Treatment effects of high-dose antithrombin without concomitant heparin in patients with severe sepsis with or without disseminated intravascular coagulation

BACKGROUND: Disseminated intravascular coagulation (DIC) is a serious complication of sepsis that is associated with a high mortality. OBJECTIVES: Using the adapted International Society on Thrombosis and Haemostasis (ISTH) diagnostic scoring algorithm for DIC, we evaluated the treatment effects of high-dose antithrombin (AT) in patients with severe sepsis with or without DIC. PATIENTS AND METHODS: From the phase III clinical trial in severe sepsis (KyberSept), 563 patients were identified (placebo, 277; AT, 286) who did not receive concomitant heparin and had sufficient data for DIC determination. RESULTS: At baseline, 40.7% of patients (229 of 563) had DIC. DIC in the placebo-treated patients was associated with an excess risk of mortality (28-day mortality: 40.0% vs. 22.2%, P < 0.01). AT-treated patients with DIC had an absolute reduction in 28-day mortality of 14.6% compared with placebo (P = 0.02) whereas in patients without DIC no effect on 28-day mortality was seen (0.1% reduction in mortality; P = 1.0). Bleeding complications in AT-treated patients with and without DIC were higher compared with placebo (major bleeding rates: 7.0% vs. 5.2% for patients with DIC, P = 0.6; 9.8% vs. 3.1% for patients without DIC, P = 0.02). CONCLUSIONS: High-dose AT without concomitant heparin in septic patients with DIC may result in a significant mortality reduction. The adapted ISTH DIC score may identify patients with severe sepsis who potentially benefit from high-dose AT treatment.     

Effect of acute kidney injury on weaning from mechanical ventilation in critically ill patients

OBJECTIVES: Acute kidney injury (AKI) worsens outcome in various scenarios. We sought to investigate whether the occurrence of AKI has any effect on weaning from mechanical ventilation. DESIGN AND SETTING: Observational, retrospective study in a 23-bed medical/surgical intensive care unit (ICU) in a cancer hospital from January to December 2003. PATIENTS: The inclusion criterion was invasive mechanical ventilation for > or =48 hrs. AKI was defined as at least one measurement of serum creatinine of > or =1.5 mg/dL during the ICU stay. Patients were then separated into AKI and non-AKI patients (control group). The criterion for weaning was the combination of positive end-expiratory pressure of < or =8 cm H2O, pressure support of < or =10 cm H2O, and Fio2 of < or =0.4, with spontaneous breathing. The primary end point was duration of weaning and the secondary end points were rate of weaning failure, total length of mechanical ventilation, length of stay in the ICU, and ICU mortality. RESULTS: A total of 140 patients were studied: 93 with AKI and 47 controls. The groups were similar in regard to age, sex, and type of tumor. Diagnosis of acute lung injury/acute respiratory distress syndrome as cause of respiratory failure and Simplified Acute Physiology Score II at admission did not differ between groups. During ICU stay, AKI patients had markers of more severe disease: increased occurrence of severe sepsis or septic shock, higher number of antibiotics, and longer use of vasoactive drugs. The median (interquartile range) duration of mechanical ventilation (10 [6-17] vs. 7 [2-12] days, p = .017) and duration of weaning from mechanical ventilation (41 [16-97] vs. 21 [7-33.5] hrs, p = .018) were longer in AKI patients compared with control patients. Cox regression analysis demonstrated that a > or =85% increase in baseline serum creatinine (hazard rate, 2.30; 95% confidence interval, 1.30-4.08), oliguria (hazard rate, 2.51; 95% confidence interval, 1.24-5.08), and the number of antibiotics (hazard rate, 2.64; 95% confidence interval, 1.51-4.63) predicted longer duration of weaning. The length of ICU stay and ICU mortality rate were significantly greater in the AKI patients. After adjusting for Simplified Acute Physiology Score II, oliguria (odds ratio, 30.8; 95% confidence interval, 7.7-123.0) remained as a strong risk factor for mortality. CONCLUSION: This study shows that renal dysfunction has serious consequences in the duration of mechanical ventilation, weaning from mechanical ventilation, and mortality in critically ill cancer patients.     

Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study

OBJECTIVE: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions. DESIGN: Multiple-center, prospective epidemiologic study. SETTING: Fourteen intensive care units in six countries. PATIENTS: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 +/- 4.8 vs. 9.5 +/- 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01-1.06; p = .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05-1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24-5.16; p = .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06-5.8; p = .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12-3.06; p = .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension. CONCLUSIONS: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor.     

