Recombinant human soluble thrombomodulin improves mortality in patients with sepsis especially for severe coagulopathy: a retrospective study

Background

Disseminated intravascular coagulation (DIC) is associated with high mortality in patients with sepsis. Several studies reporting that recombinant human soluble thrombomodulin (rhTM) reduced mortality in sepsis patients. This retrospective cohort study aimed to evaluate the efficacy of rhTM for patients with mild coagulopathy compared with those with severe coagulopathy.

Methods

We evaluated about 90-day mortality and SOFA score. SOFA score was also evaluated for the following components: respiratory, cardiovascular, hepatic, renal and coagulation.

Results

All 69 patients were diagnosed with sepsis, fulfilled Japanese Association for Acute Medicine criteria for DIC, and were treated with rhTM. Patients were assigned to either the mild coagulopathy group (did not fulfill the International Society on Thrombosis and Haemostasis overt DIC criteria) or the severe coagulopathy group (fulfilled overt DIC criteria). The 90-day mortality was significant lower in severe coagulopathy group than mild coagulopathy group (P?=?0.029). Although the SOFA scores did not decrease in the mild coagulopathy group, SOFA scores decreased significantly in the severe coagulopathy group. Furthermore the respiratory component of the SOFA score significant decreased in severe coagulopathy group compared with mild coagulopathy group.

Conclusions

rhTM administration may reduce mortality by improving organ dysfunction especially for respiratory in septic patients with severe coagulopathy.

     

Using angiogenic factors and their soluble receptors to predict organ dysfunction in patients with disseminated intravascular coagulation associated with severe trauma

ABSTRACT: INTRODUCTION: Disseminated intravascular coagulation (DIC) is characterized by the concomitant activation of coagulofibrinolytic disorders and systemic inflammation associated with endothelial dysfunction-induced microvascular permeability. Angiogenic factors, including vascular endothelial growth factor (VEGF), angiopoietin (Ang), and their receptors, play crucial roles in angiogenesis and microvascular permeability. The aim of the study was to assess the relationship between angiogenic factors, their soluble receptors and organ dysfunction associated with DIC after severe trauma. MATERIALS AND METHODS: A total of 57 patients with severe trauma were divided into two subgroups; 30 DIC patients and 27 non-DIC patients. The DIC was diagnosed based on the Japanese Association for Acute Medicine (JAAM) DIC and the International Society on Thrombosis and Haemostasis (ISTH) overt DIC criteria. The serum levels of angiogenic factors were measured at the time of admission (Day 1), Day 3 and Day 5. This study compared levels of these angiogenic factors between the two DIC groups, and evaluated their predictive value for organ dysfunction. RESULTS: DIC patients, especially those with ISTH DIC, showed higher Sequential Organ Failure Assessment (SOFA) scores and lactate levels. There were lower levels of VEGF, Ang1 and the soluble Tie2 in the ISTH DIC patients than the non-DIC patients. The levels of soluble VEGF receptor-1 (sVEGFR1), Ang2 and the Ang2/Ang1 ratio in the ISTH DIC patients were higher than in non-DIC patients. The relationship between the presence of massive transfusion and angiogenic factors indicated the same results. The levels of sVEGFR1, Ang2 and the Ang2/Ang1 ratio correlated with the SOFA scores. In particular, sVEGFR1 and Ang2 were independent predictors of an increase in the SOFA score. The lactate levels independently predicted increases in the levels of sVEGFR1 and Ang2. The decrease in the platelet counts also independently predicted the increase in Ang2 levels in DIC patients. CONCLUSIONS: Angiogenic factors and their soluble receptors, particularly sVEGFR1 and Ang2, are considered to play pivotal roles in the development of organ dysfunction in DIC associated with severe trauma. DIC-induced tissue hypoxia and platelet consumption may play crucial roles in inducing sVEGFR1 and Ang2, and in determining the prognosis of the severity of organ dysfunction.     

