OBJECTIVES::
Measurements of extravascular lung water (EVLW) correlate to the degree of pulmonary edema and have substantial prognostic information in critically ill patients. Prior studies using single indicator thermodilution have reported that 21% to 35% of patients with clinical acute respiratory distress syndrome (ARDS) have normal EVLW (<10 mL/kg). Given that lung size is independent of actual body weight, we sought to determine whether indexing EVLW to predicted or adjusted body weight affects the frequency of increased EVLW in patients with ARDS. DESIGN:: Prospective, observational cohort study. SETTING:: Medical and surgical intensive care units at two academic hospitals. PATIENTS:: Thirty patients within 72 hrs of meeting American-European Consensus Conference definition of ARDS and 14 severe sepsis patients without ARDS. INTERVENTIONS:: None. MEASUREMENT AND MAIN RESULTS:: EVLW was measured for 7 days by PiCCO transpulmonary thermodilution; 225 measurements of EVLW indexed to actual body weight (ActBW) were compared with EVLW indexed to predicted body weight (PBW) and adjusted body weight (AdjBW). Mean EVLW indexed to ActBW was 12.7 mg/kg for ARDS patients and 7.8 mg/kg for non-ARDS sepsis patients (p < .0001). In all patients, EVLW increased an average of 1.1 ± 2.1 mL/kg when indexed to AdjBW and 2.0 ± 4.1 mL/kg when indexed to PBW. Indexing EVLW to PBW or AdjBW increased the proportion of ARDS patients with elevated EVLW (each p < .05) without increasing the frequency of elevated EVLW in non-ARDS patients. EVLW indexed to PBW had a stronger correlation to Lung Injury Score (r = .39 vs. r = .17) and Pao2/Fio2 ratio (r = .25 vs. r = .10) than did EVLW indexed to ActBW. CONCLUSIONS:: Indexing EVLW to PBW or AdjBW reduces the number of ARDS patients with normal EVLW and correlates better to Lung Injury Score and oxygenation than using ActBW. Studies are needed to confirm the presumed superiority of this method for diagnosing ARDS and to determine the clinical treatment implications.
Introduction
Several studies have shown a correlation between body mass index (BMI) and both the development of critical illness and adverse outcomes in critically ill patients. The goal of our study was to examine this relationship prospectively with particular attention to the influence of concomitant diabetes mellitus (DM).
Methods
We analyzed data from 15,408 participants in the Atherosclerosis Risk in Communities (ARIC) study for this analysis. BMI and the presence of DM were defined at baseline. We defined 'acute organ failure' as those subjects who met a standard definition with diagnostic codes abstracted from hospitalization records. Outcomes assessed included the following: risk of the development of acute organ failure within three years of the baseline examination; in-hospital death while ill with acute organ failure; and death at three years among all subjects and among those with acute organ failure.
Results
At baseline, participants with a BMI of at least 30 were more likely than those in lower BMI categories to have DM (22.4% versus 7.9%, p < 0.01). Overall, BMI was not a significant predictor of developing acute organ failure. The risk for developing acute organ failure was increased among subjects with DM in comparison with those without DM (2.4% versus 0.7%, p < 0.01). Among subjects with organ failure, both in-hospital mortality (46.5% versus 12.2%, p < 0.01) and 3-year mortality (51.2% versus 21.1%, p < 0.01) was higher in subjects with DM.
Conclusion
Our findings suggest that obesity by itself is not a significant predictor of either acute organ failure or death during or after acute organ failure in this cohort. However, the presence of DM, which is related to obesity, is a strong predictor of both acute organ failure and death after acute organ failure.
