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

OBJECTIVES: a) 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. DESIGN: Prospective, case-control study. SETTING: General intensive care unit (tertiary care center) in a city hospital serving a population of 1.5 million people. PATIENTS: Fifty-eight trauma patients; 22 of the patients with DIC and 36 of the patients without DIC. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: TNF-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. CONCLUSIONS: In 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.

Fibrinolytic shutdown after cardiopulmonary bypass surgery is caused by circulating cytokines during operation, accompanied by endothelial injury.

It has been hypothesized that increased cytokines during cardiopulmonary bypass surgery cause postoperative fibrinolytic shutdown. To investigate the role of cytokines and to elucidate its mechanism, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), plasminogen activator inhibitor-1 antigen (PAI-1 Ag), PAI-1 activity, and thrombomodulin in 16 patients undergoing elective cardiopulmonary bypass surgery were analyzed after induction of anesthesia, before and after cardiopulmonary bypass, and at the end of the operation. during surgery, TNF-α and LI-1ß were detected in 44% and 63% of the cases, respectively. PAI-1 Ag (P<0.01), PAI-1 activity (P<0.001) and thrombomodulin (P<0.01) were significantly increased at the end of the operation. The patients were divided into two groups and examined: Group 1 with either cytokine detected (n=12); and group 2 without detection of cytokines (n=4). At the end of the operation, both PAI-1 Ag (P<0.05) and PAI-1 activity (P<0.01) were significantly increased in group 1 compared with group 2. In group 1, there was a significant positive correlation between thrombomodulin and PAI-1 Ag (r (2)=0.117,P<0.05) and PAI-1 activity (r (2)=0.124,P<0.05). In conclusion, TFN-α and IL-1ß were released into the systemic circulation during cardiopulmonary bypass surgery, and this release may have been caused by vascular endothelial injury. These cytokines increased PAI-1 activity.

[Increased fibrinolytic activity during cardiopulmonary bypass is caused by activated protein C system].

To examine the hypothesis that activated protein C system during cardiopulmonary bypass surgery may increase fibrinolytic activity during cardiopulmonary bypass, protein C activity, protein C antigen and thrombomodulin of sixteen patients undergoing elective cardiopulmonary bypass surgery were investigated after induction of anesthesia, before and after cardiopulmonary bypass, and at the end of operation. Protein C activity decreased and thrombomodulin increased significantly after the cardiopulmonary bypass. There were no significant correlations of thrombomodulin with protein C activity and protein C antigen. In conclusion, we have demonstrated that protein C system is activated and circulating thrombomodulin appears in the systemic circulation during cardiopulmonary bypass surgery and this enhanced activation of protein C system is possibly related to the reported increase of fibrinolytic activity during cardiopulmonary bypass.

Blunt liver trauma: a new concept for classification of liver trauma based on vessel injury.

We reviewed a consecutive 143 cases of blunt liver trauma, 43 children and 100 adults, to clarify the pathosis of liver trauma and to reasonably select treatment, non-operative or operative management. The primary determinant in the prognosis of liver trauma was clearly hemorrhage due to vessel injuries and its main treatment method was hemostasis. We developed a new concept for the classification of blunt liver trauma based on vessel injuries: I = subcapsular Glissonian vessel injuries, II = transcapsular Glissonian vessel injuries and III = in-/out-flow vessel injuries and 3 basic types were divided into 2 subtypes, respectively. Distribution of liver trauma according to the present classification was as follows: type I = 23% in child cases and 22% in adult cases, type II = 65% and 64% and type III = 12% and 14%, respectively. The main management was non-operative for type I, minor or major surgery for type II, and extended surgery for type III. The analysis of dead cases showed the following: I = 0% in child cases and 6% in adult, II = 60% and 55%; III = 40% and 39%, respectively. The first direct cause was hemorrhage: 60% in child cases and 49% in adult. The present classification was applicable for both child and adult patients, and presented a selection of management for liver trauma, suggesting the prognosis.

The effects of massive transfusion and haptoglobin therapy on hemolysis in trauma patients.