小剂量肝素治疗危重儿伴全身炎症反应综合征的疗效观察

目的：观察小剂量肝素持续静脉滴注对伴全身炎症反应综合征（SIRS）的危重儿临床疗效及患儿血小板计数、C反应蛋白（CRP）水平变化。方法：对符合诊断标准的115例SIRS患儿随机分为间断用药组和持续用药组，观察两组临床效果及血小板计数及CRP水平变化。结果：两组治疗前后比较，持续用药组，血小板计数均明显升高，CRP水平均明显下降（均P〈0．05），与间断用药组相比，持续用药组多脏器功能不全（MODS）发生率有显著降低（P〈0．05）．SIRS的持续时间缩短。结论：持续小剂量肝索静脉滴注疗效优于间断用药，可以明显改善危重儿的预后。     

Prognostic value of a simple evolving disseminated intravascular coagulation score in patients with severe sepsis

OBJECTIVE: We postulated that the coagulopathy initiated by the inflammatory response to severe sepsis would be reflected by changes in the platelet count and prothrombin time that convey prognostic information. To examine this hypothesis, we looked at the utility of a simple evolving disseminated intravascular coagulation (DIC) score that awarded 1 point for each of the following: a) an absolute platelet count <100 x 10/L; b) a prothrombin time >15.0 secs; c) a 20% decrease in platelets; and d) a >0.3-sec increase in prothrombin time in predicting outcome in patients with severe sepsis. DESIGN: Prospective observational study. SETTING: Intensive care units of university medical center. PATIENTS: Patients were 163 critically ill severe sepsis patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were clinically classified as having capillary leak syndrome (n = 24), multiple organ failure with death from sepsis (n = 37), or multiple organ failure with recovery (n = 57) or as well (n = 45) if they showed rapid improvement in their modified Multiple Organ Dysfunction Syndrome (MODS) score (which did not score for thrombocytopenia). Patients with capillary leak syndrome had the highest Acute Physiology and Chronic Health Evaluation II score, modified MODS, and prothrombin time and the lowest platelet counts, whereas well patients had the most normal values. The simple evolving DIC score increased with worsening clinical class and was associated with worsening organ failure (increased modified MODS). Mortality rate increased from 10% for a simple evolving score of 0 to 73% for a score of 4 (p < .01). Overall, 86% of those with a score < or =1 survived, whereas 85% of those with a score of > or =2 developed multiple organ failure and half of them died from sepsis. CONCLUSIONS: The simple evolving DIC score calculated in the first 48 hrs from two readily available global coagulation markers appears to reflect the severity of the underlying disorder. It can be easily calculated at the bedside and provides useful prognostic information for the patient with severe sepsis.     

A multicenter, prospective validation of disseminated intravascular coagulation diagnostic criteria for critically ill patients: comparing current criteria

OBJECTIVES: To validate scoring algorithm criteria established by the Japanese Association for Acute Medicine (JAAM) for disseminated intravascular coagulation (DIC) and to evaluate its diagnostic property by comparing the two leading scoring systems for DIC, from the Japanese Ministry of Health and Welfare (JMHW) and International Society on Thrombosis and Haemostasis (ISTH). DESIGN: Prospective, multicenter study during a 3-month period. SETTING: General critical care center in a tertiary care hospital. Patients: Two hundred seventy-three patients with platelet counts<150x109/L were enrolled. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The JAAM, JMHW, and ISTH DIC scoring algorithms were prospectively applied within 12 hrs of patients meeting the inclusion criteria (day 0) to days 1-3, by global coagulation tests. The numbers of systemic inflammatory response syndrome (SIRS) criteria and Sequential Organ Failure Assessment (SOFA) scores were determined simultaneously. Mortality associated with any cause was also assessed 28 days after the enrollment. All global coagulation tests and SIRS criteria adopted in the JAAM criteria and their cutoff points were validated with use of SOFA scores and mortality rate. DIC diagnostic rate of the JAAM DIC scoring system was significantly higher than that of the other two criteria (p<.001). The JAAM DIC algorithm was the most sensitive for early diagnosis of DIC (p<.001). Patients who fulfilled the JAAM DIC criteria included almost all those whose DIC was diagnosed by the JMHW and ISTH scoring systems. The JAAM DIC scores showed significant correlation with SOFA scores ([rho]=0.499; p<.001). SOFA score and mortality rate worsened in accordance with an increase in the JAAM DIC score. Fibrinogen criteria had little effect in predicting outcome for the DIC patients, and a total score of 4 points in the JAAM scoring system without fibrinogen was closely related to poor prognosis. According to the results, we revised the JAAM criteria by excluding fibrinogen and confirmed that the DIC diagnostic properties of original criteria remained unchanged in the revised JAAM criteria. CONCLUSIONS: The JAAM scoring system has an acceptable property for the diagnosis of DIC. The scoring system identified most of the patients diagnosed by the JMHW and ISTH criteria. Revised JAAM DIC criteria preserved all properties of the original criteria for DIC diagnosis. The revised scoring system can be useful for selecting DIC patients for early treatment in a critical care setting.     

