Bioenergetic Crisis in ICU-Acquired Weakness Gene Signatures Was Associated With Sepsis-Related Mortality: A Brief Report.
Ontology highlight
ABSTRACT: Design
Observational study using differential gene expression analysis.Setting
Publicly available gene expression profile GSE54514, single-center medical and surgical ICU.Patients
Patients with primary bacteremia- and respiratory-triggered sepsis including 8 nonsurvivors and 13 survivors who were 18 years old and older and admitted to ICU.Measurements and main results
Among validated 526 ICUAW gene signatures, differential gene expression analysis controlling for age identified 38 significantly expressed genes between nonsurvivors and survivors. Functional enrichment analysis of differentially expressed ICUAW genes identified impaired cadherin binding, sarcomere formation, and energy metabolism among nonsurvivors.Conclusions
Our findings demonstrated a biological association between sepsis-related mortality and ICUAW signatures in the early phase of sepsis. Defects in energy metabolism and muscle fiber formation were associated with sepsis-related mortality.
SUBMITTER: Kobara S
PROVIDER: S-EPMC9760600 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
Publications
Bioenergetic Crisis in ICU-Acquired Weakness Gene Signatures Was Associated With Sepsis-Related Mortality: A Brief Report.
Kobara Seibi S Rad Milad G MG Grunwell Jocelyn R JR Coopersmith Craig M CM Kamaleswaran Rishikesan R
Critical care explorations 20221214 12
To investigate the relationship between ICU-acquired weakness (ICUAW) signatures and sepsis-related mortality using gene expression from the blood within 24 hours of sepsis onset.<h4>Design</h4>Observational study using differential gene expression analysis.<h4>Setting</h4>Publicly available gene expression profile GSE54514, single-center medical and surgical ICU.<h4>Patients</h4>Patients with primary bacteremia- and respiratory-triggered sepsis including 8 nonsurvivors and 13 survivors who were ...[more]
Similar Datasets
Project description:Survivorship after critical illness is an increasingly important health-care concern as ICU use continues to increase while ICU mortality is decreasing. Survivors of critical illness experience marked disability and impairments in physical and cognitive function that persist for years after their initial ICU stay. Newfound impairment is associated with increased health-care costs and use, reductions in health-related quality of life, and prolonged unemployment. Weakness, critical illness neuropathy and/or myopathy, and muscle atrophy are common in patients who are critically ill, with up to 80% of patients admitted to the ICU developing some form of neuromuscular dysfunction. ICU-acquired weakness (ICUAW) is associated with longer durations of mechanical ventilation and hospitalization, along with greater functional impairment for survivors. Although there is increasing recognition of ICUAW as a clinical entity, significant knowledge gaps exist concerning identifying patients at high risk for its development and understanding its role in long-term outcomes after critical illness. This review addresses the epidemiologic and pathophysiologic aspects of ICUAW; highlights the diagnostic challenges associated with its diagnosis in patients who are critically ill; and proposes, to our knowledge, a novel strategy for identifying ICUAW.
| S-EPMC5103015 | biostudies-literature
Project description: Not available
| S-EPMC3642827 | biostudies-literature
Project description:ICUs are experiencing an epidemic of patients with acute brain dysfunction (delirium) and weakness, both associated with increased mortality and long-term disability. These conditions are commonly acquired in the ICU and are often initiated or exacerbated by sedation and ventilation decisions and management. Despite > 10 years of evidence revealing the hazards of delirium, the quality chasm between current and ideal processes of care continues to exist. Monitoring of delirium and sedation levels remains inconsistent. In addition, sedation, ventilation, and physical therapy practices proven successful at reducing the frequency and severity of adverse outcomes are not routinely practiced. In this article, we advocate for the adoption and implementation of a standard bundle of ICU measures with great potential to reduce the burden of ICU-acquired delirium and weakness. Individual components of this bundle are evidence based and can help standardize communication, improve interdisciplinary care, reduce mortality, and improve cognitive and functional outcomes. We refer to this as the "ABCDE bundle," for awakening and breathing coordination, delirium monitoring, and exercise/early mobility. This evidence-based bundle of practices will build a bridge across the current quality chasm from the "front end" to the "back end" of critical care and toward improved cognitive and functional outcomes for ICU survivors.
