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PubMed2006

High-dose antithrombin III in the treatment of severe sepsis in patients with a high risk of death: efficacy and safety.

OBJECTIVE: To explore if patients with severe sepsis and with a predicted high risk of death (according to the Simplified Acute Physiology Score II) might have a treatment benefit from high-dose antithrombin III. DESIGN: Subgroup analysis of a randomized, placebo-controlled, double-blind, prospective phase III study. SETTING: Unifactorial and multifactorial reanalysis of prospectively defined populations from the KyberSept trial. PATIENTS: We studied 1,008 patients (43.6% of the overall intention-to-treat population, n = 2,314) with a predicted mortality rate of 30-60% at study entry as defined by the Simplified Acute Physiology Score II. INTERVENTIONS: Patients were randomized in a 1:1 fashion to receive either high-dose antithrombin III (30,000 IU intravenously over the period of 4 days) or placebo. MEASUREMENTS AND MAIN RESULTS: In a Kaplan-Meier analysis of patients with a predicted mortality of 30-60%, the survival time when followed up for 90 days after admission was increased in the high-dose antithrombin III group compared with placebo (p = .04). If heparin was avoided during the 4-day treatment phase with high-dose antithrombin III (n = 140) or placebo (n = 162), the treatment effect appeared to be even more pronounced: 28-day mortality rate, 35.7% vs. 44.4% (risk ratio, 0.804; 95% confidence interval, 0.607-1.064); 56-day mortality rate, 39.9% vs. 52.2% (risk ratio, 0.764; 95% confidence interval, 0.593-0.984); 90-day mortality rate, 42.8% vs. 55.1% (risk ratio, 0.776; 95% confidence interval, 0.614-0.986). Like in the overall population, the percentage with any bleeding was increased in patients receiving high-dose antithrombin III compared with placebo. Survival rates were in favor of high-dose antithrombin III in patients both with and without bleeding complications. CONCLUSIONS: Treatment with high-dose antithrombin III may increase survival time up to 90 days in patients with severe sepsis and high risk of death. This benefit may even be stronger when concomitant heparin is avoided.

APACHE↗

PubMed2000

Antithrombin III and local serum application: adjuvant therapy in peritonitis.

BACKGROUND: Patients with diffuse peritonitis show an overall mortality of about 20%, probably caused by the breakdown of local defence mechanisms combined with a systemic outspread of bacteria and toxins, which often results in sepsis syndrome. DESIGN: In a prospective, randomized, controlled study 50 patients with diffuse secondary peritonitis were included. Patients in the therapy group were treated with an adjuvant medication consisting of a continuous intravenous infusion of antithrombin III and two intraperitoneal instillations of fresh frozen human donor serum. The aim of the study was the reduction of mortality and incidence of multiple organ failure. RESULTS: Mean antithrombin III plasma levels in the therapy group were raised above 140% for 4 days and were significantly higher than in the control group. With the intraperitoneal application of fresh frozen serum and antithrombin III opsonic capacity as well as thrombin, inhibitory activity in the exudate could be significantly elevated over 2 days. The 90-day-mortality rate was 6/26 (23%) in the control group and 6/24 (25%) in the therapy group. Although no improvement of mortality was achieved, a slight but not significant reduction of the severity of the multiple organ failure was seen. CONCLUSIONS: The chosen therapeutic approach was feasible and showed no side-effects. Yet, neither mortality nor multiple organ failure were significantly improved by the applied short-term adjuvant therapy. Thus, for future trials in severely-ill patients a longer treatment period and/or combinations of antithrombin III with other anti-inflammatory agents should be considered.

APACHE↗

PubMed1998

Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis.