Glasgow Coma Scale score dominates the association between admission Sequential Organ Failure Assessment score and 30-day mortality in a mixed intensive care unit population

Objective

The Sequential Organ Failure Assessment (SOFA) score, a measure of multiple-organ dysfunction syndrome, is used to predict mortality in critically ill patients by assigning equally weighted scores across 6 different organ systems. We hypothesized that specific organ systems would have a greater association with mortality than others.

Design

We retrospectively studied patients admitted over a period of 4.2 years to a mixed-profile intensive care unit (ICU). We recorded age and comorbidities, and calculated SOFA organ scores. The primary outcome was 30-day all-cause mortality. We determined which organ subscores of the SOFA score were most associated with mortality using multiple analytic methods: random forests, conditional inference trees, distanced-based clustering techniques, and logistic regression.

Setting

A 24-bed mixed-profile adult ICU that cares for medical, surgical, and trauma (level 1) patients at an academic referral center.

Patients

All patients' first admission to the study ICU during the study period.

Measurements and Main Results

We identified 9120 first admissions during the study period. Overall 30-day mortality was 12%. Multiple analytical methods all demonstrated that the best initial prediction variables were age and the central nervous system SOFA subscore, which is determined solely by Glasgow Coma Scale score.

Conclusions

In a mixed population of critically ill patients, the Glasgow Coma Scale score dominates the association between admission SOFA score and 30-day mortality. Future research into outcomes from multiple-organ dysfunction may benefit from new models for measuring organ dysfunction with special attention to neurologic dysfunction.     

Comparison of procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations at different SOFA scores during the course of sepsis and MODS

OBJECTIVES: The relation of procalcitonin (PCT) plasma concentrations compared with C-reactive protein (CRP) was analyzed in patients with different severity of multiple organ dysfunction syndrome (MODS) and systemic inflammation. PATIENTS AND METHODS: PCT, CRP, the sepsis-related organ failure assessment (SOFA) score, the Acute Physiology, Age, Chronic Health Evaluation (APACHE) II score and survival were evaluated in 40 patients with systemic inflammation and consecutive MODS over a period of 15 days. RESULTS: Higher SOFA score levels were associated with significantly higher PCT plasma concentrations (SOFA 7-12: PCT 2.62 ng/ml, SOFA 19-24: PCT 15.22 ng/ml) (median), whereas CRP was elevated irrespective of the scores observed (SOFT 7-12: CRP 131 mg/l, SOFT 19-24: CRP 135 mg/l). PCT of non-surviving patients was initially not different from that of survivors but significantly increased after the fourth day following onset of the disease, whereas CRP was not different between both groups throughout the whole observation period. CONCLUSIONS: Measurement of PCT concentrations during multiple organ dysfunction syndrome provides more information about the severity and the course of the disease than that of CRP. Regarding the strong association of PCT and the respective score systems in future studies we recommend evaluation also of the severity of inflammation and MODS when PCT concentrations were compared between different types of disease.     