Low caloric intake is associated with nosocomial bloodstream infections in patients in the medical intensive care unit

OBJECTIVE: To determine whether caloric intake is associated with risk of nosocomial bloodstream infection in critically ill medical patients. DESIGN: Prospective cohort study. SETTING: Urban, academic medical intensive care unit. PATIENTS: Patients were 138 adult patients who did not take food by mouth for > or =96 hrs after medical intensive care unit admission. MEASUREMENTS: Daily caloric intake was recorded for each patient. Participants subsequently were grouped into one of four categories of caloric intake: <25%, 25-49%, 50-74%, and > or =75% of average daily recommended calories based on the American College of Chest Physicians guidelines. Simplified Acute Physiology Score II and serum albumin were measured on medical intensive care unit admission. Serum glucose (average value and maximum value each day) and route of feeding (enteral, parenteral, or both) were collected daily. Nosocomial bloodstream infections were identified by infection control surveillance methods. MAIN RESULTS: The overall mean (+/-sd) daily caloric intake for all study participants was 49.4 +/- 29.3% of American College of Chest Physicians guidelines. Nosocomial bloodstream infection occurred in 31 (22.4%) participants. Bivariate Cox analysis revealed that receiving > or =25% of recommended calories compared with <25% was associated with significantly lower risk of bloodstream infection (relative hazard, 0.24; 95% confidence interval, 0.10-0.60). Simplified Acute Physiology Score II also was associated with risk of nosocomial bloodstream infection (relative hazard, 1.27; 95% confidence interval, 1.01-1.60). Average daily serum glucose, admission serum albumin, time to initiating nutritional support, and route of nutrition did not affect risk of bloodstream infection. After adjustment for Simplified Acute Physiology Score II in a multivariable analysis, receiving > or =25% of recommended calories was associated with a significantly lower risk of bloodstream infection (relative hazard, 0.27; 95% confidence interval, 0.11-0.68). CONCLUSIONS: In the context of reducing risk of nosocomial bloodstream infections, failing to provide > or =25% of the recommended calories may be harmful. Higher caloric goals may be necessary to achieve other clinically important outcomes.     

Prognostic significance of different subgroup classifications of critical illness-related corticosteroid insufficiency in patients with septic shock

The purpose of this study was to evaluate the prognostic significance of classification of patients with septic shock into different critical illness-related corticosteroid insufficiency subgroups. A retrospective observational study was conducted in patients with septic shock who underwent a short corticotropin stimulation test within 72 h of the onset of shock. Patients were classified into normal adrenal function (NOM), low basal cortisol (LBC) (basal cortisol, <10 μg/dL), or low Δ cortisol (LDC) (basal cortisol, ≥10 μg/dL; cortisol, <9 μg/dL) groups. A total of 168 septic shock patients were recruited. Forty-two patients (25%) were assigned to the NOM group, 39 (23.2%) to the LBC group, and 87 (51.8%) to the LDC group. All of the patients received hydrocortisone therapy. Patients in the LDC group had significantly higher Simplified Acute Physiology Score 3 (P < 0.001) and Sequential Organ Failure Assessment score (P < 0.001) than did patients in the NOM group. The 28-day mortalities of the NOM, LBC, and LDC groups were 40.5%, 38.5%, and 63.2%, respectively (P = 0.007). Classification into the LDC group significantly increased the odds of 28-day mortality (odds ratio, 2.717; 95% confidence interval, 1.452-5.082; P = 0.002) and remained an independent risk factor for mortality even after controlling for all the other potential risk factors identified (odds ratio, 3.638; 95% confidence interval, 1.418-9.028; P = 0.006). Classification into the LDC group is an independent risk factor for mortality in hydrocortisone-treated septic shock patients.     

Selenium in Intensive Care (SIC): results of a prospective randomized, placebo-controlled, multiple-center study in patients with severe systemic inflammatory response syndrome, sepsis, and septic shock

OBJECTIVE: Sepsis is associated with an increase in reactive oxygen species and low endogenous antioxidative capacity. We postulated that high-dose supplementation of sodium-selenite would improve the outcome of patients with severe sepsis and septic shock. DESIGN: Prospective randomized, placebo-controlled, multiple-center trial. SETTING: Eleven intensive care units in Germany. PATIENTS: Patients were 249 patients with severe systemic inflammatory response syndrome, sepsis, and septic shock and an Acute Physiology and Chronic Health Evaluation (APACHE) III score >70. INTERVENTIONS: Patients received 1000 microg of sodium-selenite as a 30-min bolus injection, followed by 14 daily continuous infusions of 1000 microg intravenously, or placebo. MEASUREMENTS AND MAIN RESULTS: The primary end point was 28-day mortality; secondary end points were survival time and clinical course of APACHE III and logistic organ dysfunction system scores. In addition, selenium levels in serum, whole blood, and urine as well as serum glutathione-peroxidase-3 activity were measured. From 249 patients included, 11 patients had to be excluded. The intention-to-treat analysis of the remaining 238 patients revealed a mortality rate of 50.0% in the placebo group and 39.7% in the selenium-treated group (p = .109; odds ratio, 0.66; confidence interval, 0.39-1.1). A further 49 patients had to be excluded before the final analysis because of severe violations of the study protocol. In the remaining 92 patients of the study group, the 28-day mortality rate was significantly reduced to 42.4% compared with 56.7% in 97 patients of the placebo group (p = .049, odds ratio, 0.56; confidence interval, 0.32-1.00). In predefined subgroup analyses, the mortality rate was significantly reduced in patients with septic shock with disseminated intravascular coagulation (n = 82, p = .018) as well as in the most critically ill patients with an APACHE III score > or =102 (>75% quartile, n = 54, p = .040) or in patients with more than three organ dysfunctions (n = 83, p = .039). Whole blood selenium concentrations and glutathione peroxidase-3 activity were within the upper normal range during selenium treatment, whereas they remained significantly low in the placebo group. There were no side effects observed due to high-dose sodium-selenite treatment. CONCLUSIONS: The adjuvant treatment of patients with high-dose sodium-selenite reduces mortality rate in patients with severe sepsis or septic shock.     