A retrospective study was conducted on 53 patients who suffered severe trauma to determine the severity of intravascular hemolysis, the variations of renal function after trauma, and the effects of transfusion and haptoglobin therapy on these factors. Serum total haptoglobin, total hemoglobin, and urine free hemoglobin were measured 0, 1, 3, and 5 days after the trauma and renal tubular function was evaluated by the urinary N-acetyl-beta-D-glucosaminidase (NAG) index. Patients were divided into two groups depending on whether or not haptoglobin was given: group A (n = 34) did not receive haptoglobin, and group B (n = 19) was administered 4,421 +/- 245 U haptoglobin based on clinical indications. The total transfusion volumes were 3,477 +/- 594 ml and 10,146 +/- 1,794 ml, in groups A and B, respectively (P < 0.01). In group A, total haptoglobin was remarkably decreased to 69.4 +/- 11.6 mg/dl on day 0, but recovered to within the normal range on day 3, while the total hemoglobin was increased and the urine hemoglobin was positive in 61.8% of the patients. In group B, decreases in total haptoglobin and increases in total hemoglobin were more remarkable, and 84.2% had a positive urine hemoglobin. On day 5, groups A and B had NAG indices of 18.8 +/- 3.3 and 133.6 +/- 33.8 U/L/creatinine respectively (P < 0.01). These findings led us to conclude that trauma caused hemolysis and that the administration of 4,000 U haptoglobin did not improve either the severity of hemolysis or the deteriorated renal tubular function caused by massive transfusion.

A case of abdominal cystic lymphangioma: cobweb appearance on ultrasonography.

A case of abdominal cystic lymphangioma is described. Our sonographic examination showed a large multilocular cyst with a cluster of honeycomb cysts revealing a cobweb appearance, which correlated with the pathologic specimen, and revealed characteristics of the disease. Sonographic appearance may be helpful in differentiating abdominal cystic lymphangioma from other multilocular cystic tumors.

Changes in coagulation and fibrinolytic activity associated with tracheal intubation.

This study was carried out to clarify the effect of tracheal intubation on the coagulation and fibrinolytic system. It was performed on 20 patients (ASA class 1-2) undergoing elective surgery. Before and after tracheal intubation, hemodynamics, ACTH, cortisol, catecholamines, and several coagulation and fibrinolytic factors were measured. Tracheal intubation was accompanied by significant increases in the blood pressure, heart rate, and norepinephrine level. No changes were observed in fibrinopetide A, fibrinopeptide B(Beta15-42), tissue plasminogen activator antigen, plasminogen, fibrinogen, and Alpha(2) plasmin inhibitor. Patients exposed to long intubation time (>20 seconds) were found to have a significantly higher level of fibrinopeptide A than patients with short tracheal intubation time (

[Increased fibrinolytic activity during surgery with cardiopulmonary bypass].

We studied blood coagulation and fibrinolysis in 19 patients during surgery with cardiopulmonary bypass (CPB). CPB was performed with a rotating pump and a membrane oxygenator. Heparinization was achieved with heparin 3 mg.kg-1 and the ACT value was kept above 400 seconds throughout the CPB. Heparin was neutralized by protamine at a ratio of 1:1-1.5 of the total amount of heparin. Blood was collected four times from an indwelling arterial line. We obtained the first sample immediately after induction of anesthesia, the second sample before heparinization, the third sample before protamine administration, and the fourth sample at the end of the operation. FPA, FPB beta 15-42, alpha 2PI-Pl-C, D-dimer, and the t-PA activity were measured. A statistically significant elevation of FPA was observed during the operation. FPB beta 15-42, alpha 2PI-Pl-C, and the D-dimer rose significantly immediately after the beginning of the CPB and these elevations continued until the end of the operation. The t-PA activity was elevated significantly only during the CPB. In conclusion, the t-PA is released from the endothelial cells during CPB by some undetermined mechanism (primary fibrinolysis). Then, plasmin is generated by the t-PA and this dissolves the fibrin clots formed by thrombin before the beginning of the CPB (secondary fibrinolysis). Enhanced fibrinolytic activity before and after the CPB is physiological secondary fibrinolysis.

[Wound healing, blood coagulation and fibrinolysis during operations involving gastric cancer surgery].

Serial changes of FPA, FPB beta 15-42, FN, XIIIa, and alpha 2PI were investigated for the study on wound healing, blood coagulation, and fibrinolysis during gastric cancer surgery. For a control, we compared the preoperative values with the postoperative ones. These results also were compared with the values in healthy volunteers and in patients with cholelithiasis or myoma uteri. Our findings were as follows; 1) Compared with the control values, a statistically significant elevation of FPA, FPB beta 15-42 and FPA/FPB beta 15-42 ratios in patients with gastric cancer was noticed after operation. 2) Compared with the control values, a statistically marked decrease of FN, XIIIa and alpha 2PI in patients with gastric cancer was observed after operation. 3) The preoperative FPA and FPB beta 15-42 levels of gastric cancer patients were appreciably greater than those of normal healthy volunteers. Compared with patients with cholelithiasis or myoma uteri, however, the only preoperative FPA of gastric cancer patients showed significantly high levels. 4) FN and alpha 2PI revealed a notable positive correlation. These results suggest (1) increase of coagulation activity (thrombin formation) in gastric cancer patients; (2) increase of intravascular coagulation and fibrinolytic activity (thrombin and plasmin formation) during gastric cancer surgery; and, (3) depression of FN, XIIIa and alpha 2PI during surgery was due to sequestration at the site of tissue injury.