Time course of platelet counts in critically ill patients

BACKGROUND: Although thrombocytopenia in the intensive care unit (ICU) is associated with a poorer outcome, the precise relationship between the time course of platelet counts and the mortality rate has not been well defined. OBJECTIVE: To describe the time course of the platelet count in relation to the mortality rate in critically ill patients. DESIGN: Substudy of a prospective, multicenter, observational cohort analysis. SETTING: Forty ICUs in 16 countries from Europe, America, and Australia. PATIENTS: Data were collected from all ICU admissions in a 1-month period, excluding patients younger than 12 yrs old and those who stayed in the ICU for <48 hrs after uncomplicated surgery. A total of 1,449 critically ill patients were enrolled, including 257 who stayed in the ICU for >2 wks. INTERVENTIONS: None. MEASUREMENTS: Platelet counts were collected daily throughout the ICU stay, together with other measures of organ dysfunction. Thrombocytopenia was defined as a platelet count of <150 x 103/mm3. A relative increase in platelet count was defined as a 25% increase above the admission value, together with an absolute platelet count of > or =150 x 103/mm3. MAIN RESULTS: For the entire population, the platelet count was lower in the 313 nonsurvivors than in the 1,131 survivors throughout the ICU course. Of the 257 patients who stayed in the ICU for >2 wks, 187 (64%) survived. The platelet count decreased significantly in the first days after admission to reach a nadir on day 4 in both survivors and nonsurvivors. In the survivors, the platelet count returned to the admission value by the end of the first week and continued to rise to become significantly greater than the admission value by day 9. In the nonsurvivors, the platelet count also returned to the admission value after 1 wk, but there was no subsequent increase in platelet count. A total of 138 (54%) patients had thrombocytopenia on day 4, and these patients had a greater mortality rate than the other patients (33% vs. 16%; p <.05). On day 14, 51 (20%) patients had thrombocytopenia, and these patients had a greater mortality rate than the other patients (66% vs. 16%; p <.05). Thrombocytopenia was less common on day 14 than on day 4 (20% vs. 54%; p <.05), but the mortality rate was greater in the thrombocytopenic patients on day 14 than those who were thrombocytopenic on day 4 (66% vs. 33%; p <.05). The ICU mortality rate of nonthrombocytopenic patients on day 14 was also significantly lower in patients with, than without, a relative increase in platelet count on day 14 (11% vs. 30%; p <.05). CONCLUSION: Platelet count changes in the critically ill have a biphasic pattern that is different in survivors and nonsurvivors. Late thrombocytopenia is more predictive of death than early thrombocytopenia. A relative increase in platelet count after thrombocytopenia was present in survivors but not in nonsurvivors. Although a single measured platelet count is of little value for predicting outcome, changes in platelet count over time are related to patient outcome.     

严重烧伤患者全身炎症反应综合征与器官功能不全的关系——全身炎症反应综合征评分的意义

目的：评价严重烧伤患者全身炎症反应综合征（ＳＩＲＳ）以及诊断ＳＩＲＳ的４ 个要素对器官功能不全的影响。方法：对严重烧伤患者诊断ＳＩＲＳ的４ 个要素进行评分,并与器官功能评分结果进行逐步多元回归分析。对不同诊断标准的ＳＩＲＳ发生时间与器官功能评分进行相关分析。结果：诊断ＳＩＲＳ的４ 个要素中,对器官功能不全的影响从大到小依次是呼吸频率、心率、体温和白细胞计数。严重烧伤患者不同诊断标准的ＳＩＲＳ发生时间均与器官功能不全的发生显著相关。尤其以满足３个要素的发生时间与器官功能不全评分的相关系数最高。结论：诊断ＳＩＲＳ的不同要素对严重烧伤患者预后的判断有不同价值,严重烧伤患者ＳＩＲＳ的持续时间以及严重程度影响器官功能不全的发生。     

Daily organ-system failure for diagnosis of persistent intra-abdominal sepsis after postoperative peritonitis

OBJECTIVE: To evaluate the time-course of two organ failure scores (SOFA and Goris) after surgery for postoperative peritonitis in critically ill patients according to the persistence/nonpersistence of intraabdominal sepsis (IAS). DESIGN: Retrospective study. PATIENTS: Sixty-two consecutive patients (SAPSII = 38+/-14) admitted in the surgical ICU. METHODS: Patients were classified according to the persistence of IAS (IAS+, n=36) confirmed by a second laparotomy or the lack of IAS (IAS-, n=26) assessed by a favorable 30-day evolution without reintervention. Scores were calculated daily from day 0 preoperatively to postoperative day 5. RESULTS: In both groups, SOFA scores were higher on day 1 when compared to day 0 (8.3+/-3.1 vs 6.1+/-3.7 in the IAS+ group and 5.2+/-3.4 vs 2.7+/-2.7 in the IAS- group). In the IAS- patients, the SOFA score displayed a decrease starting on day 2 when compared to day 1 (4.4+/-3.6 vs 5.2+/-3.4, P=0.03). In contrast, in the IAS+ patients, the SOFA score remained unchanged until day 5. The time course of the Goris score was strictly similar to the SOFA scores. CONCLUSION: In critically ill patients with postoperative peritonitis, the postoperative time course of the SOFA and the Goris organ failure scores was different between patients with or without intra-abdominal persistent sepsis. The lack of improvement of one of these scores on postoperative day 2 may suggest persistent intraabdominal sepsis and supports the need for a new surgical exploration.     