OBJECTIVES: To evaluate the safety and potential efficacy of antithrombin III (AT III) in reducing mortality in patients with severe sepsis. DESIGN: Prospective, randomized, placebo-controlled, double-blind, phase II, multicenter, multinational clinical trial. SETTING: Seven academic medical center intensive care units (ICU) in Belgium, Denmark, the Netherlands, Norway and Sweden. PATIENTS: 42 patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III or placebo. INTERVENTIONS: Patients received either an intravenous loading dose of 3000 IU AT III followed by a maintenance dose of 1500 IU every 12 h for 5 days or equivalent amounts of placebo. MEASUREMENTS AND RESULTS: All patients were evaluated for safety and for 30-day all-cause mortality. CONCLUSIONS: The administration of AT III was safe and well-tolerated. It was followed by a 39 % reduction in 30-day all-cause mortality (NS). The reduction in mortality was accompanied by a considerably shorter stay in the ICU. Patients treated with AT III exhibited a better performance in overall severity of illness and organ failure scores (Acute Physiology and Chronic Health Evaluation II, multiple organ failure, organ system failure), which was noticeable soon after initiation of treatment. Patients treated with AT III demonstrated a better resolution of pre-existing organ failures and a lower incidence of new organ failures during the observation period. A meta-analysis comprising this and two other double-blind, placebo-controlled trials with AT III with a total of 122 patients suffering from severe sepsis confirms the positive trend. The results of the meta-analysis demonstrate a 22.9 % reduction in 30-day all-cause mortality in patients treated with AT III. Although still too small to be confirmative, the meta-analysis clearly points to the fact that a sufficiently powered phase III trial is warranted to prove whether AT III has a beneficial role in the treatment of severe sepsis.

APACHE↗

PubMed1994

Use of antithrombin III in critical patients.

OBJECTIVE: To evaluate the effect of the AT III concentrates upon the clinical evolution and hemostatic parameters. DESIGN: Prospective, open, randomized trial. PATIENTS AND PARTICIPANTS: Septic and multiple trauma patients admitted to our Intensive Care Unit. SETTING: Levels of AT III below 70% were used as criteria to choose 36 patients, 20 of whom received treatment with AT III and 16 did not. INTERVENTIONS: AT III concentrates were administered at an initial dose of 60 U/kg followed by 10 U/kg every six hours. RESULTS: The administration of AT III neither contributes to alterations in haemostasis, nor the clinical evolution (evaluated according to Apache II score). CONCLUSIONS: The results suggest that the administration of AT III concentrates to critical patients with acquired low levels, but without manifest DIC, may not be justified; although further studies on a larger population are required to establish definite conclusions.

APACHE↗

PubMed1998

Antithrombin III (ATIII) replacement therapy in patients with sepsis and/or postsurgical complications: a controlled double-blind, randomized, multicenter study.

BACKGROUND: ATIII is decreased in sepsis and/or shock and its baseline value correlates with mortality. The efficacy of ATIII therapy on mortality was assessed in a selected group of patients admitted to the intensive care unit (ICU) in a double-blind, randomized, multicenter study. METHODS: 120 patients admitted to the ICU with an ATIII concentration < 70% were randomized to receive ATIII (total dose 24000 units) or placebo treatment for 5 days; 56 patients had septic shock. RESULTS: ATIII concentrations in the treated group remained constant throughout the treatment period (range 97-102%). The Kaplan-Meier analysis showed no difference in overall survival between the two groups: 50 and 46% for ATIII and placebo, respectively. Septic shock and hemodynamic support were unbalanced in the two groups at admission. Therefore the Cox analysis was carried out after adjusting for these two variables. Treatment with ATIII decreases the risk of death with an odds ratio (OR) of 0.56. Of the covariates analyzed, septic shock and the baseline multiple organ failure score were negatively associated with survival and plasma activity level was positively associated with survival with an OR of 0.97 for each 1% increase in the ATIII plasma concentration at baseline. CONCLUSIONS: The results of ATIII treatment in this population of patients suggests that replacement therapy reduces mortality in the subgroup of septic shock patients only.

APACHE↗

PubMed2003

Respiratory failure and sepsis are the major causes of ICU admissions and mortality in survivors of lung transplants.

