Risk Factors for Loss of Lung Sliding in a Medical Intensive Care Population With Acute Respiratory Failure.

BACKGROUND: Point of care bedside ultrasound is widely utilized as a rapid technique to evaluate patients with acute pulmonary emergencies, including acute pneumothorax. The presence of a pneumothorax is a known cause of loss of lung sliding by ultrasound examination, but no other risk factors have been clearly identified. We attempted to identify demographic and patient characteristics that are risk factors for loss of ultrasonographic lung sliding in the absence of a pneumothorax. METHODS: Data were collected on 159 patients admitted to the medical intensive care unit with acute respiratory failure, undergoing routine admission lung ultrasound. The lung ultrasound examination consisted of 3 views of each hemithorax using a phased array abdominal probe. RESULTS: There were 4 confirmed pneumothoraces out of 20 patients with loss of lung sliding at ≥1 ultrasound interrogation points on either hemithorax. Hypercarbic respiratory failure [odds ratio (OR), 5.59] and low body mass index (OR, 0.88) were statistically significant risk factors for the loss of lung sliding in the absence of pneumothorax. There was a trend toward significance in patients with a known history of a decreased forced expiratory volume 1/forced vital capacity ratio (OR, 0.02), COPD/asthma exacerbation as the cause of their respiratory failure (OR, 4.52) and previous pneumothorax (OR, 11.53). CONCLUSION: Common diagnoses and comorbidities are associated with the loss of ultrasonographic lung sliding, in the absence of pneumothorax.

Discrepancies in measuring bladder volumes with bedside ultrasound and bladder scanning in the intensive care unit: A pilot study.

OBJECTIVE: Intensive care unit patients are at risk for catheter-associated urinary tract infection. Earlier removal of catheters may be possible with accurate measurement of bladder volume. The purpose was to compare measured bladder volumes with bedside ultrasound, bladder scanner, and urine volume. DESIGN: Prospective correlational descriptive study. SETTING: Surgical/trauma intensive care unit and medical intensive care unit. PATIENTS: Renal dialysis patients with less than 100 ml of urine in 24 h prior to urinary catheter removal and patients with suspected catheter obstruction. MEASUREMENTS AND MAIN RESULTS: A physician trained in ultrasound and an advanced practice registered nurse trained in bladder scanning measured bladder volume; each blinded to the other's measurement. Device used first (ultrasound or bladder scanner) alternated daily. The intensive care unit team determined need for intermittent catheterization or treatment for suspected obstruction. Fifty-one measurements from 13 patients were obtained with results reported in milliliters. Ultrasound measurements were a mean volume of 72.1 ± 127 (range: 1.7-666) and the bladder scanner measurements were 117 ± 131 (0-529). On six occasions in five dialysis patients, urine volume measurement was available. The mean difference in ultrasound-urine volume mean difference was 0.5 ± 37.8 (range: -68 to 38.2) and the bladder scanner-urine volume was 132 ± 167 (-72 to 397). Two patients with suspected catheter obstructions had ultrasound, bladder scanner, urine volume measurements, respectively: (1) 539, 51, >300 (began voiding before catheter replaced); (2) 666, 68, 1000 with catheter replacement. Conditions leading to greatest differences were obesity, indwelling catheter and ascites. CONCLUSIONS: These results demonstrate the inaccuracy of the bladder scanner. Ultrasound measurements appear more accurate. To remove urinary catheters in patients with minimal to low urine output, serial ultrasound measurements can be used to monitor bladder volumes and return of renal function.

Rituximab Induced Pulmonary Edema Managed with Extracorporeal Life Support.

Though rare, rituximab has been reported to induce severe pulmonary edema. We describe the first report of ECLS utilization for this indication. A 31-year-old female with severe thrombotic thrombocytopenic purpura developed florid pulmonary edema after rituximab infusion. Despite advanced ventilatory settings, she developed severe respiratory acidosis and remained hypoxemic with a significant vasopressor requirement. Since her pulmonary insult was likely transient, ECLS was considered. Due to combined cardiorespiratory failure, she received support with peripheral venoarterial ECLS. During her ECLS course, she received daily plasmapheresis and high dose steroids. Her pulmonary function recovered and she was decannulated after 8 days. She was discharged after 23 days without residual sequelae.