Multiple organ dysfunction associated with severe acute pancreatitis

OBJECTIVE: To compare three different multiple organ dysfunction scores in predicting hospital mortality rates and to discover which one best assesses organ dysfunction/failure in patients with severe acute pancreatitis in a general intensive care unit. DESIGN: Retrospective, observational study. SETTING: Surgical department and a ten-bed general intensive care unit in a tertiary care hospital. PATIENTS: Among the 178 consecutive patients admitted to the surgical department with severe acute pancreatitis from 1994 to 1998, 113 patients treated in the general intensive care unit underwent study. INTERVENTIONS: None. MEASUREMENT AND MAIN RESULTS: Clinical and laboratory data were collected during a period of 35 days. Acute Physiology and Chronic Health Evaluation (APACHE) II, Multiple Organ Dysfunction (MOD) score, Sequential Organ Failure Assessment (SOFA) score, and Logistic Organ Dysfunction (LOD) score were calculated and compared regarding hospital mortality rate. In addition, daily maximum score and a total maximum score (sum of the highest values for each organ dysfunction) were calculated for all three scores. The area under the receiver operating characteristic curve was used as a measure of accuracy of the scores. The highest accuracy was revealed with daily maximum scores with the area under the receiver operating characteristic curve 0.847 for SOFA, 0.844 for MOD, and 0.836 for LOD. According to the maximum SOFA score, the highest mortality rate was associated with liver (83%, p <.001) and renal (63%, p <.001) failures. The mortality ratio with two organ failures ranged from 50% to 91%. The highest mortality rate (91%) was for a combination of hepatic and renal failure. In multiple logistic regression analysis, only hepatic, renal, and cardiovascular failure and previous cardiovascular medication were independent risk factors for hospital mortality. CONCLUSION: In patients with severe acute pancreatitis, organ dysfunction scores (MOD, SOFA, LOD) show good accuracy, comparable with APACHE II in predicting hospital mortality. The maximum daily organ dysfunction scores were simple and useful in assessing multiple organ dysfunction and in predicting hospital mortality rates of patients with severe acute pancreatitis.     

A randomized,controlled, multicenter trial of the effects of antithrombin on disseminated intravascular coagulation in patients with sepsis

Introduction

To test the hypothesis that the administration of antithrombin concentrate improves disseminated intravascular coagulation (DIC), resulting in recovery from DIC and better outcomes in patients with sepsis, we conducted a prospective, randomized controlled multicenter trial at 13 critical care centers in tertiary care hospitals.

Methods

We enrolled 60 DIC patients with sepsis and antithrombin levels of 50 to 80% in this study. The participating patients were randomly assigned to an antithrombin arm receiving antithrombin at a dose of 30 IU/kg per day for three days or a control arm treated with no intervention. The primary efficacy end point was recovery from DIC on day 3. The analysis was conducted with an intention-to-treat approach. DIC was diagnosed according to the Japanese Association for Acute Medicine (JAAM) scoring system. The systemic inflammatory response syndrome (SIRS) score, platelet count and global markers of coagulation and fibrinolysis were measured on day 0 and day 3.

Results

Antithrombin treatment resulted in significantly decreased DIC scores and better recovery rates from DIC compared with those observed in the control group on day 3. The incidence of minor bleeding complications did not increase, and no major bleeding related to antithrombin treatment was observed. The platelet count significantly increased; however, antithrombin did not influence the sequential organ failure assessment (SOFA) score or markers of coagulation and fibrinolysis on day 3.

Conclusions

Moderate doses of antithrombin improve DIC scores, thereby increasing the recovery rate from DIC without any risk of bleeding in DIC patients with sepsis.