STUDY OBJECTIVE: To identify outcome predictors and prognostic factors in long-term survivors (> 30 days post-transplant) of single-lung and double-lung transplants on readmission to the medical ICU (MICU). DESIGN: Retrospective study. SETTING: MICU of the Cleveland Clinic Foundation, a lung transplantation center. PATIENTS: As of August 2000, 210 lung transplantations have been performed at our institution. The records of 33 lung transplant recipients who required readmission to the MICU after the initial 30-day post-transplant period over a 4-year period from August 16, 1996 to August 15, 2000 were reviewed. RESULTS: Thirty-three patients had a total of 46 MICU readmissions. Twenty-seven MICU admissions (59%) were due to respiratory deterioration with mechanical ventilation (10 deaths), and 16 MICU admissions (35%) were due to the systemic inflammatory response syndrome (SIRS; 8 deaths). The MICU mortality rate was 37% per admission in our group of patients. A preadmission diagnosis of bronchiolitis obliterans syndrome was observed in 7 of 14 nonsurvivors (50%) and in 5 of 25 patients (20%) surviving to hospital discharge. CONCLUSIONS: Respiratory failure and SIRS are the predominant causes of MICU readmissions and are frequent causes of death. APACHE (acute physiology and chronic health evaluation) III scores, nonpulmonary organ system dysfunction, initial serum albumin level, and duration of mechanical ventilation are important prognostic factors.

APACHE↗

PubMed2007

Ventilator-dependent survivors of catastrophic illness transferred to 23 long-term care hospitals for weaning from prolonged mechanical ventilation.

STUDY OBJECTIVES: This multicenter study was undertaken to characterize the population of ventilator-dependent patients admitted to long-term care hospitals (LTCHs) for weaning from mechanical ventilation. DESIGN: Observational study with concurrent data collection. Characteristics of the LTCHs were also surveyed. SETTING: Twenty-three LTCHs in the United States. PATIENTS: Consecutive ventilator-dependent patients admitted over a 1-year period: March 1, 2002, to February 28, 2003. RESULTS: A total of 1,419 patients were enrolled in the Ventilation Outcomes Study. Median age of the patients was 71.8 years old (range, 18 to 97.7 years), with an equal gender distribution. The premorbid domicile was home or assisted living in 86.5%; "good" premorbid functional status (Zubrod score 0-2) was assessed in 77%. There was a history of smoking in 59% (mean, 57 +/- 42 pack-years [+/- SD]); premorbid diagnoses averaged 2.6 per patient. Patients came to the LTCH after mean of 33.8 +/- 29 days at the transferring hospital; mean time to tracheotomy was 15.0 +/- 10 days. A medical illness led to ventilator dependency in 60.8% of patients; a surgical procedure led to ventilatory dependency in 39.2%. On admission to the LTCH, the median acute physiology score of APACHE (acute physiology and chronic health evaluation) III was 35 (range, 4 to 115); > 90% of patients had at least three penetrating indwelling tubes/catheters; 42% of patients had stage 2 or higher pressure ulceration. CONCLUSIONS: This is the first multicenter study to characterize ventilator-dependent survivors of catastrophic illness admitted to the post-ICU venue of LTCHs for weaning from prolonged mechanical ventilation (PMV). Overall, our findings suggest that ventilator-dependent patients admitted to LTCHs for weaning will continue to require considerable medical interventions and treatments, owing to the burden of acute-on-chronic diseases resulting in PMV.

APACHE↗

PubMed2002

2-month mortality and functional status of critically ill adult patients receiving prolonged mechanical ventilation.

STUDY OBJECTIVES: To describe the 2-month mortality and functional status of adult patients receiving prolonged (at least 48 h) mechanical ventilation (MV), and to identify patient characteristics that are associated with 2-month mortality. DESIGN: Prospective cohort study. SETTING: Four ICUs at a tertiary-care institution. PATIENTS: Eight hundred seventeen patients who received prolonged MV. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Median age, sex distribution, and median Charlson comorbidity score of the 817 patients were 65 years, 45.8% women, and 1, respectively. The median scores on Katz Activities of Daily Living, Instrumental Activities of Daily Living Deficits, and Medical Outcomes Study Short-Form 36 surveys before hospitalization were 0, 1, and 50, respectively. Median APACHE (acute physiology and chronic health evaluation) III score and probability of hospital death for the cohort were 64 and 0.31, respectively. Median duration of MV was 9 days. Two-month mortality was 43%. Independent predictors of mortality at 2 months were age, comorbidities, and prehospital functional status. The adjusted odds of dying within 2 months increased 34% for each decade increase in age. Functional status deteriorated at 2 months compared to functional status prior to hospitalization, and 35% of the survivors were at risk for clinical depression. Among the 2-month survivors for whom the need for a caregiver was assessed, 78% had a caregiver. CONCLUSIONS: Older age, in addition to functional status and comorbidities, was associated with increased mortality at 2 months. Functional status of survivors declined at 2 months.