| S-EPMC4694109 | biostudies-other
Project description:BackgroundVasoactive medications are commonly used in the treatment of critically ill patients, but their impact on the development of ICU-acquired weakness is not well described. The objective of this study is to evaluate the relationship between vasoactive medication use and the outcome of ICU-acquired weakness.MethodsThis is a secondary analysis of mechanically ventilated patients (N = 172) enrolled in a randomized clinical trial of early occupational and physical therapy vs conventional therapy, which evaluated the end point of ICU-acquired weakness on hospital discharge. Patients underwent bedside muscle strength testing by a therapist blinded to study allocation to evaluate for ICU-acquired weakness. The effects of vasoactive medication use on the incidence of ICU-acquired weakness in this population were assessed.ResultsOn logistic regression analysis, the use of vasoactive medications increased the odds of developing ICU-acquired weakness (odds ratio [OR], 3.2; P = .01) independent of all other established risk factors for weakness. Duration of vasoactive medication use (in days) (OR, 1.35; P = .004) and cumulative norepinephrine dose (μg/kg/d) (OR, 1.01; P = .02) (but not vasopressin or phenylephrine) were also independently associated with the outcome of ICU-acquired weakness.ConclusionsIn mechanically ventilated patients enrolled in a randomized clinical trial of early mobilization, the use of vasoactive medications was independently associated with the development of ICU-acquired weakness. Prospective trials to further evaluate this relationship are merited.Trial registryClinicalTrials.gov; No.: NCT01777035; URL: www.clinicaltrials.gov.
| S-EPMC6689081 | biostudies-literature
Project description:INTRODUCTION: Early diagnosis of intensive care unit - acquired weakness (ICU-AW) using the current reference standard, that is, assessment of muscle strength, is often hampered due to impaired consciousness. Biological markers could solve this problem but have been scarcely investigated. We hypothesized that plasma levels of neurofilaments are elevated in ICU-AW and can diagnose ICU-AW before muscle strength assessment is possible. METHODS: For this prospective observational cohort study, neurofilament levels were measured using ELISA (NfHSMI35 antibody) in daily plasma samples (index test). When patients were awake and attentive, ICU-AW was diagnosed using the Medical Research Council scale (reference standard). Differences and discriminative power (using the area under the receiver operating characteristic curve; AUC) of highest and cumulative (calculated using the area under the neurofilament curve) neurofilament levels were investigated in relation to the moment of muscle strength assessment for each patient. RESULTS: Both the index test and reference standard were available for 77 ICU patients. A total of 18 patients (23%) fulfilled the clinical criteria for ICU-AW. Peak neurofilament levels were higher in patients with ICU-AW and had good discriminative power (AUC: 0.85; 95% CI: 0.72 to 0.97). However, neurofilament levels did not peak before muscle strength assessment was possible. Highest or cumulative neurofilament levels measured before muscle strength assessment could not diagnose ICU-AW (AUC 0.59; 95% CI 0.37 to 0.80 and AUC 0.57; 95% CI 0.32 to 0.81, respectively). CONCLUSIONS: Plasma neurofilament levels are raised in ICU-AW and may serve as a biological marker for ICU-AW. However, our study suggests that an early diagnosis of ICU-AW, before muscle strength assessment, is not possible using neurofilament levels in plasma.
| S-EPMC4057240 | biostudies-literature
Project description:ObjectiveThe early use of neuromuscular electrical stimulation (NMES) to prevent intensive care unit-acquired weakness (ICU-AW) in critical patients is still a controversial topic. We conducted a systematic review to clarify the effectiveness of NMES in preventing ICU-AW.MethodsThe Cochrane Library, PubMed, EMBASE, MEDLINE, Web of Science, Ovid, CNKI, Wanfang, VIP, China Biology Medicine disc (CBMdisc) and other databases were searched for randomized controlled trials on the influence of NMES on ICU-AW. The studies were selected according to the inclusion and exclusion criteria. After data and quality were evaluated, a meta-analysis was performed by RevMan 5.3 software.ResultsA total of 11 randomized controlled trials with 576 patients were included. The meta-analysis results showed that NMES can improve muscle strength [MD = 1.78, 95% CI (0.44, 3.12, P = 0.009); shorten the mechanical ventilation (MV) time [SMD = -0.65, 95% CI (-1.03, -0.27, P = 0.001], ICU length of stay [MD = -3.41, 95% CI (-4.58, -4.24), P < 0.001], and total length of stay [MD = -3.97, 95% CI (-6.89, -1.06, P = 0.008]; improve the ability of patients to perform activities of daily living [SMD = 0.9, 95% CI (0.45, 1.35), P = 0.001]; and increase walking distance [MD = 239.03, 95% CI (179.22298.85), P < 0.001]. However, there is no evidence indicating that NMES can improve the functional status of ICU patients during hospitalization, promote the early awakening of patients or reduce mortality (P > 0.05).ConclusionEarly implementation of the NMES intervention in ICU patients can prevent ICU-AW and improve their quality of life by enhancing their muscle strength and shortening the MV duration, length of stay in the ICU and total length of stay in the hospital.