Trial registration

UMIN Clinical Trials Registry (UMIN-CTR) UMIN000000882     

Usefulness of suPAR as a biological marker in patients with systemic inflammation or infection: a systematic review

Purpose

Systemic levels of soluble urokinase-type plasminogen activator receptor (suPAR) positively correlate with the activation level of the immune system. We reviewed the usefulness of systemic levels of suPAR in the care of critically ill patients with sepsis, SIRS, and bacteremia, focusing on its diagnostic and prognostic value.

Methods

A PubMed search on suPAR was conducted, including manual cross-referencing. The list of papers was narrowed to original studies of critically ill patients. Ten papers on original studies of critically ill patients were identified that report on suPAR in sepsis, SIRS, or bacteremia.

Results

Systematic levels of suPAR have little diagnostic value in critically ill patients with sepsis, SIRS, or bacteremia. Systemic levels of suPAR, however, have superior prognostic power over other commonly used biological markers in these patients. Mortality prediction by other biological markers or severity-of-disease classification system scores improves when combining them with suPAR. Systemic levels of suPAR correlate positively with markers of organ dysfunction and severity-of-disease classification system scores. Finally, systemic levels of suPAR remain elevated for prolonged periods after admission and only tend to decline after several weeks. Notably, the type of assay used to measure suPAR as well as the age of the patients and underlying disease affect systemic levels of suPAR.

Conclusions

The diagnostic value of suPAR is low in patients with sepsis. Systemic levels of suPAR have prognostic value, and may add to prognostication of patients with sepsis or SIRS complementing severity-of-disease classification systems and other biological markers.     

New disseminated intravascular coagulation score: A useful tool to predict mortality in comparison with Acute Physiology and Chronic Health Evaluation II and Logistic Organ Dysfunction scores

OBJECTIVE: To compare the performance of a coagulation score-the new scoring system for diagnosing disseminated intravascular coagulation (DIC)-with the Acute Physiology and Chronic Health Evaluation (APACHE) II and Logistic Organ Dysfunction score in mortality prediction. DESIGN: Single-center retrospective study. SETTING: Medical intensive care unit of the University of Munich. PATIENTS: A total of 797 patients admitted to the intensive care unit between January 1, 1996, and January 1, 2001. METHODS: A retrospective analysis of all patients was done if the coagulation variables d-dimer, platelet count, fibrinogen, and prothrombin index were available within the first 12 hrs after admission. Patients with missing values, fibrinolytic therapy, or unknown survival status were excluded from analysis. As a marker of fibrin generation, d-dimer was measured and integrated into the scoring system for DIC together with prothrombin time, fibrinogen, and platelet count. A coagulation score was calculated in analogy with the scoring system for DIC in patients not typically developing DIC. MEASUREMENTS AND RESULTS: Overall, the mean result of the scoring system for DIC was 2.2 points. An increasing scoring system for DIC was associated with increasing mortality in patients with serious infections. Use of the scoring system for DIC in addition to the APACHE II score helps to predict mortality better than the APACHE II score alone, especially in patients with infections. The Cox regression analysis showed that the DIC and APACHE II scores correlated independently with survival time with a greater effect of the DIC score than the APACHE II or the Logistic Organ Dysfunction score. Similar results were obtained using the coagulation score in patients with cardiocirculatory diseases. CONCLUSION: Our retrospective data suggest that a combination of the APACHE II score and the scoring system for DIC predicts mortality in critically ill patients with available variables better than the APACHE II score alone. This effect is most pronounced among patients with active infection. These results of our retrospective analysis have to be confirmed in a prospective study.     

Tissue factor pathway inhibitor response does not correlate with tissue factor-induced disseminated intravascular coagulation and multiple organ dysfunction syndrome in trauma patients