[The influence and outcome of acute infantile intracranial hematoma with hypoxemia].

Unusually broad areas of cerebral infarction were demonstrated by CT scan in three head injured infants with acute intracranial hematoma. They revealed very characteristic CT findings including contralateral hemispheric ischemic zone. Case 1 is a 5-month-old boy who had hit his head 4 days before. On admission he was semicomatose and his respiration had suffered from generalized seizures with arterial PO2 value of 43 mmHg. CT scan revealed right subdural hematoma, and bihemispheric ischemic low density was also demonstrable. Hematoma clot weighing 10 grams was removed through emergency craniotomy, followed by external decompression. There was a marked atrophic change in the right cerebral hemisphere and contralateral frontal base during the following few months, but the basal ganglionic region, brainstem and cerebellum were hardly affected. The patient developed comparatively well mentally for the next one and a half years. Case 2 was a 2-year-old boy who had a previous history of moderate head trauma 8 hours before admission. After a lucid interval, sudden epileptic attacks hospitalized him in a condition of cardiopulmonary arrest. CT scan revealed severe epidural hematoma on the patient's right cerebrum. Emergency craniotomy was performed and hematoma 95 g in weight was removed followed by decompression. Postoperative CT showed broad ipsilateral ischemic edema including the contralateral cerebral hemisphere and brainstem. One and a half years later, the patient shows decorticated posture with ataxic respiration and negative light reflexes. Case 3 was an 8-month-old boy who had fallen down and hit his head on the floor. Status epilepticus had attacked him, causing him to be admitted in a dyspneic state.(ABSTRACT TRUNCATED AT 250 WORDS)

[Non-clostridial gas-producing brain abscess in a brain death patient--report of a case].

A 46 year old female was admitted to our emergency room because of cardiopulmonary arrest by hanging. After ten minutes cardiopulmonary resuscitation, she was resuscitated but her consciousness did'nt recover. CT-scans on the day of admission showed no abnormalities but on the second hospital day it showed symmetrical low density areas within the basal ganglia, the thalamus, the hippocampus, and the occipital lobe. There were marked enhanced effect in cerebral sulci due to cytotoxic edema of hypoxic encephalopathy. She was comatose for a week, her pupils were dilated, light reflex and other brain stem reflex were absent. CT-scans on the sixth hospital day showed marked brain swelling with disappearance of the ventricular systems (so called brain tamponade). Brain death was confirmed on the basis of Japanese Criteria on the seventh and tenth day of admission. She had been suffering from pneumonia and urinary tract infection with an elevation of temperature since the fourth hospital day. We detected Enterobacter Cloacae (E. Cloacae), Klebsiella Oxytoca from the cultures of sputum and urine. On the tenth hospital day her temperature was running up to 39.4 degrees C and blood count revealed a peripheral blood leucocytosis of 40,300/mm3 with a shift to the left. E. Cloacae was also detected from the cultures of blood. Skull roentgenogram showed multiple gas collections in the ventricular systems. CT-scans on the fourteenth hospital day showed multiple gas-containing brain abscess. The etiology of this infection was considered due to septicemia of E. Cloacae. She died from acute renal failure on the fifteenth hospital day. Consent for autopsy was not accepted.(ABSTRACT TRUNCATED AT 250 WORDS)

Can blood gas analysis indicate when mechanical ventilation should start in patients with acute myocardial infarction?

Arterial blood gas analysis of 69 patients with acute myocardial infarction were evaluated to provide a basis for respiratory care. Patients were divided into two groups: group A which received oxygen therapy only (n = 38) and group B which received oxygen therapy with mechanical ventilation (n = 31). The patients in group B were further divided into surviving cases (n = 14) and fatal cases (n = 17). On admission patients assigned to group B had lower PaO2 values than those placed in group A. In group B, there was no difference in the P/F value before mechanical ventilation of the surviving and the fatal cases, but the survivors demonstrated an improvement of the P/F value and an increase in cardiac index after mechanical ventilation. It may be reasonable to assume that a P/F value of less than 250 serves as an indicator for the initiation of mechanical ventilation. An increase in the P/F value after mechanical ventilation seems to be a valuable index to estimate prognosis in respiratory failure.