The peroxisome proliferator-activated receptor agonist pioglitazone and 5-lipoxygenase inhibitor zileuton have no effect on lung inflammation in healthy volunteers by positron emission tomography in a single-blind placebo-controlled cohort study.

BACKGROUND: Anti-inflammatory drug development efforts for lung disease have been hampered in part by the lack of noninvasive inflammation biomarkers and the limited ability of animal models to predict efficacy in humans. We used 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) in a human model of lung inflammation to assess whether pioglitazone, a peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist, and zileuton, a 5-lipoxygenase inhibitor, reduce lung inflammation. METHODS: For this single center, single-blind, placebo-controlled cohort study, we enrolled healthy volunteers sequentially into the following treatment cohorts (N = 6 per cohort): pioglitazone plus placebo, zileuton plus placebo, or dual placebo prior to bronchoscopic endotoxin instillation. 18F-FDG uptake pre- and post-endotoxin was quantified as the Patlak graphical analysis-determined Ki (primary outcome measure). Secondary outcome measures included the mean standard uptake value (SUVmean), post-endotoxin bronchoalveolar lavage (BAL) cell counts and differentials and blood adiponectin and urinary leukotriene E4 (LTE4) levels, determined by enzyme-linked immunosorbent assay, to verify treatment compliance. One- or two-way analysis of variance assessed for differences among cohorts in the outcome measures (expressed as mean ± standard deviation). RESULTS: Ten females and eight males (29±6 years of age) completed all study procedures except for one volunteer who did not complete the post-endotoxin BAL. Ki and SUVmean increased in all cohorts after endotoxin instillation (Ki increased by 0.0021±0.0019, 0.0023±0.0017, and 0.0024±0.0020 and SUVmean by 0.47±0.14, 0.55±0.15, and 0.54±0.38 in placebo, pioglitazone, and zileuton cohorts, respectively, p<0.001) with no differences among treatment cohorts (p = 0.933). Adiponectin levels increased as expected with pioglitazone treatment but not urinary LTE4 levels as expected with zileuton treatment. BAL cell counts (p = 0.442) and neutrophil percentage (p = 0.773) were similar among the treatment cohorts. CONCLUSIONS: Endotoxin-induced lung inflammation in humans is not responsive to pioglitazone or zileuton, highlighting the challenge in translating anti-inflammatory drug efficacy results from murine models to humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT01174056.

Performance of a Modern Glucose Meter in ICU and General Hospital Inpatients: 3 Years of Real-World Paired Meter and Central Laboratory Results.

OBJECTIVE: Due to accuracy concerns, the Food and Drug Administration issued guidances to manufacturers that resulted in Center for Medicare and Medicaid Services stating that the use of meters in critically ill patients is "off-label" and constitutes "high complexity" testing. This is causing significant workflow problems in ICUs nationally. We wished to determine whether real-world accuracy of modern glucose meters is worse in ICU patients compared with non-ICU inpatients. DESIGN: We reviewed glucose results over the preceding 3 years, comparing results from paired glucose meter and central laboratory tests performed within 60 minutes of each other in ICU versus non-ICU settings. SETTING: Seven ICU and 30 non-ICU wards at a 1,300-bed academic hospital in the United States. SUBJECTS: A total of 14,763 general medicine/surgery inpatients and 20,970 ICU inpatients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Compared meter results with near simultaneously performed laboratory results from the same patient by applying the 2016 U.S. Food and Drug Administration accuracy criteria, determining mean absolute relative difference and examining where paired results fell within the Parkes consensus error grid zones. A higher percentage of glucose meter results from ICUs than from non-ICUs passed 2016 Food and Drug Administration accuracy criteria (p < 10) when comparing meter results with laboratory results. At 1 minute, no meter result from ICUs posed dangerous or significant risk by error grid analysis, whereas at 10 minutes, less than 0.1% of ICU meter results did, which was not statistically different from non-ICU results. CONCLUSIONS: Real-world accuracy of modern glucose meters is at least as accurate in the ICU setting as in the non-ICU setting at our institution.

Obliterative Bronchiolitis.