OBJECTIVE: To determine the precise relationship between tissue factor and tissue factor pathway inhibitor (TFPI) after trauma, as well as to test the hypothesis that low TFPI levels are not sufficient to prevent tissue factor-dependent intravascular coagulation, leading to multiple organ dysfunction syndrome (MODS). DESIGN: Prospective, observational cohort study. SETTING: Emergency room and intensive care unit in a university hospital. PATIENTS: Thirty-three trauma patients, 18 with disseminated intravascular coagulation (DIC) and 15 without DIC were studied. Ten normal, healthy volunteers served as control subjects. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Antigen concentration of tissue factor and TFPI, and global parameters of coagulation and fibrinolysis were measured on the day of admission, and on days 1-4 after admission. The number of systemic inflammatory response syndrome (SIRS) criteria that patients met and the DIC score were determined, simultaneously. The results of these measurements, incidence of MODS, and outcome were compared between the DIC patients and those without DIC. In the DIC patients, significantly higher tissue factor levels (p =.0049) and lower platelet counts (p =.0016) were found compared with the non-DIC patients and control subjects. However, the TFPI values remained at normal levels during the study period. No correlation was found between the peak levels of tissue factor and TFPI. The mean duration of SIRS and the maximum number of the SIRS criteria being met by the patients in the DIC group were statistically longer and higher than those in the non-DIC patients. The incidence of MODS and the number of the dysfunctioning organs were higher in the DIC patients compared with those in the non-DIC patients, and the DIC patients had a poor outcome. CONCLUSIONS: We systematically elucidated the relationship between tissue factor and TFPI in post-trauma patients. Highly activated tissue factor-dependent coagulation pathway is not sufficiently prevented by the normal TFPI levels in patients with DIC. The DIC associated with thrombotic and inflammatory responses causes MODS, and leads to poor outcome in post-trauma patients.     

冠脉搭桥病人术后器官功能评分和预后分析

目的　采用序贯器官衰竭估计 (SOFA)评价急诊和择期冠状动脉搭桥 (CABG)术后的器官功能并对预后进行分析。方法　急诊CABG和择期CABG病人各 4 2例 ,进行回顾性分析。根据SOFA评分标准 ,确定术后在重症监护病房 (ICU)期间每天的器官功能评分 ,比较两组病人SOFA总分 (totalSOFAscore) ,分析总的最高SOFA评分 (TMS)以及各器官最差SOFA评分与预后的关系。结果　急诊组的死亡率高于择期组 (P <0 0 5 )。急诊组术后前 5d的SOFA总分均高于择期组 (P <0 0 1) ,死亡病例的TMS、除肝脏外的器官最差评分均高于存活病例 (P <0 0 5或 P <0 0 1) ,Logistic回归分析发现呼吸、心血管和中枢神经系统与死亡相关 (P <0 0 1)。急诊组存活病例的TMS高于择期组 (P <0 0 1) ,心血管支持时间和ICU停留时间较长 (P <0 0 5或P <0 0 1)。存活病例的ICU停留时间和TMS之间存在相关性 ,相关系数为 0 4 5 2 (P <0 0 1)。结论　SOFA是反映CABG病人预后的指标。急诊CABG术后器官功能评分较高 ,预后较差 ,与呼吸、心血管和中枢神经系统功能障碍有关。     

Risk factors for clinically important upper gastrointestinal bleeding in patients requiring mechanical ventilation. Canadian Critical Care Trials Group

OBJECTIVE: To evaluate the incidence and risk factors for clinically important upper gastrointestinal bleeding in critically ill patients requiring mechanical ventilation. DESIGN: In duplicate, blinded adjudicators determined the presence of clinically important gastrointestinal bleeding using a priori criteria, evaluating relevant clinical, laboratory, and diagnostic data. Cox proportional hazards regression analyses were used to examine baseline and time-dependent risk factors for bleeding. SETTING: Sixteen university-affiliated intensive care units (ICUs) in Canada. PATIENTS: A total of 1,077 critically ill ICU patients ventilated for at least 48 hrs. INTERVENTIONS: Patients were randomized to stress ulcer prophylaxis with intravenous ranitidine or nasogastric sucralfate; otherwise, management was at the discretion of the ICU team. MEASUREMENTS AND MAIN RESULTS: Demographic data included patient characteristics, Acute Physiology and Chronic Health Evaluation II score, and multiple organ dysfunction (MOD) score. Each day in the ICU, physiologic measurements including MOD score, feeding, and other treatment variables were recorded. The significant risk factors for upper gastrointestinal bleeding in the univariable analyses were low platelet count, maximum serum creatinine, maximum MOD score, maximum pulmonary component of the MOD score, maximum hepatic component of the MOD score, maximum renal component of the MOD score, enteral nutrition, and stress ulcer prophylaxis with ranitidine. The only independent predictors of bleeding in the multivariable analysis were maximum serum creatinine (relative risk = 1.16 [95% confidence interval = 1.02-1.32]), enteral nutrition (relative risk = 0.30 [95% confidence interval = 0.13-0.67]), and ranitidine administration (relative risk = 0.39 [95% confidence interval = 0.17-0.83]). CONCLUSIONS: In critically ill ventilated patients, renal failure was independently associated with an increased risk of clinically important gastrointestinal bleeding, whereas enteral nutrition and stress ulcer prophylaxis with ranitidine conferred significantly lower bleeding rates.     

