Two Decades of Mortality Trends Among Patients With Severe Sepsis: A Comparative Meta-Analysis.
1The Pulmonary Center, Boston University School of Medicine, Boston, MA. 2Division of Pulmonary, Allergy, and Critical Care Medicine Internal Medicine, Boston Medical Center, Boston, MA. 3Department of Medicine, Boston Medical Center, Boston, MA. 4Center for Healthcare Organization & Implementation Research Edith Nourse Rogers Memorial VA Hospital, Bedford, MA. 5The Dartmouth Institute for Health Policy and Clinical Practice, Dartmouth Medical School, Hanover, NH. Critical care medicine
(Impact Factor: 6.31).
11/2013; 42(3). DOI: 10.1097/CCM.0000000000000026
Trends in severe sepsis mortality derived from administrative data may be biased by changing International Classification of Diseases, 9th Revision, Clinical Modification, coding practices. We sought to determine temporal trends in severe sepsis mortality using clinical trial data that does not rely on International Classification of Diseases, Ninth Revision, Clinical Modification coding and compare mortality trends in trial data with those observed from administrative data.
We searched MEDLINE for multicenter randomized trials that enrolled patients with severe sepsis from 1991 to 2009. We calculated standardized mortality ratios for each trial from observed 28-day mortality of usual care participants and predicted mortality from severity-of-illness scores. To compare mortality trends from clinical trials to administrative data, we identified adult severe sepsis hospitalizations in the Nationwide Inpatient Sample, 1993-2009, using two previously validated algorithms.
Patients with severe sepsis or septic shock.
Of 3,244 potentially eligible articles, we included 36 multicenter severe sepsis trials, with a total of 14,418 participants in a usual care arm. Participants with severe sepsis receiving usual care had a 28-day mortality of 33.2%. Observed mortality decreased 3.0% annually (95% CI, 0.8%-5.0%; p = 0.009), decreasing from 46.9% (standardized mortality ratio 0.94; 95% CI, 0.86-1.03) during years 1991-1995 to 29% (standardized mortality ratio 0.53; 95% CI, 0.50-0.57) during years 2006-2009 (3.0% annual change). Trends in hospital mortality among patients with severe sepsis identified from administrative data (Angus definition, 4.7% annual change; 95% CI, 4.1%-5.3%; p = 0.69 and Martin definition, 3.5% annual change; 95% CI, 3.0%-4.1%; p = 0.97) were similar to trends identified from clinical trials.
Since 1991, patients with severe sepsis enrolled in usual care arms of multicenter randomized trials have experienced decreasing mortality. The mortality trends identified in clinical trial participants appear similar to those identified using administrative data and support the use of administrative data to monitor mortality trends in patients with severe sepsis.
Available from: Sunil Belur Nagaraj
- "The survival rate of ICU patients has improved dramatically over the past several decades.   However, up to 50% of ICU survivors go on to develop life-altering long-term cognitive impairments . Delirium, an acute neuropsychiatric syndrome characterized by fluctuations in arousal and decreased awareness, attention, and cognition, is a major risk factor for post-ICU cognitive impairment, and may be prevalent in up to 75% of critically ill patients . "
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ABSTRACT: Millions of patients are admitted each year to intensive care units (ICUs) in the United States. A significant fraction of ICU survivors develop lifelong cognitive impairment, incurring tremendous financial and societal costs. Delirium, a state of impaired awareness, attention and cognition that frequently develops during ICU care, is a major risk factor for post-ICU cognitive impairment. Recent studies suggest that patients experiencing electroencephalogram (EEG) burst suppression have higher rates of mortality and are more likely to develop delirium than patients who do not experience burst suppression. Burst suppression is typically associated with coma and deep levels of anesthesia or hypothermia, and is defined clinically as an alternating pattern of high-amplitude " burst " periods interrupted by sustained low-amplitude " suppression " periods. Here we describe a clustering method to analyze EEG spectra during burst and suppression periods. We used this method to identify a set of distinct spectral patterns in the EEG during burst and suppression periods in critically ill patients. These patterns correlate with level of patient sedation, quantified in terms of sedative infusion rates and clinical sedation scores. This analysis suggests that EEG burst suppression in critically ill patients may not be a single state, but instead may reflect a plurality of states whose specific dynamics relate to a patient's underlying brain function.
Available from: Andreas Barth
- "In the United States, sepsis is one of the top ten leading causes of mortality . Although adjusted in-hospital mortality has decreased gradually (2-3% per year) according to a recent report  , sepsis associated mortality remained high, from 50/100,000 to 75/100,000  . It was even higher when sepsis was accompanied by organ dysfunction, ranging from 23% to 58% with dysfunction of one organ    and increasing to 77.4% when three or more organs had failure . "
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Sepsis is a leading cause of mortality in intensive care units worldwide. A better understanding of the blood systems response to sepsis should expedite the identification of biomarkers for early diagnosis and therapeutic interventions.
We analyzed microarray studies whose data is available from the GEO repository and which were performed on the whole blood of septic patients and normal controls.
We identified 6 cohorts consisting of 450 individuals (sepsis = 323, control = 127) providing genome-wide messenger RNA (mRNA) expression data. Through meta-analysis we found the "Lysosome" and "Cytoskeleton" pathways were upregulated in human sepsis patients relative to controls, in addition to previously known signaling pathways (including MAPK, TLR). The key regulatory genes in the "Lysosome" pathway include lysosomal acid hydrolases (e.g., protease cathepsin A, D) as well as the major (LAMP1, 2) and minor (SORT1, LAPTM4B) membrane proteins. In contrast, pathways related to "Ribosome", "Spliceosome" and "Cell adhesion molecules" were found to be downregulated, along with known pathways for immune dysfunction. Overall, our study revealed distinct mRNA activation profiles and protein-protein interaction networks in blood of human sepsis.
Our findings suggest that aberrant mRNA expression in the lysosome and cytoskeleton pathways may play a pivotal role in the molecular pathobiology of human sepsis.
Available from: Fabrizio Monaco
- "Acute organ dysfunction due to severe infection is associated with a high mortality rate . The mortality rate of patients with septic shock is decreasing  , but still remains high, despite widespread adoption of international sepsis guidelines . There are still several doubts about medical therapy in septic patients. "
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ABSTRACT: There is controversy about the use of inotropes in the treatment of severe sepsis and septic shock. The objective of this study was to evaluate if levosimendan, as compared with standard inotropic therapy (eg, dobutamine), reduces mortality in septic patients.
BioMedCentral, PubMed, EMBASE, and the Cochrane Central Register were searched for pertinent studies, up to 1st May 2015. Randomized trials on the use of levosimendan in patients with severe sepsis and septic shock were included if reporting mortality data. The primary outcome was mortality, whereas secondary outcomes were blood lactate, cardiac index, total fluid infused, norepinephrine dosage, and mean arterial pressure.
Seven studies for a total of 246 patients were included in the analysis. Levosimendan was associated with significantly reduced mortality compared with standard inotropic therapy (59/125 [47%] in the levosimendan group and 74/121 [61%] in the control group; risk difference = -0.14, risk ratio = 0.79 [0.63-0.98], P for effect = .03, I(2) = 0%, numbers needed to treat = 7). Blood lactate was significantly reduced in the levosimendan group, whereas cardiac index and total fluid infused were significantly higher in the levosimendan group. No difference in mean arterial pressure and norepinephrine usage was noted.
In patients with severe sepsis and septic shock, levosimendan is associated with a significant reduction in mortality compared with standard inotropic therapy. A large ongoing multicenter randomized trial will have to confirm these findings.
Copyright © 2015. Published by Elsevier Inc.
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