Obliterative bronchiolitis (OB) is a clinical syndrome marked by progressive dyspnea and cough with the absence of parenchymal lung disease on radiographic studies. Pulmonary function testing reveals an obstructive ventilatory defect that is typically not reversed by inhaled bronchodilator. Transbronchial biopsies are insufficiently sensitive to achieve diagnosis, and in most cases, clinical, physiological, and radiological data obviate the need for the increased risk associated with open lung biopsy. This diagnosis has been documented in a variety of exposures, including fumes from flavoring plants, smoke from burn pits, and environmental sulfur gas. Among lung transplant recipients, "bronchiolitis obliterans syndrome," a disorder with clinical and histopathological similarity to OB, represents the leading cause of long-term allograft dysfunction and mortality. After hematopoietic stem cell transplantation, chronic graft versus host disease of the lung manifests most frequently with similar clinical and pathological features. In all circumstances, immunologic and nonimmunologic mechanisms are thought to lead to airway epithelial dysfunction, which results in progressive airflow obstruction and debility. Augmentation of immunosuppression is occasionally effective in slowing or reversing the progression of disease though a significant number of patients will be nonresponders. Other immunomodulatory methods have been attempted in each circumstance where this pathology has been identified. Unfortunately, OB is poorly understood and often results in sufficient progression of disease to warrant evaluation for lung transplantation (or retransplantation). Here, we review what is known regarding pathophysiology and discuss clinical, pathological, radiological, and therapeutic factors associated with the spectrum of OB-related disease with a particular focus on lung transplantation.

Imaging pulmonary inducible nitric oxide synthase expression with PET.

UNLABELLED: Inducible nitric oxide synthase (iNOS) activity increases in acute and chronic inflammatory lung diseases. Imaging iNOS expression may be useful as an inflammation biomarker for monitoring lung disease activity. We developed a novel tracer for PET that binds to iNOS in vivo, (18)F-NOS. In this study, we tested whether (18)F-NOS could quantify iNOS expression from endotoxin-induced lung inflammation in healthy volunteers. METHODS: Healthy volunteers were screened to exclude cardiopulmonary disease. Qualifying volunteers underwent a baseline, 1-h dynamic (18)F-NOS PET/CT scan. Endotoxin (4 ng/kg) was then instilled bronchoscopically in the right middle lobe. (18)F-NOS imaging was performed again approximately 16 h after endotoxin instillation. Radiolabeled metabolites were determined from blood samples. Cells recovered by bronchoalveolar lavage (BAL) after imaging were stained immunohistochemically for iNOS. (18)F-NOS uptake was quantified as the distribution volume ratio (DVR) determined by Logan plot graphical analysis in volumes of interest placed over the area of endotoxin instillation and in an equivalent lung region on the left. The mean Hounsfield units (HUs) were also computed using the same volumes of interest to measure density changes. RESULTS: Seven healthy volunteers with normal pulmonary function completed the study with evaluable data. The DVR increased by approximately 30%, from a baseline mean of 0.42 ± 0.07 to 0.54 ± 0.12, and the mean HUs by 11% after endotoxin in 6 volunteers who had positive iNOS staining in BAL cells. The DVR did not change in the left lung after endotoxin. In 1 volunteer with low-level iNOS staining in BAL cells, the mean HUs increased by 7% without an increase in DVR. Metabolism was rapid, with approximately 50% of the parent compound at 5 min and 17% at 60 min after injection. CONCLUSION: (18)F-NOS can be used to image iNOS activity in acute lung inflammation in humans and may be a useful PET tracer for imaging iNOS expression in inflammatory lung disease.

Non-invasive stroke volume measurement and passive leg raising predict volume responsiveness in medical ICU patients: an observational cohort study.

INTRODUCTION: The assessment of volume responsiveness and the decision to administer a fluid bolus is a common dilemma facing physicians caring for critically ill patients. Static markers of cardiac preload are poor predictors of volume responsiveness, and dynamic markers are often limited by the presence of spontaneous respirations or cardiac arrhythmias. Passive leg raising (PLR) represents an endogenous volume challenge that can be used to predict fluid responsiveness. METHODS: Medical intensive care unit (ICU) patients requiring volume expansion were eligible for enrollment. Non-invasive measurements of stroke volume (SV) were obtained before and during PLR using a transthoracic Doppler ultrasound device prior to volume expansion. Measurements were then repeated following volume challenge to classify patients as either volume responders or non-responders based on their hemodynamic response to volume expansion. The change in SV from baseline during PLR was then compared with the change in SV with volume expansion to determine the ability of PLR in conjunction with SV measurement to predict volume responsiveness. RESULTS: A total of 102 fluid challenges in 89 patients were evaluated. In 47 of the 102 fluid challenges (46.1%), SV increased by > or =15% after volume infusion (responders). A SV increase induced by PLR of > or =15% predicted volume responsiveness with a sensitivity of 81%, specificity of 93%, positive predictive value of 91% and negative predictive value of 85%. CONCLUSIONS: Non-invasive SV measurement and PLR can predict fluid responsiveness in a broad population of medical ICU patients. Less than 50% of ICU patients given fluid boluses were volume responsive.