| S-EPMC7355203 | biostudies-literature
Project description:BACKGROUND:Intensive care unit (ICU)-acquired weakness and diaphragm dysfunction are frequent conditions, both associated with poor prognosis in critically ill patients. While it is well established that ICU-acquired weakness severely impairs long-term prognosis, the association of diaphragm dysfunction with this outcome has never been reported. This study investigated whether diaphragm dysfunction is associated with negative long-term outcomes and whether the coexistence of diaphragm dysfunction and ICU-acquired weakness has a particular association with 2-year survival and health-related quality of life (HRQOL). METHODS:This study is an ancillary study derived from an observational cohort study. Patients under mechanical ventilation were enrolled at the time of their first spontaneous breathing trial. Diaphragm dysfunction was defined by tracheal pressure generated by phrenic nerve stimulation < 11 cmH2O and ICU-acquired weakness was defined by Medical Research Council (MRC) score < 48. HRQOL was evaluated with the SF-36 questionnaire. RESULTS:Sixty-nine of the 76 patients enrolled in the original study were included in the survival analysis and 40 were interviewed. Overall 2-year survival was 67% (46/69): 64% (29/45) in patients with diaphragm dysfunction, 71% (17/24) in patients without diaphragm dysfunction, 46% (11/24) in patients with ICU-acquired weakness and 76% (34/45) in patients without ICU-acquired weakness. Patients with concomitant diaphragm dysfunction and ICU-acquired weakness had a poorer outcome with a 2-year survival rate of 36% (5/14) compared to patients without diaphragm function and ICU-acquired weakness [79% (11/14) (p < 0.01)]. Health-related quality of life was not influenced by the presence of ICU-acquired weakness, diaphragm dysfunction or their coexistence. CONCLUSIONS:ICU-acquired weakness but not diaphragm dysfunction was associated with a poor 2-year survival of critically ill patients.
| S-EPMC6942110 | biostudies-literature
Project description:Background : The aim of this study is to improve our understanding of the mechanisms underlying the role of sepsis in the limb muscles of ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factor triggering AQM that is endotoxin-induced sepsis. Results : An increased expression of genes involved in chemokine activity and transcriptional regulation. A decreased expression in genes regulating heat shock proteins, cytoskeletal & sarcomeric and oxidative stress response were also apparent. Therefore, it appears that sepsis has an additive deleterious role in acute quadriplegic myopathy. Sepsis-induced molecular mechanisms involving chemokine/innate immunity and heat shock proteins are forwarded as probable mechanisms underlying the decreased force generating capacity. Conclusions : This sepsis had significant effect on biceps femoris muscle force-generation capacity but not on fiber size. However, significant differences were observed between the MV and MV+SEP in the transcriptional regulation of an increased expression of genes involved in chemokine activity genes like MCP-1 and transcriptional regulation genes like JUNB, STAT3 and BHLHB2. A decreased expression in genes regulating heat shock proteins like HSP 90, HSP 70 and αB-crystallin, cytoskeletal & sarcomeric like MAP1A, MyBP-C1 and MYH7 and oxidative stress response like SRXN1 and SOD2 were also apparent. Therefore, it appears that sepsis has an additive negative role in acute quadriplegic myopathy. Four female domestic piglets (Sus scrofa, average body weight 25.5 kg) were used in this study. Piglets were immobilized by anesthesia and mechanically ventilated via a tracheotomy for a period of five days. During this study period, the animals were sedated using isoflurane inhalation (Abbott Laboratories, Chicago, Il, USA, 0.8 – 1.3% end-tidal concentration) supplemented by intravenous bolus doses of morphine and ketamine as needed. Core body temperature (blood) was maintained in the range of 38.5 – 40°C by a servo controlled heating pad. The animals received intravenous crystalloid fluid (Ringeracetat) to maintain stable blood pressure and urinary output and a glucose infusion (Rehydrex, Fresenius Kabi, Stockholm, Sweden, 25 mg glucose /mL) in the range of 0.5 – 1.5 mg/kg/minute to decrease the effects of catabolism. Each animal received prophylactic streptomycin 750 mg/d and bensylpenicillin 600 mg/d (Streptocillin Vet, Boeringer-Ingelheim, Hellerup, Denmark). Arterial blood gas analysis as well as electrolytes and blood glucose levels were monitored regularly and kept in the normal range throughout the study period. A neuromuscular blocking agent (NMBA) was administered as a continuous infusion of pancuronium bromide 0.1mg/kg/h (Pavolun; Organon, Boxtel, The Netherlands) for 5days while a corticosteroid (CS) was given as bolus doses of betamethasone 0.1 mg/kg (Betapred; GSK, Slona, Sweden) twice daily for 5days. Endotoxemia was induced by a continuous infusion of Escherichia coli endotoxin, serotype O26:B6 (Sigma Labkemi, Stockholm, Sweden) at 36 µg/kg/h for 1h. Key words : Treatment, immobilization, muscle function.