APACHE↗

PubMed1995

The SUPPORT prognostic model. Objective estimates of survival for seriously ill hospitalized adults. Study to understand prognoses and preferences for outcomes and risks of treatments.

OBJECTIVE: To develop and validate a prognostic model that estimates survival over a 180-day period for seriously ill hospitalized adults (phase I of SUPPORT [Study to Understand Prognoses and Preferences for Outcomes and Risks of Treatments]) and to compare this model's predictions with those of an existing prognostic system and with physicians' independent estimates (SUPPORT phase II). DESIGN: Prospective cohort study. SETTING: 5 tertiary care academic centers in the United States. PARTICIPANTS: 4301 hospitalized adults were selected for phase I according to diagnosis and severity of illness; 4028 patients were evaluated from phase II. MEASUREMENTS: A survival model was developed using the following predictor variables: diagnosis, age, number of days in the hospital before study entry, presence of cancer, neurologic function, and 11 physiologic measures recorded on day 3 after study entry. Physicians were interviewed on day 3. Patients were followed for survival for 180 days after study entry. RESULTS: The area under the receiver-operating characteristics (ROC) curve for prediction of surviving 180 days was 0.79 in phase I, 0.78 in the phase II independent validation, and 0.78 when the acute physiology score from the APACHE (Acute Physiology, Age, Chronic Health Evaluation) III prognostic scoring system was substituted for the SUPPORT physiology score. For phase II patients, the SUPPORT model had equal discrimination and slightly improved calibration compared with physician's estimates. Combining the SUPPORT model with physician's estimates improved both predictive accuracy (ROC curve area = 0.82) and the ability to identify patients with high probabilities of survival or death. CONCLUSIONS: A limited amount of readily available clinical information can provide a foundation for long-term survival estimates that are as accurate as physicians' estimates. The best survival estimates combine an objective prognosis with a physician's clinical estimate.

APACHE↗

PubMed2004

The hospital mortality of patients admitted to the ICU on weekends.

STUDY OBJECTIVES: Previous studies have suggested that patients are more likely to die in the hospital if they are admitted on a weekend than on a weekday. This study was conducted to determine whether weekend admission to the ICU increases the risk of dying in the hospital. DESIGN: Retrospective cohort study. SETTING: ICU of a single tertiary care medical center. PATIENTS: A total of 29,084 patients admitted to medical, surgical, and multispecialty ICUs from October 1994 through September 2002. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The weekend ICU admissions comprised 27.9% of all ICU admissions (8,108 ICU admissions). The overall hospital mortality rate was 8.2% (2,385 deaths). Weekend ICU admission was associated with a higher unadjusted hospital mortality rate than that for weekday ICU admission (11.3% vs 7.0%, respectively; odds ratio [OR], 1.70; 95% confidence interval [CI], 1.55 to 1.85). In multivariable analyses controlling for the factors associated with mortality such as APACHE (acute physiology and chronic health evaluation) III predicted mortality rate, ICU admission source, and intensity of treatment, no statistically significant difference in hospital mortality was found between weekend and weekday admissions in the overall study population (OR, 1.06; 95% CI, 0.95 to 1.17). For weekend ICU admissions, the observed hospital mortality rates of the medical, multispecialty, and surgical ICUs were 15.2%, 17.2%, and 6.4%, respectively, and for weekday ICU admissions the rates were 16.3%, 10.1%, and 3.5%, respectively. Subgroup analyses showed that weekend ICU admission was associated with higher adjusted hospital mortality rates than was weekday ICU admission in the surgical ICU (OR, 1.23; 95% CI, 1.03 to 1.48), but not in the medical or multispecialty ICUs. CONCLUSIONS: The overall adjusted hospital mortality rate of patients admitted to the ICU on a weekend was not higher than that of patients admitted on a weekday. However, weekend ICU admission to the surgical ICU was associated with an increased hospital mortality rate.

APACHE↗

PubMed2004

Recombinant human activated protein C in sepsis: assessing its clinical use.