[18F]fluorodeoxyglucose positron emission tomography for lung antiinflammatory response evaluation.

RATIONALE: Few noninvasive biomarkers for pulmonary inflammation are currently available that can assess the lung-specific response to antiinflammatory treatments. Positron emission tomography with [(18)F]fluorodeoxyglucose (FDG-PET) is a promising new method that can be used to quantify pulmonary neutrophilic inflammation. OBJECTIVES: To evaluate the ability of FDG-PET to measure the pulmonary antiinflammatory effects of hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and recombinant human activated protein C (rhAPC) in a human model of experimentally-induced lung inflammation. METHODS: Eighteen healthy volunteers were randomized to receive placebo, lovastatin, or rhAPC before intrabronchial segmental endotoxin challenge. FDG-PET imaging was performed before and after endotoxin instillation. The rate of [(18)F]FDG uptake was calculated as the influx constant K(i) by Patlak graphical analysis. Bronchoalveolar lavage (BAL) was performed to determine leukocyte concentrations for correlation with the PET imaging results. MEASUREMENTS AND MAIN RESULTS: There was a statistically significant decrease in K(i) in the lovastatin-treated group that was not seen in the placebo-treated group, suggesting attenuation of inflammation by lovastatin treatment despite a small decrease in BAL total leukocyte and neutrophil counts that was not statistically significant. No significant decrease in K(i) was observed in the rhAPC-treated group, correlating with a lack of change in BAL parameters and indicating no significant antiinflammatory effect with rhAPC. CONCLUSIONS: FDG-PET imaging is a sensitive method for quantifying the lung-specific response to antiinflammatory therapies and may serve as an attractive platform for assessing the efficacy of novel antiinflammatory therapies at early phases in the drug development process. Clinical trial registered with www.clinicaltrials.gov (NCT00741013).

Probiotics for the prevention of nosocomial pneumonia: current evidence and opinions.

PURPOSE OF REVIEW: Nosocomial infections are common and are associated with considerable morbidity and mortality. The continuing evolution of multidrug resistant pathogens and ineffective therapy for the infections they cause has stimulated interest in the potential of probiotic products to prevent nosocomial infections. Probiotics are viable microorganisms that colonize the host and exert antibacterial and immunomodulatory effects. This article will review the current evidence for probiotics in preventing nosocomial infections, particularly pneumonia in a diverse population of critically ill patients. RECENT FINDINGS: Currently, there are insufficient data to conclusively determine whether probiotics are beneficial in the prevention of nosocomial infections, particularly nosocomial pneumonia. Most of the current literature is limited by poor trial design, inadequate blinding, small study samples, and poorly defined endpoints. SUMMARY: Probiotic products reduce pathogenic colonization of the host. Despite the theoretical plausibility, there is currently insufficient evidence that probiotic products reduce the incidence of nosocomial pneumonia. Large, multicenter, randomized clinical trials utilizing a rigorous, invasive diagnostic approach to nosocomial pneumonia need to be performed to prospectively evaluate the utility of probiotic products. In addition, bench research needs to be performed to select the most appropriate probiotic formulation for different clinical applications.

A retrospective analysis of possible renal toxicity associated with vancomycin in patients with health care-associated methicillin-resistant Staphylococcus aureus pneumonia.