International integrated database for the evaluation of severe sepsis and drotrecogin alfa (activated) therapy: 28-day survival and safety

PURPOSE: To enhance the understanding of severe sepsis, a database of patients from multiple clinical trials spanning a 6-year period was constructed. Initial analyses evaluated the 28-day survival in the placebo group and further assessed the treatment effect of drotrecogin alfa (activated) (DrotAA). METHODS: Five severe sepsis studies with similar entry criteria were combined, and baseline characteristics and 28-day mortality were evaluated (4459 severe sepsis patients; placebo, n = 1231; DrotAA, n = 3228). An integrated data analysis with propensity score adjustment was performed. Twenty-one variables selected by stepwise logistic regression were included in a propensity score of differences between the 2 groups of patients. RESULTS: Over the 6-year period of these trials, there was no change in placebo mortality rates overall (P = .67), nor in subgroups of Acute Physiology and Chronic Health Evaluation score >/=25 (P = .73) or multiple organ dysfunction (P = .38). The adjusted relative hazard risk for DrotAA patients was 0.84 (95% confidence interval, 0.73-0.95; P = .007). Serious bleeding (0.8% in placebo vs 3.5% in DrotAA, P < .0001) was increased during the DrotAA infusion period. CONCLUSIONS: Initial analyses indicate that placebo mortality remained unchanged over a recent 6-year period. These analyses also further substantiate that treatment with DrotAA is associated with improved survival.     

Dopamine therapy in septic shock: Detrimental effect on survival?

Objective

The aim of this study is to examine the potential impact of dopamine therapy on 28-day mortality in adult septic shock.

Methods

For 66 months, clinical data, medications taken before admission, doses of catecholamines used, and biological parameters were recorded prospectively in all patients admitted for septic shock. This observational study was followed by (1) post hoc multivariate analyses and (2) risk-adjusted matched cohort study.

Measurements and main results

In 277 patients (65 ± 14 years; Simplified Acute Physiology Score II = 54 ± 19, 28-day mortality = 45%; hospital mortality = 53%), 6 factors were linked to 28-day mortality, including Simplified Acute Physiology Score II (P < .0001) and the use of dopamine (P = .043). In a pair-matched cohort of 132 patients, we observed a higher mortality with dopamine (28-day mortality of 62% vs 41%, respectively; P = .006). Dopamine remained linked to day 28 mortality by conditional logistic analysis (odds ratio = 6.2 [1.5-25]). A strong interaction between essential hypertension and dopamine was found, associated to 81% 28-day mortality in patients having both conditions.

Conclusions

In our cohort study, dopamine use was linked to mortality as compared to other vasopressor therapies, particularly in patients with essential hypertension. Future randomized studies attempting to compare dopamine with other therapies in septic shock should pay attention to patients with essential hypertension.     

Determinants of postintensive care unit mortality: a prospective multicenter study