Based on the results of the phase III PROWESS trial, recombinant human activated protein C (rhAPC) was approved by the Food and Drug Administration (FDA) for use in severely septic patients. Concerns regarding rhAPC's inconsistent effects, incomplete understanding of its mechanism of action, and its safety in particular subgroups were raised during the FDA's evaluation. This study attempts to assess the cost-effectiveness rhAPC by comparing its effects during recent clinical use to its prior phase III trial testing and by considering other potentially less expensive treatments with effects that may overlap those of rhAPC. In patients with similar numbers of injured organs, mortality rates may be higher with rhAPC during clinical use compared with the phase III trial. There may also be an increased risk of hemorrhage and other adverse events that necessitate early discontinuation of treatment. Many of the patients receiving rhAPC during clinical use may have otherwise been excluded from its phase III trial testing. Data from several recent phase III trials as well as a recent meta-analysis suggest that heparin and physiologic dose steroids offer substantially less expensive alternatives to rhAPC. Further phase IV testing will be required to confirm such possibilities.

APACHE↗

PubMed2005

Intensivist-to-bed ratio: association with outcomes in the medical ICU.

OBJECTIVE: With an increasing number of critical care beds, a shortage of critical care physicians, and pressure from purchasers, there is a need to define the optimal intensivist-to-ICU bed ratio. The objective of this study was to determine if there are any associations between the intensivist-to-ICU bed ratio and the outcome of patients admitted to the medical ICU. DESIGN: Retrospective cohort study. SETTING: A tertiary care medical center. PATIENTS: All critically ill patients admitted to a medical ICU between December 8, 2001, and July 14, 2003. INTERVENTIONS: None. MEASUREMENTS: Demographics, APACHE (acute physiology and chronic health evaluation) III-predicted mortality, ICU length of stay (LOS), hospital LOS, and ICU and hospital mortality rates. Four time periods based on intensivist-to-ICU bed ratios of 1:7.5, 1:9.5, 1:12, and 1:15 were identified. Regression analyses were performed to develop customized models to predict ICU and hospital LOS and mortality. The ICU LOS ratio, defined as the ratio of the observed to predicted LOS, and standardized mortality ratio (SMR) were calculated for each of the four periods. RESULTS: A total of 2,492 patients were included in the study. There was no difference in the severity of illness at the time of ICU admission among the four periods. The mean ICU LOS ratio was longer for an intensivist-to-ICU bed ratio of 1:15 compared to the other periods. The ICU and hospital SMR did not differ significantly among the four periods. CONCLUSION: Differences in intensivist-to-ICU bed ratios, ranging from 1:7.5 to 1:15, were not associated with differences in ICU or hospital mortality. However, a ratio of 1:15 was associated with increased ICU LOS.

Bed Occupancy↗

PubMed1996

Hemostatic abnormalities and the severity of illness in patients at the onset of clinically defined sepsis. Possible indication of the degree of endothelial cell activation?

OBJECTIVE: To find out whether changes within the hemostatic system are related to the severity of illness and organ failure in patients at the onset of clinically defined sepsis and to find some indications for the contribution of endothelial cell activation or perturbation to the patient's status. The following measurements were undertaken: Acute Physiology and Chronic Health Evaluation (APACHE) II score, multiple organ failure (MOF) score, plasma levels of thrombin-antithrombin III complexes (TAT), antithrombin III (AT III), protein C antigen, factor XII, and plasminogen activator inhibitor type 1 antigen (PAI-1), neopterin, and interleukin 6 (IL-6). DESIGN: A prospective case series study. SETTING: Intensive care unit (ICU) of the Department of Internal Medicine, Justus Liebig University, Giessen, Germany. PATIENTS: 28 consecutive patients (11 females, 17 males; mean age 58 years) with clinically defined sepsis. Eleven patients were admitted from the surgical ICU (9 after elective surgery, 2 after trauma surgery). The operations were done 1-26 days (mean 14 days) prior to the onset of sepsis. MAIN RESULTS: At the onset of sepsis we found elevated plasma levels of TAT, PAI-1, neopterin, and IL-6, and lowered plasma levels of AT III, factor XII, and protein Cantigen. Neopterin, PAI-1, IL-6, and factor XII showed a statistically significant correlation with the APACHE II score. The MOF score is significantly correlated with IL-6 and neopterin. The extent of hemostatic abnormalities was related to increasing levels of IL-6. CONCLUSIONS: Clinical evidence of a septic process is most likely to be preceded by activation of the hemostatic system, the vascular endothelium, and the monocyte/macrophage system. IL-6 may have a regulatory function for hemostasis in inflammation. Laboratory monitoring could be helpful in deciding whether to start early intensive therapy in patients at risk for sepsis.