OBJECTIVE: The goal of this investigation was to determine whether more aggressive vancomycin dosing is associated with greater risk for renal toxicity in patients with health care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA). METHODS: This was a retrospective, single-center, observational cohort study. The following information was obtained for all study patients from automated hospital, microbiology, and pharmacy databases: age, sex, weight, serial serum creatinine (SCr), age- and sex-adjusted creatinine clearance (CrCl) during receipt of vancomycin, vancomycin serum trough concentrations, duration of vancomycin therapy, and Acute Physiology and Chronic Health Evaluation II scores. Renal toxicity was defined as either a 0.5-mg/dL increase from baseline in SCr or a >or=50% increase in SCr based on serial SCr measurements. Data for patients who met the definition of renal toxicity were compared with data for those who did not. RESULTS: Ninety-four patients (mean [SD]age, 59.0 [15.6] years; 59 [62.8%] men; 73 (77.7%) white; mean baseline CrCl, 70.3 [23.0] mL/min) were identified as having MRSA HCAP. Forty (42.6%) patients developed renal toxicity. Patients who developed renal toxicity were significantly more likely than patients who did not develop renal toxicity to have greater mean vancomycin serum trough concentrations (20.8 [9.9] g/mL vs 14.3 [6.7] g/mL, respectively; P < 0.001), vancomycin serum trough concentrations >or=15 g/mL (67.5% vs 40.7%; P = 0.01), and a prolonged duration (>or=14 days) of vancomycin treatment (45.0% vs 20.4%; P = 0.011). Logistic regression analysis identified a maximum vancomycin serum trough concentration of >or=15 g/mL as being independently associated with renal toxicity (adjusted odds ratio = 2.82; 95% CI, 1.02-7.74; P = 0.045). The overall mean change in CrCl for the study population was -13.5 (-16.0) mL/min (range, 0.0 to -62.6 mL/min). Patients with maximum measured vancomycin serum trough concentrations >or=15 g/mL (n = 49) had significantly greater absolute changes in CrCl compared with patients with maximum measured vancomycin serum trough concentrations <15 g/mL (n = 45) (-18.9 [-17.0] vs -7.6 [-12.5] mL/min, respectively; P < 0.001). CONCLUSIONS: The results suggest that aggressive vancomycin dosing and prolonged vancomycin administration may be associated with greater risk for renal toxicity in patients with MRSA HCAP. However, this retrospective study cannot establish causation, and a prospective, randomized, double-blind trial is needed.

Probiotics for preventing and treating nosocomial infections: review of current evidence and recommendations.

OBJECTIVE: To review the available clinical data supporting the use of probiotics in preventing and treating serious nosocomial infections. DATA SOURCE: A Medline database from 1996 to July 2006 and references from identified articles were used to perform a literature search relating to the clinical applications of probiotics in preventing and treating Clostridium difficile-associated diarrhea (CDD) and prevention of hospital-associated pneumonia (HAP). CONCLUSION: Nosocomial infections like HAP and CDD contribute significantly to health-care costs in the United States. These clinical problems are associated with prolonged hospital stays and increased mortality in critically ill patients. The emergence of multidrug-resistant pathogens in cases of HAP and the recent description of an epidemic, toxin gene-variant strain of C difficile, combined with the anticipated lack of new antimicrobial agents in the near future emphasize the need for new, innovative strategies to prevent and treat these diseases. Probiotics normally function as colonizers and contribute to the overall health of their hosts by multiple mechanisms including immune and antibacterial effects. There is no current clinical evidence to support the use of probiotics to restore the normal human flora in critically ill patients and reduce HAP rates. Probiotics can prevent episodes of antibiotic-associated diarrhea, but their utility in treating and preventing CDD requires demonstration of benefit in multicenter clinical trials, preferably sponsored by the National Institutes of Health.

Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices.

OBJECTIVE: The goal of this investigation was to determine whether vancomycin pharmacokinetic indexes (eg, serum trough concentrations or area under the concentration curve [AUC] values) were associated with mortality for patients with health-care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching facility. PATIENTS: Adult patients requiring hospitalization who were identified as having HCAP attributed to MRSA by BAL semi-quantitative cultures. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: One hundred two patients with MRSA HCAP were identified over a 6.5-year period. Thirty-two patients (31.4%) died during their hospitalization. The mean (+/- SD) vancomycin trough concentrations (13.6 +/- 5.9 vs 13.9 +/- 6.7 microg/mL, respectively; p = 0.866) and AUC values (351 +/- 143 vs 354 +/- 109 microg/h/mL, respectively; p = 0.941) did not differ between survivors and nonsurvivors. The stratification of the vancomycin trough concentrations and AUC values yielded no relationship with hospital mortality. CONCLUSIONS: We found no evidence that greater vancomycin trough concentrations or AUC values correlated with hospital outcome. Based on these results, aggressive dosing strategies for vancomycin (eg, trough concentrations of > 15 microg/mL) may not offer any advantage over traditional dose targets (range, 5 to 15 microg/mL).