OBJECTIVE: Six to 25 percent of patients discharged alive from the intensive care unit (ICU) die before hospital discharge. Although this post-ICU mortality may indicate premature discharge from a full ICU or suboptimal management in the ICU or ward, another factor may be discharge from the ICU as part of a decision to limit treatment of hopelessly ill patients. We investigated determinants of post-ICU mortality, with special attention to this factor. DESIGN: Prospective, multicenter, database study. SETTING: Seven ICUs in or near Paris, France. PATIENTS: A total of 1,385 patients who were discharged alive from an ICU after a stay of > or = 48 hrs; 150 (10.8%) died before hospital discharge. Decisions to withhold or withdraw life-sustaining treatments were implemented in the ICUs in 80 patients, including 47 (58.7%) who died before hospital discharge. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In the univariate analysis, post-ICU mortality was associated with advanced age, poor chronic health status, severe comorbidities, severity and organ failure scores (Simplified Acute Physiology Score II, sepsis-related organ failure assessment, and Logistic Organ Dysfunction at admission and at ICU discharge), decisions to withhold or withdraw life-sustaining treatments, and Omega score (reflecting ICU resource utilization and length of ICU stay). Multivariate stepwise logistic regression identified five independent determinants of post-ICU mortality: McCabe class 1 (odds ratio, 0.388 [95% confidence interval, 0.26-0.58]), transfer from a ward (odds ratio, 1.89 [95% confidence interval, 1.27-2.80]), Simplified Acute Physiology Score II score at admission >36 (odds ratio, 1.57 [95% confidence interval, 1.6-2.33]), decisions to withhold or withdraw life-sustaining treatments (odds ratio, 9.64 [95% confidence interval, 5.75-16.6]), and worse sepsis-related organ failure assessment score at discharge (odds ratio, 1.11 [95% confidence interval, 1.03-1.18] per point). CONCLUSIONS: More than 10% of ICU survivors died before hospital discharge. Determinants of post-ICU mortality included variables reflecting patient status before and during the ICU stay. However, the most powerful predictor of post-ICU mortality was the decision to withhold or withdraw life-sustaining treatments in the ICU, suggesting that the decision has been made not to use the unique services of the ICU for these patients.     

Effect of acute lung injury and acute respiratory distress syndrome on outcome in critically ill trauma patients

OBJECTIVE: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are known to be associated with increased mortality and costs in trauma patients. We estimated the independent impact of these conditions on mortality and cost, beyond the severity of injury with which they are correlated. DESIGN: One-year prospective cohort. PATIENTS AND SETTING: All trauma patients admitted to the intensive care unit in a level I center were evaluated daily for ALI/ARDS using the American-European Consensus Conference definition. MEASUREMENTS AND MAIN RESULTS: The main outcome measures were hospital mortality and costs. Logistic regression was used to model hospital mortality in relation to the presence of ALI and ARDS, adjusting for trauma severity (Injury Severity Score), Acute Physiology Score, and age. Hospital costs were modeled using multivariable linear regression. Of the 1,296 trauma patients surviving beyond the first day, 4% experienced ALI (defined as Pao2/Fio2 of 201-300 mm Hg) and 12% had ARDS (Pao2/Fio2 < or = 200 mm Hg). The crude relative risk of mortality was 2.24 (95% confidence interval, 0.92-5.45) in patients with ALI and 3.84 (95% confidence interval, 2.41-6.13) in patients with ARDS compared with those without ALI/ARDS. However, there was no association of mortality with ALI (relative risk, 0.99; 95% confidence interval, 0.29-3.36) or with ARDS (relative risk, 1.23; 95% confidence interval, 0.63-2.43) after adjustment for age, Injury Severity Score, and Acute Physiology Score. Among patients of comparable age, severity score, and length of stay, median cost was 20% to 30% higher for those with ALI/ARDS. CONCLUSIONS: There is no additional mortality associated with ALI/ARDS above and beyond the factors that can be measured at intensive care unit admission. Therefore, mortality in trauma patients is explained by injury severity at admission and is not affected by the subsequent occurrence of ALI/ARDS. Nonetheless, ALI/ARDS was associated with increased intensive care unit stay and hospital cost, independent of trauma severity.     

Adverse effect on a referral intensive care unit's performance of accepting patients transferred from another intensive care unit

OBJECTIVE: To determine whether observed and predicted mortality for intensive care unit (ICU) transfer admissions is different from non-ICU transfer admissions and how that might affect ICU performance evaluation. DESIGN, SETTING, AND PATIENTS: We retrospectively analyzed the charts of 3,416 patients admitted to our tertiary referral ICU from January 1995 to December 2001 and evaluated the effect on our performance (based on the Simplified Acute Physiology Score II risk model) of accepting patients transferred from another hospital's ICU. MAIN RESULTS: During the study period, 597 patients (17%) had been transferred from a non-ICU setting in another hospital (hospital transfer) and 408 (12%) from another hospital's ICU (ICU transfer). ICU mortality and standardized mortality ratios were significantly higher for ICU-transfer patients than for hospital-transfer or directly admitted patients: 34% vs. 23% vs. 17% (p < .0001) and 0.95 (95% confidence interval, 0.83-1.08), 0.82 (95% confidence interval, 0.71-0.95), and 0.62 (95% confidence interval, 0.55-0.68), respectively. ICU-transfer patients had 3.6-fold longer mean ICU stays and 1.9-fold longer durations of mechanical ventilation than directly admitted patients. Hospital-transfer (odds ratio = 1.89) and ICU-transfer patients (odds ratio = 2.41) had significantly higher mortality rates, even after adjustment for case mix and disease severity. Consequently, a benchmarking program adjusting only for these latter variables, but not admission source, would penalize our ICU by 39 excess deaths per 1,000 admissions as compared with another ICU admitting no transfer patients. Finally, patients transferred from the ward of another hospital had significantly higher mortality rates (odds ratio = 1.56) as compared with patients directly admitted from the ward of our hospital, confirming the "transfer effect" for this homogeneous patients' subgroup. CONCLUSIONS: Admission source remains a strong and independent predictor of ICU death, despite adjustment for case mix and disease severity at ICU admission. Specifically, accepting numerous ICU-transfer patients, for whom the probability of ICU death is the most underestimated by a system adjusting only for case mix and disease severity, can adversely affect the evaluation of referral centers' performance. Future benchmarking and profiling systems should evaluate and adequately account for the ICU-transfer factor to provide healthcare payers and consumers with more accurate and valid information on the true performance of referral centers.     

