Rationale: Microvascular injury, inflammation, and coagulation play critical roles in the pathogenesis of acute lung injury (ALI). Plasma protein C levels are decreased in patients with acute lung injury and are associated with higher mortality and fewer ventilator-free days. Objectives: To test the efficacy of activated protein C (APC) as a therapy for patients with ALI. Methods: Eligible subjects were critically ill patients who met the American/European consensus criteria for ALI. Patients with severe sepsis and an APACHE II score of 25 or more were excluded. Participants were randomized to receive APC (24 mg/kg/h for 96 h) or placebo in a double-blind fashion within 72 hours of the onset of ALI. The primary endpoint was ventilator-free days. Measurements and Main Results: APC increased plasma protein C levels (P 5 0.002) and decreased pulmonary dead space fraction (P 5 0.02). However, there was no statistically significant difference between patients receiving placebo (n 5 38) or APC (n 5 37) in the number of ventilator-free days (median [25-75% interquartile range]: 19 [0-24] vs. 19 [14-22], respectively; P 5 0.78) or in 60-day mortality (5/38 vs. 5/37 patients, respectively; P 5 1.0). There were no differences in the number of bleeding events between the two groups. Conclusions: APC did not improve outcomes from ALI. The results of this trial do not support a large clinical trial of APC for ALI in the absence of severe sepsis and high disease severity. Clinical trial registered with www.clinicaltrials.gov (NCT 00112164).

Objective To summarize the current literature on racial and gender disparities in critical care and the mechanisms underlying these disparities in the course of acute critical illness. Data Sources MEDLINE search on the published literature addressing racial, ethnic, or gender disparities in acute critical illness such as sepsis, acute lung injury, pneumonia, venous thromboembolism, and cardiac arrest. Study Selection Clinical studies that evaluated general critically ill patient populations in the United States as well as specific critical care conditions were reviewed with a focus on studies evaluating factors and contributors to health disparities. Data Extraction Study findings are presented according to their association with the incidence, clinical presentation, management, and outcomes in acute critical illness. Data Synthesis This review presents potential contributors for racial and gender disparities related to genetic susceptibility, comorbidities, preventive health services, socioeconomic factors, cultural differences, and access to care. The data is organized along the course of acute critical illness. Conclusions The literature to date shows that disparities in critical care are most likely multifactorial involving individual, community, and hospital-level factors at several points in the continuum of acute critical illness. The data presented identify potential targets as interventions to reduce disparities in critical care and future avenues for research.

Objectives Obesity is increasingly encountered in the intensive care units (ICUs) but the relationship between obesity and acute kidney injury (AKI) is unclear. We aim to evaluate whether body mass index (BMI) was associated with AKI in the acute respiratory distress syndrome (ARDS) and to examine the association between AKI and mortality in patients with and without obesity. Design, Setting, Patients Retrospective study of a cohort of 751 patients with ARDS at Massachusetts General Hospital and Beth Israel Deaconess Medical Center. Interventions None Measurements and Main Results AKI was defined as meeting the “Risk” category according to modified Risk Injury Failure Loss End-stage (RIFLE) criteria based on Creatinine (Cr) and glomerular filtration rate (GFR) since urine output was only available on the day of ICU admission. BMI was calculated from height and weight on ICU admission. The prevalence of AKI increased significantly with increasing weight (p = 0.01). The odds of AKI were twice in obese and severely obese patients compared to normal BMI after adjusting for predictors of AKI (age, diabetes, APACHE III, aspiration, vasopressor use, and thrombocytopenia (platelets ≤ 80,000/mm3)). After adjusting for the same predictors, BMI was significantly associated with AKI (ORadj 1.20 per 5 kg/m2 increase in BMI, 95%CI 1.07–1.33). On multivariate analysis, AKI was associated with increased ARDS mortality (ORadj 2.76, 95%CI 1.72–4.42) while BMI was associated with decreased mortality (ORadj 0.81 per 5 kg/m2 increase in BMI, 95%CI 0.71–0.93) after adjusting for mortality predictors. Conclusions In ARDS patients, obesity is associated with increased development of AKI that is not completely explained by severity of illness or shock. While increased BMI is associated with decreased mortality, AKI remained associated with higher mortality even after adjusting for BMI.