2011-10-18 | E-GEOD-33037 | biostudies-arrayexpress
Project description:Background : The aim of this study is to improve our understanding of the mechanisms underlying the role of sepsis in the limb muscles of ICU patients with acute quadriplegic myopathy (AQM) by using a unique porcine ICU model, i.e., 5-day longitudinal experiments where animals are sedated, mechanically ventilated and exposed to factor triggering AQM that is endotoxin-induced sepsis. Results : An increased expression of genes involved in chemokine activity and transcriptional regulation. A decreased expression in genes regulating heat shock proteins, cytoskeletal & sarcomeric and oxidative stress response were also apparent. Therefore, it appears that sepsis has an additive deleterious role in acute quadriplegic myopathy. Sepsis-induced molecular mechanisms involving chemokine/innate immunity and heat shock proteins are forwarded as probable mechanisms underlying the decreased force generating capacity. Conclusions : This sepsis had significant effect on biceps femoris muscle force-generation capacity but not on fiber size. However, significant differences were observed between the MV and MV+SEP in the transcriptional regulation of an increased expression of genes involved in chemokine activity genes like MCP-1 and transcriptional regulation genes like JUNB, STAT3 and BHLHB2. A decreased expression in genes regulating heat shock proteins like HSP 90, HSP 70 and αB-crystallin, cytoskeletal & sarcomeric like MAP1A, MyBP-C1 and MYH7 and oxidative stress response like SRXN1 and SOD2 were also apparent. Therefore, it appears that sepsis has an additive negative role in acute quadriplegic myopathy.
2011-10-19 | GSE33037 | GEO
Project description:Over the last 10 years we have significantly reduced hospital mortality from sepsis and critical illness. However, the evidence reveals that over the same period we have tripled the number of patients being sent to rehabilitation settings. Further, given that as many as half of the deaths in the first year following ICU admission occur post ICU discharge, it is unclear how many of these patients ever returned home. For those who do survive, the latest data indicate that 50-70% of ICU "survivors" will suffer cognitive impairment and 60-80% of "survivors" will suffer functional impairment or ICU-acquired weakness (ICU-AW). These observations demand that we as intensive care providers ask the following questions: "Are we creating survivors ... or are we creating victims?" and "Do we accomplish 'Pyrrhic Victories' in the ICU?" Interventions to address ICU-AW must have a renewed focus on optimal nutrition, anabolic/anticatabolic strategies, and in the future employ the personalized muscle and exercise evaluation techniques utilized by elite athletes to optimize performance. Specifically, strategies must include optimal protein delivery (1.2-2.0 g/kg/day), as an athlete would routinely employ. However, as is clear in elite sports performance, optimal nutrition is fundamental but alone is often not enough. We know burn patients can remain catabolic for 2 years post burn; thus, anticatabolic agents (i.e., beta-blockers) and anabolic agents (i.e., oxandrolone) will probably also be essential. In the near future, evaluation techniques such as assessing lean body mass at the bedside using ultrasound to determine nutritional status and ultrasound-measured muscle glycogen as a marker of muscle injury and recovery could be utilized to help find the transition from the acute phase of critical illness to the recovery phase. Finally, exercise physiology testing that evaluates muscle substrate utilization during exercise can be used to diagnose muscle mitochondrial dysfunction and to guide a personalized ideal heart rate, assisting in recovery of muscle mitochondrial function and functional endurance post ICU. In the end, future ICU-AW research must focus on using a combination of modern performance-enhancing nutrition, anticatabolic/anabolic interventions, and muscle/exercise testing so we can begin to create more "survivors" and fewer victims post ICU care.
| S-EPMC4699141 | biostudies-literature