N-terminal pro-B-type natriuretic peptide is an independent predictor of outcome in an unselected cohort of critically ill patients

OBJECTIVES: Natriuretic peptides emerged during recent years as potent prognostic markers in patients with heart failure and acute myocardial infarction. In addition, natriuretic peptides show strong predictive value in patients with pulmonary embolism, sepsis, renal failure, and shock. The present study tests the prognostic information of N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) in an unselected cohort of critically ill patients. DESIGN: Prospective, observational study. SETTING: A tertiary intensive care unit in a university hospital. PATIENTS: A total of 289 consecutive patients admitted to the intensive care unit during a 16-month period with the following data: age 64 +/- 14 yrs, male n = 191, Simplified Acute Physiology Score II of 52 +/- 24, mechanical ventilation n = 180 (62%), vasopressors n = 179 (62%), renal failure n = 24 (8%). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma NT-pro-BNP samples (Roche Diagnostics) were obtained on intensive care unit admission. Data are given as median [range]. Intensive care unit survivors had significantly lower NT-pro-BNP values compared with intensive care unit nonsurvivors (3394 [24-35,000] vs. 6776 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). Hospital survivors were characterized by significantly lower NT-pro-BNP values (2656 [24-35,000] vs. 8390 [303-35,000] pg/mL, survivors vs. nonsurvivors, respectively, p = .001). NT-pro-BNP levels were not significantly different in patients with primary cardiac diagnosis compared with those with a noncardiac admission diagnosis (4794 [26-35,000], n = 202 vs. 3349 [24-35,000], n = 87, cardiac vs. noncardiac, respectively, p = .28). In a logistic regression model, Simplified Acute Physiology Score II and NT-pro-BNP were independently associated with hospital survival (chi = 35.6, p = .0001 and chi = 11.3, p = .0008, Simplified Acute Physiology Score II and NT-pro-BNP, respectively). Areas under the receiver operating characteristic curves of NT-pro-BNP and Simplified Acute Physiology Score II were not statistically significant different regarding the prediction of outcome. CONCLUSIONS: NT-pro-BNP on admission is an independent prognostic marker of outcome in an unselected cohort of critically ill patients. A single measurement of NT-pro-BNP might facilitate triage of emergency and intensive care unit patients.     

Multicenter study of obstetric admissions to 14 intensive care units in southern England

OBJECTIVES: To identify pregnant and postpartum patients admitted to intensive care units (ICUs), the cause for their admission, and the proportion that might be appropriately managed in a high-dependency environment (HDU) by using an existing database. To estimate the goodness-of-fit for the Simplified Acute Physiology Score II, the Acute Physiology and Chronic Health Evaluation (APACHE) II, and the APACHE III scoring systems in the obstetrical population. DESIGN: Retrospective analysis of demographic, diagnostic, treatment, and severity of illness data. SETTING: Fourteen ICUs in Southern England. PATIENTS: Pregnant or postpartum (<42 days) admissions between January 1, 1994, and December 31, 1996. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 210 patients, constituting 1.84% (210 of 11,385) of all ICU admissions and 0.17% (210 of 122,850) of all deliveries. Most admissions followed postpartum complications (hypertensive disease of pregnancy [39.5%] and major hemorrhage [33.3%]). Seven women were transferred to specialist ICUs. There was considerable variation between ICUs with respect to the number and type of interventions required by patients. Some 35.7% of patients stayed in ICU for <2 days and received no specific ICU interventions; these patients might have been safely managed in an HDU. There were seven maternal deaths (3.3%); fetal mortality rate was 20%. The area under the receiver operator characteristic curve and the standardized mortality ratio were 0.92 (confidence interval [CI], 0.85-0.99) and 0.43 for the Simplified Acute Physiology Score II, 0.94 (CI, 0.86-1.0) and 0.24 for APACHE II, and 0.98 (CI, 0.96-1.0) and 0.43 for APACHE III, respectively. CONCLUSIONS: Existing databases can both identify critically ill obstetrical patients and provide important information about them. Obstetrical ICU admissions often require minimal intervention and are associated with low mortality rates. Many might be more appropriately managed in an HDU. The commonly used severity of illness scoring systems are good discriminators of outcome from intensive care admission in this group but may overestimate mortality rates. Severity of illness scoring systems may require modification in obstetrical patients to adjust for the normal physiologic responses to pregnancy.     