Extravascular lung water measurements and hemodynamic monitoring in the critically ill: bedside alternatives to the pulmonary artery catheter.

The recently completed Fluid and Catheter Treatment Trial conducted by the National Institutes of Health ARDSNetwork casts doubt on the value of routine pulmonary artery catheterization for hemodynamic management of the critically ill. Several alternatives are available, and, in this review, we evaluate the theoretical, validation, and empirical databases for two of these: transpulmonary thermodilution measurements (yielding estimates of cardiac output, intrathoracic blood volume, and extravascular lung water) that do not require a pulmonary artery catheter, and hemodynamic measurements (including estimates of cardiac output and ejection time, a variable sensitive to intravascular volume) obtained by esophageal Doppler analysis of blood flow through the descending aorta. We conclude that both deserve serious consideration as a means of acquiring useful hemodynamic data for managing shock and fluid resuscitation in the critically ill, especially in those with acute lung injury and pulmonary edema, but that additional study, including carefully performed, prospective clinical trials demonstrating outcome benefit, is needed.

Preventing ventilator-associated pneumonia: an evidence-based approach of modifiable risk factors.

There is considerable evidence to suggest that specific interventions can be effectively employed to prevent hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP). These interventions consist of pharmacological and nonpharmacological strategies that focus on prevention of aerodigestive tract colonization and the prevention of aspiration of contaminated secretions, the major pathogenetic mechanisms leading to HAP. Important components of effective preventive strategies focus on basic infection control principles like handwashing, adequate intensive care unit (ICU) staff education, and optimal resource utilization. Measures to prevent HAP/VAP extend into all aspects of daily intensive care practice, including antibiotic selection and duration of use, preferred routes of intubation, limitation of sedation, protocolized weaning, optimal use of noninvasive mask ventilation, patient positioning, ventilator circuit management, transfusion practices, nutritional support issues, stress ulcer prophylaxis, and glycemic control. Local programs encompassing these interventions should be applied at a multidisciplinary level, involve all caregivers, and include local surveillance programs for antibiotic-resistant bacteria. The importance of implementing preventive strategies is amplified by the anticipated limited availability of new antimicrobial drug classes for the foreseeable future. Effective implementation of these preventive principles can result in significant cost savings for society and reduce hospital mortality and morbidity for individual patients.

Predictors of hospital mortality for patients with severe sepsis treated with Drotrecogin alfa (activated).

STUDY OBJECTIVE: To identify predictors of hospital mortality among patients with severe sepsis who were treated with drotrecogin alfa (activated). DESIGN: Prospective observational cohort study. SETTING: A 1400-bed academic medical center. PATIENTS: One hundred two patients treated with drotrecogin alfa (activated) for severe sepsis. MEASUREMENTS AND MAIN RESULTS: To identify potential risk factors for hospital mortality, the main outcome evaluated, all patients who received drotrecogin alfa (activated) were segregated according to hospital survival. The following characteristics were recorded: age, sex, weight, surgical or nonsurgical, Acute Physiology and Chronic Health Evaluation (APACHE) II score, number of acquired organ-system derangements, mechanical ventilation, use of vasopressors or dobutamine, patient location 24 hours before receiving drotrecogin alfa (activated), source of infection, microbiologically positive culture, and other process-of-care variables. Of the 102 patients, 43 (42.2%) died during their hospitalization. Potential predictors of hospital mortality identified by univariate analysis included greater APACHE II scores, administration of vasopressin or dobutamine, number of acquired organ-system derangements, time to treatment with drotrecogin alfa (activated), intravenous fluid administered before receiving vasopressors or drotrecogin alfa (activated), number of red blood cell transfusions, and administration of inappropriate initial antimicrobial treatment. Multivariate analysis revealed that vasopressin administration (odds ratio [OR] 3.72, 95% confidence interval [CI] 1.95-7.10), number of acquired organ-system derangements (OR 2.30, 95% CI 1.59-3.31), and administration of inappropriate initial antimicrobial treatment (OR 15.5, 95% CI 6.78-35.6) were independently associated with hospital mortality. CONCLUSION: Number of acquired organ-system derangements, vasopressin administration, and treatment with an inappropriate initial antimicrobial regimen are independently associated with an increased risk of hospital mortality among patients treated with drotrecogin alfa (activated) for severe sepsis. These findings suggest that other specific medical interventions may increase survival in this patient population.