Objectives High-dose vitamin D3increases plasma total 25-hydroxyvitamin D [25(OH)D] in critically ill, ventilated patients; however, to our knowledge, the effect on plasma levels of free (nonprotein-bound) 25(OH)D has not been investigated in critical illness. Moreover, the relationship of free 25(OH)D and the regulation of endogenous antimicrobial peptides (AMPs) remains unknown. The aims of this study were to determine in critically ill adults with respiratory failure the effect of previous high-dose regimens of vitamin D3on free 25(OH)D concentrations, the relationship of free 25(OH)D with circulating cathelicidin (LL-37) and human beta-defensin-2 (hBD-2), and the associations between plasma levels of free 25(OH)D and these AMPs to alveolar macrophage phagocytosis function. Methods In a double blind, randomized controlled trial, critically ill ventilator-dependent adults (N = 30) received enteral vitamin D3(250,000 or 500,000 IU total over 5 d) or placebo. Plasma was obtained serially for concentrations of free 25(OH)D, LL-37, hBD-2, and expression of peripheral blood mononuclear cell human cationic antimicrobial protein (hCAP18) mRNA. Total 25(OH)D and LL-37 concentrations and alveolar macrophage phagocytosis were determined in bronchoalveolar lavage fluid. Results Plasma concentrations of free 25(OH)D over time were correlated with total 25(OH)D levels (r= 0.82; P < 0.001). The increase in free 25(OH)D was greater with the 500 000 IU vitamin D3dose than with the lower dose. The percent change in mRNA expression of hCAP18 was positively associated with percent change in free 25(OH)D at days 7 and 14 (ρ = 0.48; P = 0.04 and ρ = 0.59; P = 0.03, respectively). Additionally, plasma LL-37 levels correlated with the percentage of alveolar macrophages exhibiting phagocytosis (ρ = 0.51; P = 0.04). Conclusions The present study found a dose-related increase in plasma free-25(OH)D levels, which was associated with increasing circulating mRNA expression of hCAP18 over time. There were no correlations between changes in total and free 25(OH)D against plasma LL-37 and hBD-2 concentrations. Larger studies appear warranted to determine the impact of high-dose vitamin D3administration on endogenous AMPs.
Sepsis is one of the most common conditions encountered in the intensive care unit and is the 10th leading cause of death overall in the United States. Both long-term survival and health-related quality of life are reduced in survivors of sepsis, yet there is little knowledge of the effect of sepsis-specific interventions on either long-term survival or health-related quality of life. The present article discusses the importance of studying health-related quality of life as it relates to sepsis management strategies, particularly in the context of pharmacologic therapy with recombinant human activated protein C.
Objective
Lung infections are a leading cause of death in HIV-infected individuals. Measuring redox in HIV-infected individuals may identify those with chronic oxidative stress who are at increased risk for lung infection. We sought to estimate the association between HIV infection and oxidative stress in the lung, as reflected by decreased levels of glutathione and cysteine in the epithelial lining fluid.
Methods
Bronchoalveolar lavage (BAL) fluid was collected from healthy HIV-infected subjects and controls. Individuals were excluded if they had evidence of major medical co-morbidities, were malnourished or smoked cigarettes.
Results
We enrolled 22 otherwise healthy HIV and 21 non-HIV subjects. Among the HIV-infected subjects, 72.7% were on anti-retroviral therapy (ART) with a median CD4 count of 438 (279.8–599) and viral load of 0 (0–1.0) log copies/mL. There were no significant differences in median BAL fluid glutathione and cysteine levels between HIV and HIV-uninfected subjects. However, BAL glutathione was significantly higher in HIV-infected subjects on anti-retroviral therapy (ART) compared to those not on ART [367.4 (102–965.3) nM vs. 30.8 (1.0–112.1) nM, p = 0.008]. Further, HIV infection with ART was associated with an OR of 2.02 for increased BAL glutathione when adjusted for age and body mass index, whereas HIV infection without ART was associated with an OR of 2.17 for decreased BAL glutathione.
Conclusion
HIV infection without ART was associated with increased oxidative stress, as reflected by decreased alveolar glutathione levels, in otherwise healthy HIV-infected individuals. Further study needs to be done identify predictors of lung health in HIV and to address the role of ART in improving lung immunity.
by
Manu Shankar-Hari;
Gary S. Phillips;
Mitchell L. Levy;
Christopher W. Seymour;
Vincent X. Liu;
Clifford S. Deutschman;
Derek C. Angus;
Gordon D. Rubenfeld;
Mervyn Singer;
Greg Martin
Importance Septic shock currently refers to a state of acute circulatory failure associated with infection. Emerging biological insights and reported variation in epidemiology challenge the validity of this definition.
Objective To develop a new definition and clinical criteria for identifying septic shock in adults.