Outcome of patients with end-stage renal disease admitted to the intensive care unit

OBJECTIVES: To describe the clinical course of patients with end-stage renal disease (ESRD) admitted to the intensive care unit (ICU) and to compare the performance of Acute Physiology and Chronic Health Evaluation (APACHE) III and Sequential Organ Failure Assessment (SOFA) in predicting their outcome. PATIENTS AND METHODS: This retrospective cohort study consisted of patients with ESRD admitted to 3 ICUs between January 1, 1997, and November 30, 2002. Data on demographics, APACHE III score, SOFA score, development of sepsis and organ failure, use of mechanical ventilation, and mortality were collected. RESULTS: Of the 476 patients with ESRD who underwent dialysis during the study period, 93 (20%) required admission to the ICU. The most common ICU admission diagnosis was gastrointestinal bleeding. The first day median (Interquartile range) APACHE III score, SOFA score, and APACHE III predicted hospital mortality rate were 64 (47-79), 6 (5-8), and 12.9% (4.2%-30.8%), respectively. The observed ICU, hospital, and 30-day mortality rates were 9%, 16%, and 22%, respectively. Nonrenal organ failure developed in 48 patients (52%) and sepsis in 15 patients (16%). Mechanical ventilation was required In 26 patients (28%). The area under the receiver operating characteristic curve for the first-day APACHE III probability of hospital death in predicting 30-day mortality was 0.78 (95% confidence interval, 0.68-0.86) compared with 0.66 (95% confidence interval, 0.55-0.76) for the SOFA score (P = .16). CONCLUSIONS: The observed hospital mortality of patients with ESRD admitted to the ICU is relatively low. There is no statistically significant difference in the performance of APACHE III and SOFA prognostic models in discriminating between 30-day survivors and nonsurvivors.     

Intensive care in patients with newly diagnosed malignancies and a need for cancer chemotherapy

OBJECTIVE: Patients with newly diagnosed cancer responsible for organ failures may require intensive care unit (ICU) admission and immediate chemotherapy. Outcomes in this population have not been studied. DESIGN: Prospective observational cohort study. SETTING: Teaching hospital. SUBJECTS: All patients admitted to the ICU, from January 1997 to June 2003, for organ failures due to newly diagnosed, untreated cancer and deemed necessary to receive immediate cancer chemotherapy. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the period of 6.5 yrs, 100 patients met the study criteria: 43 had acute leukemia, 37 lymphoma, and 12 solid tumors. Median Simplified Acute Physiology Score II was 39 (30-48) points, and median Logistic Organ Dysfunction score was 5 (3-7) points. Three variables were independently associated with 30-day mortality: need for vasopressor therapy (odds ratio, 6.01; 95% confidence interval, 1.86-19.4), mechanical ventilation (odds ratio, 6.36; 95% confidence interval, 1.76-22.94); and hepatic failure (odds ratio, 7.76; 95% confidence interval, 1.25-48.27). Overall survival was 60% after 30 days and 49% after 180 days. CONCLUSIONS: Mortality was chiefly dependent on the nature and number of organ failures, not on the nature or stage of the malignancy. The 30-day and 180-day survival rates indicate that, in this selected group of patients, advanced disease at cancer diagnosis should not lead to refusal of ICU admission. Moreover, administration of chemotherapy in the intensive care unit is feasible, and although the mortality rate is high, routine ICU admission of patients with newly diagnosed cancer, specific organ failure, and the need for administration of chemotherapy in the ICU deserves evaluation.     

Effectiveness of the rapid emergency medicine score and the rapid acute physiology score in prognosticating mortality in patients presenting to the emergency department with COVID-19 symptoms