Adult↗

PubMed2002

Predictive value of procalcitonin and interleukin 6 in critically ill patients with suspected sepsis.

OBJECTIVE: To evaluate the performance of procalcitonin (PCT), interleukin-6 (IL-6), C-reactive protein, leukocyte count, D-dimer, and antithrombin III at onset of septic episode and 24 h later in prediction of hospital mortality in critically ill patients with suspected sepsis. DESIGN AND SETTING: Prospective, cohort study in two university hospital intensive care units. PATIENTS: 61 critically ill patients with suspected sepsis. MEASUREMENTS AND RESULTS: The outcome measure was hospital mortality. Hospital survivors ( n=41) and nonsurvivors ( n=20) differed statistically significantly on day 1 (admission) in PCT, IL-6, SOFA score, and APACHE II score, and 24 h later in PCT, IL-6, and D-dimer values. AT III, CRP, and leukocyte count did not differ. The areas under receiver operating curves showed reasonable discriminative power (>0.75) in predicting hospital mortality only for day 2 IL-6 (0.799) and day 2 PCT (0.777) values which were comparable to that of APACHE II (0.786), and which remained the only independent predictor of mortality. CONCLUSIONS: Admission and day 2 IL-6, and day 2 PCT, and day 2 D-dimer values differed significantly between hospital survivors and nonsurvivors among critically ill patients with suspected sepsis. However, in prediction of hospital mortality, only the discriminative power of day 2 PCT and IL-6 values, and APACHE II was reasonable as judged by AUC analysis (>0.75).

APACHE↗

PubMed2001

[Spontaneous perforation of the large intestine. Resection with primary anastomosis or staged (Hartmann) procedure?].

Whereas primary resection to remove the septic focus stands undisputed in the therapy of spontaneous perforation of the colon, there is still no consensus as to whether to perform a primary anastomosis or a staged procedure (Hartmann). Prospective randomized studies comparing both concepts are lacking. Obviously these two competing therapies fit different groups of patients whose diseases differ concerning etiology, localisation and severity. Analysis of the literature of the past few years defined some criteria that help to decide when to omit primary anastomosis: MPI > 20, APACHE II score > 15, preoperative organ insufficiency, Hinchey grade III or IV and ASA score IV. In these cases a discontinuity resection is recommended. Primary resection with anastomosis and Hartmann procedure are not competing operations but situation-dependent therapeutic concepts in spontaneous colonic perforation.

Anastomosis, Surgical↗

PubMed2005

Hyperglycemia after SAH: predictors, associated complications, and impact on outcome.

BACKGROUND AND PURPOSE: Hyperglycemia is common after subarachnoid hemorrhage (SAH). The extent to which prolonged hyperglycemia contributes to in-hospital complications and poor outcome after SAH is unknown. METHODS: We studied an inception cohort of 281 SAH patients with an initial serum glucose level obtained within 3 days of SAH onset and who had at least 7 daily glucose measurements between SAH days 0 and 10. We defined mean glucose burden (GB) as the average peak daily glucose level >5.8 mmol/L (105 mg/dL). Hospital complications were recorded prospectively, and 3-month outcome was assessed with the modified Rankin scale. RESULTS: The median GB was 1.8 mmol/L (33 mg/dL). Predictors of high-GB included age > or =54 years, Hunt and Hess grade III-V, poor Acute Physiology and Chronic Health Evaluation (APACHE)-2 physiological subscores, and a history of diabetes mellitus (all P< or =0.001). In a multivariate analysis, GB was associated with increased intensive care unit length of stay (P=0.003) and the following complications: congestive heart failure, respiratory failure, pneumonia, and brain stem compression from herniation (all P<0.05). After adjusting for Hunt-Hess grade, aneurysm size, and age, GB was an independent predictor of death (odds ratio, 1.10 per mmol/L; 95% CI, 1.01 to 1.21; P=0.027) and death or severe disability (modified Rankin scale score of 4 to 6; odds ratio, 1.17 per mmol/L; 95% CI 1.07 to 1.28, P<0.001). CONCLUSIONS: Hyperglycemia after SAH is associated with serious hospital complications, increased intensive care unit length of stay, and an increased risk of death or severe disability.