Design, Setting, and Participants The Society of Critical Care Medicine and the European Society of Intensive Care Medicine convened a task force (19 participants) to revise current sepsis/septic shock definitions. Three sets of studies were conducted: (1) a systematic review and meta-analysis of observational studies in adults published between January 1, 1992, and December 25, 2015, to determine clinical criteria currently reported to identify septic shock and inform the Delphi process; (2) a Delphi study among the task force comprising 3 surveys and discussions of results from the systematic review, surveys, and cohort studies to achieve consensus on a new septic shock definition and clinical criteria; and (3) cohort studies to test variables identified by the Delphi process using Surviving Sepsis Campaign (SSC) (2005-2010; n = 28 150), University of Pittsburgh Medical Center (UPMC) (2010-2012; n = 1 309 025), and Kaiser Permanente Northern California (KPNC) (2009-2013; n = 1 847 165) electronic health record (EHR) data sets.
Main Outcomes and Measures Evidence for and agreement on septic shock definitions and criteria.
Results The systematic review identified 44 studies reporting septic shock outcomes (total of 166 479 patients) from a total of 92 sepsis epidemiology studies reporting different cutoffs and combinations for blood pressure (BP), fluid resuscitation, vasopressors, serum lactate level, and base deficit to identify septic shock. The septic shock–associated crude mortality was 46.5% (95% CI, 42.7%-50.3%), with significant between-study statistical heterogeneity (I2 = 99.5%; τ2 = 182.5; P < .001). The Delphi process identified hypotension, serum lactate level, and vasopressor therapy as variables to test using cohort studies. Based on these 3 variables alone or in combination, 6 patient groups were generated. Examination of the SSC database demonstrated that the patient group requiring vasopressors to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L (18 mg/dL) after fluid resuscitation had a significantly higher mortality (42.3% [95% CI, 41.2%-43.3%]) in risk-adjusted comparisons with the other 5 groups derived using either serum lactate level greater than 2 mmol/L alone or combinations of hypotension, vasopressors, and serum lactate level 2 mmol/L or lower. These findings were validated in the UPMC and KPNC data sets.
Conclusions and Relevance Based on a consensus process using results from a systematic review, surveys, and cohort studies, septic shock is defined as a subset of sepsis in which underlying circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than sepsis alone. Adult patients with septic shock can be identified using the clinical criteria of hypotension requiring vasopressor therapy to maintain mean BP 65 mm Hg or greater and having a serum lactate level greater than 2 mmol/L after adequate fluid resuscitation.
The growing basic and clinical investigations into the extraskeletal effects of vitamin D have revealed roles in the functioning of the immune system, generating interesting questions about this nutrient's connections to sepsis. This article briefly reviews the current science of the function of vitamin D in the immune system as well as the emerging clinical literature regarding its associations with respiratory infections, sepsis, and critical illness. Finally, we offer views on the potential future directions for research in the field by outlining potential relevant scenarios and outcomes.
Medical databases serve a critical function in healthcare, including the areas of patient care, administration, research and education. The quality and breadth of information collected into existing databases varies tremendously, between databases, between institutions and between national boundaries. The field of critical care medicine could be advanced substantially by the development of comprehensive and accurate databases.
Introduction
Diabetes mellitus (DM) is one of the most common chronic co-morbid medical conditions in the USA and is frequently present in patients with sepsis. Previous studies reported that people with DM and severe sepsis are less likely to develop acute lung injury (ALI). We sought to determine whether organ dysfunction differed between people with and without DM and sepsis.
Methods
Using the National Hospital Discharge Survey US, sepsis cases from 1979 to 2003 were integrated with DM prevalence from the Centers for Disease Control and Prevention (CDC) Diabetes Surveillance System.
Results
During the study period 930 million acute-care hospitalisations and 14.3 million people with DM were identified. Sepsis occurred in 12.5 million hospitalisations and DM was present in 17% of patients with sepsis. In the population, acute respiratory failure was the most common organ dysfunction (13%) followed by acute renal failure (6%). People with DM were less likely to develop acute respiratory failure (9% vs. 14%, p < 0.05) and more likely to develop acute renal failure (13% vs. 7%, p < 0.05). Of people with DM and sepsis, 27% had a respiratory source of infection compared with 34% in people with no DM (p < 0.05). Among patients with a pulmonary source of sepsis, 16% of those with DM and 23% of those with no DM developed acute respiratory failure (p < 0.05); in non-pulmonary sepsis acute respiratory failure occurred in 6% of people with DM and 10% in those with no DM (p < 0.05).
Conclusions
In sepsis, people with diabetes are less likely to develop acute respiratory failure, irrespective of source of infection. Future studies should determine the relationship of these findings to reduced risk of ALI in people with DM and causative mechanisms.