ObjectiveWe investigated the effectiveness of the Rapid Emergency Medicine Score and the Rapid Acute Physiology Score in identifying critical patients among those presenting to the emergency department with COVID-19 symptoms.Material and methodsThis prospective, observational, cohort study included patients with COVID-19 symptoms presenting to the emergency department over a two-month period. Demographics, clinical characteristics, and the data of all-cause mortality within 30 days after admission were noted, and the Rapid Emergency Medicine Score and the Rapid Acute Physiology Score were calculated by the researchers. The receiver operating characteristic curve analysis was performed to determine the discriminative ability of the scores.ResultsA total of 555 patients with a mean of age of 49.4 ± 16.8 years were included in the study. The rate of 30-day mortality was 3.9% for the whole study cohort, 7.2% for the patients with a positive rt-PCR test result for SARS-CoV-2, and 1.2% for those with a negative rt-PCR test result for SARS-CoV-2. In the group of patients with COVID-19 symptoms, according to the best Youden's index, the cut-off value for the Rapid Emergency Medicine Score was determined as 3.5 (sensitivity: 81.82%, specificity: 73.08%), and the area under curve (AUC) value was 0.840 (95% confidence interval 0.768–0.913). In the same group, according to the best Youden's index, the cut-off value for the Rapid Acute Physiology Score was 2.5 (sensitivity: 90.9%, specificity: 97.38%), and the AUC value was 0.519 (95% confidence interval 0.393–0.646).ConclusionREMS is able to predict patients with COVID-19-like symptoms without positive rt-PCR for SARS-CoV-2 that are at a high-risk of 30-day mortality. Prospective multicenter cohort studies are needed to provide best scoring system for triage in pandemic clinics.     

Hospital mortality and resource use in subgroups of the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial

OBJECTIVE: To compare differences in hospital mortality and resource use in adult severe sepsis subjects randomized to receive drotrecogin alfa (activated) (DrotAA) or placebo in the PROWESS trial. DESIGN: Retrospective, cross-sectional, blinded follow-up of subjects enrolled in a previous randomized, controlled trial. SETTING: One hundred sixty-four tertiary care institutions in 11 countries. PARTICIPANTS: The 1,690 subjects with severe sepsis enrolled and treated with study drug in PROWESS, of whom 1,220 were alive at 28 days (the end of the original PROWESS follow-up). INTERVENTIONS: DrotAA (n = 850), 24 microg/kg/hr for 96 hrs, or placebo (n = 840). MEASUREMENTS AND MAIN RESULTS: New follow-up data through hospital discharge were merged with existing 28-day follow-up data. Hospital mortality was calculated for designated subgroups. Intensive care unit and hospital length of stay and Simplified Therapeutic Intervention Scoring System-28 (TISS-28) scores were calculated overall and in designated subgroups. Hospital discharge location was recorded. The 95% confidence interval of most subgroups contained the relative risk estimate for overall 28-day and hospital mortality. Median hospital length of stay and intensive care unit length of stay were similar in both treatment groups: 16 vs. 17 days (p = .22) and 9 vs. 9 days (p = .7) for placebo vs. DrotAA. No significant difference in TISS-28 scores was observed between treatment groups overall or in subgroups of disease severity. In subjects for whom discharge destination was reported, 42.8% of placebo subjects and 46.8% of DrotAA subjects (two thirds of survivors in each group) were discharged directly to home. CONCLUSIONS: Reduction in hospital mortality with DrotAA in most of the subgroups of PROWESS is consistent with the reduction in 28-day and hospital mortality observed in the overall PROWESS population. Additional survivors created with DrotAA treatment did not increase per-patient resource use or intensive care unit or hospital length of stay.     

Complicated acute myocardial infarction requiring mechanical ventilation in the intensive care unit: prognostic factors of clinical outcome in a series of 157 patients

OBJECTIVE: To determine prognostic factors associated with death in patients with complicated acute myocardial infarction requiring mechanical ventilation. DESIGN: Retrospective chart-based analysis. SETTING: A 22-bed medical intensive care unit in a university hospital. PATIENTS: A total of 157 consecutive patients with acute myocardial infarction requiring endotracheal intubation and mechanical ventilation admitted to an intensive care unit during a 6-yr period. INTERVENTIONS: Coronary reperfusion strategy within 12 hrs following symptom onset. MEASUREMENTS AND MAIN RESULTS: Clinical characteristics at admission of survivors (n = 77) and nonsurvivors (n = 80) were similar regarding demographics, medical history, and Glasgow Coma Scale score. Twenty-eight-day intensive care unit mortality rate was 51%. The following criteria were higher for nonsurvivors: Simplified Acute Severity Score II, 79 +/- 18 vs. 64 +/- 17 (p <.0001); Acute Physiology and Chronic Health Evaluation (APACHE) II, 33 +/- 13 vs. 25 +/- 6 (p <.0001); incidence of cardiogenic shock (p =.0085) and failing organs (p <.0001); coronary artery disease extension (p =.045); and delay between symptom onset and coronary reperfusion (p =.0348). Nonsurvivors also had higher serum urea and creatinine and lower urine output, arterial pH, and left ventricular ejection fraction (p <.05). Mortality rate was higher in patients with PaO2/FiO2 ratio <200 than in patients with PaO2/FiO2 ratio >200 at admission (log-rank, 5.016; p =.0251). By multivariate analysis, only three factors were independently associated with death: APACHE II >29 (odds ratio, 1.132; 95% confidence interval, 1.013-1.265, p =.0287), serum creatinine >180 micromol/L (odds ratio, 6.151; 95% confidence interval, 1.446-26.166, p =.0139), and initial left ventricular ejection fraction <0.4 (odds ratio, 1.121; 95% confidence interval, 1.049-1.347, p =.0316). Overall, good discrimination was achieved for the risk score model (c-index, 0.852). CONCLUSIONS: We confirmed the high mortality rate of patients admitted to an intensive care unit with acute myocardial infarction requiring mechanical ventilation. In these patients, the main risk factors for death found, namely high APACHE II, early development of acute renal failure, and low resting left ventricular function, reflected the severity of the myocardial infarction.     