Clopidogrel resistance "Live" – the risk of stent thrombosis should be evaluated before procedures

Background

Endothelial cell dysfunction, by promoting fibrin deposition, has been implicated in the development of multiple organ failure. Altered fibrinolysis during inflammation may participate in microvascular alterations. We sought to determine whether plasma fibrinolysis was related to the severity of organ dysfunction and/or to the levels of von Willebrand factor (vWF antigen), as a marker of endothelium dysfunction, in critically ill patients.

Methods

Forty-nine consecutive patients admitted to an adult medico-surgical intensive care unit (ICU) with (18) or without sepsis (31) were included. C-reactive protein and vWF levels were measured on ICU admission and plasma fibrinolysis was assessed by the Euglobulin Clot Lysis Time (ECLT). The sequential organ failure assessment (SOFA) score and the simplified acute physiology score (SAPS) II were calculated on admission.

Results

ECLT was significantly longer in septic than in non-septic patients [1033 min (871–1372) versus 665 min (551–862), p = 0.001]. There were significant correlations between ECLT and C-reactive protein (CRP) concentrations (r = 0.78, p < 0.001) and the Sequential Organ Failure Assessment (SOFA) score (r = 0.39, p = 0.006). The level of vWF was not correlated with the ECLT (r = -0.06, p = 0.65) or the SOFA score (r = -0.02, p = 0.88).

Conclusion

ECLT measurement at admission could be a marker of organ dysfunction and a prognostic indicator in critically ill patients.     

Evaluation of the SOFA score: a single-center experience of a medical intensive care unit in 303 consecutive patients with predominantly cardiovascular disorders

Objective: To evaluate the use of the Sequential Organ Failure Assessment (SOFA) score, the total maximum SOFA (TMS) score, and a derived variable, the ΔSOFA (TMS score minus total SOFA score on day 1) in medical, cardiovascular patients as a means for describing the incidence and severity of organ dysfunction and the prognostic value regarding outcome. Design: Prospective, clinical study. Setting: Medical intensive care unit in a university hospital. Patients: A total of 303 consecutive patients were included (216 men, 87 women; mean age 62 ± 12.6 years; SAPS II 26.2 ± 12.7). They were evaluated 24 h after admission and thereafter every 24 h until ICU discharge or death between November 1997 and March 1998. Readmissions and patients with an ICU stay shorter than 12 h were excluded. Main outcome measure: Survival status at hospital discharge, incidence of organ dysfunction/failure. Interventions: Collection of clinical and demographic data and raw data for the computation of the SOFA score every 24 h until ICU discharge. Measurements and main results: Length of ICU stay was 3.7 ± 4.7 days. ICU mortality was 8.3 % and hospital mortality 14.5 %. Nonsurvivors had a higher total SOFA score on day 1 (5.9 ± 3.7 vs. 1.9 ± 2.3, p < 0.001) and thereafter until day 8. High SOFA scores for any organ system and increasing number of organ failures (SOFA score ≥ 3) were associated with increased mortality. Cardiovascular and neurological systems (day 1) were related to outcome and cardiovascular and respiratory systems, and admission from another ICU to length of ICU stay. TMS score was higher in nonsurvivors (1.76 ± 2.55 vs. 0.58 ± 1.39, p < 0.01), and ΔSOFA/total SOFA on day 1 was independently related to outcome. The area under the receiver-operating characteristic curve was 0.86 for TMS, 0.82 for SOFA on day 1, and 0.77 for SAPS II. Conclusions: The SOFA, TMS, and ΔSOFA scores provide the clinician with important information on degree and progression of organ dysfunction in medical, cardiovascular patients. On day 1 both SOFA score and TMS score had a better prognostic value than SAPS II score. The model is closely related to outcome and identifies patients who are at increased risk for prolonged ICU stay. Received: 6 August 1999 Final revision received: 3 January 2000 Accepted: 28 March 2000