsis, and outcome were compared among the groups. The values of all five hemostatic molecular markers in the patients with SIRS for > 3 days were significantly more increased than those molecular marker values measured in the other groups on the day of admission. These values continued to be markedly high up to day 4 of admission. The occurrence rates of disseminated intravascular coagulation in these patient groups were significantly higher than those rates in the other two groups (p = .0001), and the disseminated intravascular coagulation scores did not improve during the study period. The occurrence rates of ARDS (p < .05) and multiple organ dysfunction syndrome (p < .01) were higher in patients with SIRS for > 3 days compared with those rates in the other groups, and the patients with SIRS for > 3 days had a poor outcome. No significant difference was noted in the frequency of sepsis among the groups.nnnCONCLUSIONSnSustained SIRS is the main determinant for ARDS, multiple organ dysfunction syndrome, and outcome in posttrauma patients. Disseminated intravascular coagulation associated with massive thrombin generation and its activation is involved in the pathogenesis of sustained SIRS. Sepsis has a small role in early posttrauma multiple organ dysfunction syndrome.

Cytokines, soluble thrombomodulin and disseminated intravascular coagulation in patients with systemic inflammatory response syndrome

To investigate the relationships between tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1 beta), soluble thrombomodulin (TM), and disseminated intravascular coagulation (DIC) in patients with systemic inflammatory response syndrome (SIRS), twenty-nine SIRS patients were classified into three groups; 4 patients without DIC, 8 DIC patients who recovered, and 17 DIC patients who did not recover. Serum TNF, IL-1 beta, and soluble TM were measured on the day of the diagnosis of SIRS, and also on the 1st, 3rd, 5th days. All of the DIC patients had multiple organ dysfunction syndrome (MODS) and the number of the dysfunctioning organs showed significant differences between the groups (p = .0017). All of the patients who did not recover from DIC died. The serum soluble TM level was higher in the patients without DIC recovery than in either the DIC recovery patients or the non DIC patients throughout the study period. In DIC patients who did not recover, there were significant correlations between soluble TM and TNF (r2 = 0.205, p = .0003) or IL-1 beta (r2 = 0.157, p = .0036). In conclusion, the DIC being associated with endothelial injury is an important pathogenetic factor for MODS and is a main determinant of the outcome of SIRS patients. TNF and IL-1 beta might be involved in the cause of this endothelial injury. The soluble TM is a good predictor of organ dysfunction and also of a poor prognosis.

Soluble thrombomodulin increases in patients with disseminated intravascular coagulation and in those with multiple organ dysfunction syndrome after trauma : role of neutrophil elastase

OBJECTIVEnOur goal was to investigate the role of soluble thrombomodulin (TM) and neutrophil elastase in patients with trauma.nnnDESIGNnThis study is a prospective case-control study.nnnMATERIALS AND METHODSnForty-seven trauma victims, 14 with disseminated intravascular coagulation (DIC), 5 with multiple organ dysfunction syndrome (MODS), and 28 control patients without DIC or MODS were the participants. Soluble TM and neutrophil elastase (elastase-alpha1-proteinase inhibitor complex) were measured on the day of the injury, and on the first, third, and fifth days after admission. The results of these measurements and demographic data were compared among the groups, and correlations between the soluble TM and the neutrophil elastase were examined. The DIC patients were classified into subgroups of survivors (n = 5) and nonsurvivors (n = 9), and the changes of the soluble TM between the subgroups were then studied.nnnMEASUREMENTS AND MAIN RESULTSnA high incidence of DIC patients encountered MODS complications (12 of 14, 86%). The DIC patients had higher Injury Severity Scores (ISSs) than the other patients. The levels of soluble TM and neutrophil elastase significantly increased on the day of admission in the patients with DIC and also in those with MODS (p < 0.05 vs. control patients) and continued to show markedly high values until the fifth day of admission in the patients with DIC. In the DIC patients, the levels of soluble TM were higher in the nonsurvivors than in the survivors (p < 0.05 on the third and the fifth days of admission). In all patients, there was weak but statistically significant correlation between peak levels of soluble TM and ISS (r2 = 0.125, p < 0.025). Comparison of the levels of soluble TM and neutrophil elastase in the patients with DIC or MODS demonstrated an excellent correlation (r2 = 0.718 and r2 = 0.714, respectively).nnnCONCLUSIONSnSoluble TM as a novel endothelial cell injury marker increases in patients with DIC and also in those with MODS after trauma. Neutrophil elastase may be involved in the pathogenesis of the injury. Soluble TM is a marker of the severity of injury and is a good predictor of MODS.

Increased neutrophil elastase, persistent intravascular coagulation, and decreased fibrinolytic activity in patients with posttraumatic acute respiratory distress syndrome

BACKGROUNDnTo investigate the role of plasma neutrophil elastase (elastase-alpha1-proteinase inhibitor complex), plasminogen activator inhibitor-1 (PAI-1), and disseminated intravascular coagulation (DIC) in patients with posttraumatic acute respiratory distress syndrome (ARDS) and to explore the time course of the changes of these factors after trauma, we performed a prospective case-control study.nnnMETHODSnThe study subjects consisted of 41 trauma patients, 5 with ARDS, 7 at risk for but not developing the syndrome, and 29 control patients without or with no risk for ARDS. Plasma neutrophil elastase, PAI-1 activity, and PAI-1 antigen concentration were measured on the day of the injury and on days 1, 3, and 5 after admission. DIC was measured on the basis of the DIC score. The results of these measurements and demographic data were compared among the three groups.nnnRESULTSnNeutrophil elastase, PAI-1 activity, and PAI-1 antigen concentration for the ARDS patients continued to be markedly high until the fifth day of admission, and the values on the fifth day were significantly higher than those of the other two groups. All patients with ARDS developed DIC. A decrease in the DIC score was found for the control patients and also for the patients at risk for ARDS; however, for the patients with ARDS, the DIC score did not improve during the study period (p = 0.5809).nnnCONCLUSIONnWe provide precise information on the time course of neutrophil elastase, PAI-1, and DIC in trauma patients with ARDS and those at risk of developing this syndrome. Neutrophil activation and persistent intravascular coagulation as well as impaired fibrinolysis may play a role in the pathogenesis of posttraumatic ARDS.

Pharmacokinetics and clearance of ganciclovir during continuous hemodiafiltration.

OBJECTIVEnTo evaluate the ganciclovir pharmacokinetics and clearance during continuous venovenous hemodiafiltration.nnnDESIGNnCase report.nnnSETTINGnGeneral intensive care unit of a tertiary care emergency department.nnnPATIENTSnA 63-yr-old female who has a history of active behçets disease that has been controlled with oral prednisolone, and who has chronic renal failure.nnnINTERVENTIONSnNone.nnnMEASUREMENTS AND MAIN RESULTSnA 5-mg/kg dosage of ganciclovir was administered intravenously over a 60-min period under continuous venovenous hemodiafiltration. Samples from the arterial and venous blood catheters and from the ultradiafiltrate were collected over the next 12 hrs to calculate pharmacokinetic parameters and clearance of hemodiafiltration. The pharmacokinetic parameters were as follows: half-life of elimination phase 12.6 hrs; total clearance 0.55 mL/min/kg; and volume distribution of steady state 27.07 L. The clearance of hemodiafiltration was 0.63 mL/min/kg.nnnCONCLUSIONnContinuous venovenous hemodiafiltration is effective in removing ganciclovir from the blood.