Adult↗

PubMed1990

Activation and inhibition of fibrinolysis in septic patients in an internal intensive care unit.

Disseminated thrombotic processes in the microcirculation are considered to be an important cause of multiple organ failure in septic patients. Fibrinolysis is one endogenous mechanism protecting the circulation from overwhelming thrombosis. Therefore, we looked for alterations of fibrinolytic parameters (tissue plasminogen activator (t-PA), tissue plasminogen activator inhibitor (PAI), D-dimer, euglobulin-clot-lysis-time (ECLT), plasminogen, alpha 2-antiplasmin) and of some coagulation parameters (prothrombin time, fibrinogen, platelets, antithrombin III, protein C, factor XII) in clearly defined septic patients and for the relations of these values to the severity of the disease (APACHE II-score). An increase in D-dimer and t-PA-antigen was registered in all patients, while factor XII and plasminogen were decreased, indicating an activated fibrinolysis. In contrast the systemic fibrinolytic capacity of the blood was strongly inhibited: t-PA-activity was not detectable, PAI-function was elevated, the ECLT was prolonged and alpha 2-antiplasmin was normal. Coagulation was moderately activated: the platelets, antithrombin III and protein C were decreased, the prothrombin time was prolonged and fibrinogen was normal. The changes in t-PA-antigen, PAI-function, factor XII, prothrombin time and antithrombin III were significantly related to the APACHE II-score of the patients. We conclude that the activation of coagulation is accompanied by an activation of fibrinolysis in the microcirculation, but that systemically the increased inhibitors of fibrinolysis (PAI, alpha 2-antiplasmin) induce a decrease of the fibrinolytic capacity of the blood. The severity of the disease determines the extent of the alterations.

Adult↗

PubMed2000

Severity of illness scores and the outcome of acute tubular necrosis.

The outcome of patients with acute renal failure (ARF) due to acute tubular necrosis (ATN) was evaluated in this study. Two hundred and twenty-two patients with a mean age of 55.1+/-17.7 years (range 19-97 years; male 153, female 69) who developed ATN in the period from July 1991 through January 1997 were studied. Patients were divided into four groups according to their APACHE II scores at the time of the diagnosis of ATN. Group I included patients with an APACHE II score of 14 or less (n = 70), Group II with a score of 15-18 (n = 52), Group III with a score of 19-23 (n = 58), and group IV with a score of 24 or above (n = 42). The mean APACHE II score for each of the four study groups was 11+/-0.4, 16+/-0.2, 20+/-0.2, and 29+/-0.7, respectively. Patient survival was evaluated by the Kaplan-Meier analysis with censorship at 12 months. Survival rates at 180 days were 67%, 47%, 39%, and zero%, for group I through IV respectively, chi2 = 27.99, p < 0.0001, with a median survival of >365, 120, 31, and 11 days, for groups I through IV, respectively. For patients with oliguria (n = 88) survival at 180 days was 23% vs. 58% for patients without oliguria (n = 134), p < 0.0001, median survival 13 vs. 364 d. Six months survival of those who required dialysis (n = 79) was 25% vs. 58% for those whom dialysis was not needed (n = 143), p = 0.001, median survival 15 vs. 364 d, respectively. In patients with sepsis (n = 58), 6 months survival was 35% vs. 50% for those without sepsis (n = 164), p = 0.013, median survival 14 vs. 169 d. In patients who required mechanical ventilation (n = 72), 6 months survival was 17% vs. 62% for those who did not need respiratory support (n = 150), p = 0.0001, median survival 13 vs. > 365 d, respectively. Finally, 6 months survival in patients with one (kidney only), two, three, and four organ failure was 76, 30, 11, and zero percent, respectively, p = 0.0001, median survival >365, 16, 11, and 12 days, respectively. We conclude that the use of the APACHE II score for the stratification of the severity of illness could be of clinical utility in predicting mortality in patients with ATN. Other predictors of poor prognosis include the need for dialysis, the presence of oliguria, the need for mechanical ventilation, the presence of sepsis, and the number of failed organs.

APACHE↗