Thrombocytopenia and prognosis in intensive care

OBJECTIVE: To study the incidence and prognosis of thrombocytopenia in adult intensive care unit (ICU) patients. DESIGN: Prospective observational cohort study. SETTING: The medical ICU of a university hospital and the combined medical-surgical ICU of a regional hospital. PATIENTS: All patients consecutively admitted during a 5-month period. INTERVENTIONS: Patient surveillance and data collection. MEASUREMENTS AND MAIN RESULTS: The primary outcome measure was ICU mortality. Data of 329 patients were analyzed. Overall ICU mortality rate was 19.5%. A total of 136 patients (41.3%) had at least one platelet count <150 x 10(9)/L. These patients had higher Multiple Organ Dysfunction Score (MODS), Simplified Acute Physiology Score (SAPS) II, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores at admission, longer ICU stay (8 [4-16] days vs. 5 [2-9] days) (median [interquartile range]), and higher ICU mortality (crude odds ratio [OR], 5.0; 95% confidence interval [CI], 2.7-9.1) and hospital mortality than patients with daily platelet counts >150 x 10(9)/L (p < .0005 for all comparisons). Bleeding incidence rose from 4.1% in nonthrombocytopenic patients to 21.4% in patients with minimal platelet counts between 101 x 10(9)/L and 149 x 10(9)/L (p = .0002) and to 52.6% in patients with minimal platelet counts <100 x 10(9)/L (p < .0001). In all quartiles of admission APACHE II and SAPS II scores, a nadir platelet count <150 x 10(9)/L was related with a substantially poorer vital prognosis. Similarly, a drop in platelet count to < or =50% of admission was associated with higher death rates (OR, 6.0; 95% CI, 3.0-12.0; p < .0001). In a logistic regression analysis with ICU mortality as the dependent variable, the occurrence of thrombocytopenia had more explanatory power than admission variables, including APACHE II, SAPS II, and MODS scores (adjusted OR, 4.2; 95% CI, 1.8-10.2). CONCLUSIONS: Thrombocytopenia is common in ICUs and constitutes a simple and readily available risk marker for mortality, independent of and complementary to established severity of disease indices. Both a low nadir platelet count and a large fall of platelet count predict a poor vital outcome in adult ICU patients.     

Candida as a risk factor for mortality in peritonitis

OBJECTIVE: The clinical significance of Candida cultured from peritoneal fluid specimens remains a matter of debate. None of the studies that have addressed this issue have clearly distinguished between community-acquired peritonitis and nosocomial peritonitis. The current study tried to differentiate the pathogenic role of Candida in these two clinical settings and assess its importance on outcome. DESIGN: A multiple-center, retrospective, case-control study was conducted in intensive care unit patients. The interaction between mortality rates and type of patients was assessed. In the case of a significant interaction, a separate analysis of mortality and morbidity was planned. SETTING: Seventeen intensive care units in teaching and nonteaching hospitals. PATIENTS: Cases were patients operated on for peritonitis with Candida cultured from the peritoneal fluid, whereas controls were operated patients free from yeast. Cases and controls were matched for type of infection, Simplified Acute Physiology Score II, age, and time period of hospitalization. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The following characteristics were collected: demographic variables, underlying disease, severity score, site of infection, microbiological features, and anti-infective treatments. Survival was defined as the main outcome criterion and morbidity variables as secondary criteria. Odds ratios of mortality were calculated. Matching was achieved in 91 cases and 168 controls. Matching criteria, clinical characteristics, and mortality rate were not statistically different between cases and controls. A significant interaction was demonstrated between mortality rates and type of infection, leading to separate analysis of patients with community-acquired peritonitis and nosocomial peritonitis. The subgroup analysis demonstrated an increased mortality rate only in nosocomial peritonitis with fungal isolates (48% vs. 28% in controls, p<.01). Upper gastrointestinal tract site (odds ratio, 4.9; 95% confidence interval, 1.6-14.8) and isolation of Candida species (odds ratio, 3.0; 95% confidence interval, 1.3-6.7, p<.001) were found to be independent risk factors of mortality in nosocomial peritonitis patients. CONCLUSIONS: Isolation of Candida species appears to be an independent risk factor of mortality in nosocomial peritonitis but not in community-acquired peritonitis.