Reducing iatrogenic risks: ICU-acquired delirium and weakness--crossing the quality chasm.
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ABSTRACT:
SUBMITTER: Vasilevskis EE
PROVIDER: S-EPMC4694109 | biostudies-other | 2010 Nov
REPOSITORIES: biostudies-other
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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: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: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: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: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
Project description:BACKGROUND:Neuroinflammation is thought to play an important role in the pathogenesis of ICU-acquired delirium, but the association between inflammatory and brain-specific proteins and ICU delirium is poor. We investigated whether or not serial determinations of markers may improve this association. METHODS:Critically ill patients with a high risk of ICU delirium and with an ICU length of stay of at least 6 days were included in the study. Blood was drawn on days 1, 2, 4 and 6 after ICU admission and analyzed for different markers of inflammation and several brain proteins. Differences in courses over time prior to and following the onset of delirium and absolute differences over time were analyzed in patients with and without delirium using repeated measurement analysis of variance. In addition, a cross-sectional analysis of levels of these markers before the first onset of delirium was performed. RESULTS:Fifty patients were included in this study. In the longitudinal analysis, there were no differences in the levels of any of the markers immediately prior to and following the onset of delirium, but overall, median levels of adiponectin (9019 (IQR 5776-15,442) vs. 6148 (IQR 4447-8742) ng/ml, p?=?0.05) were significantly higher in patients with delirium compared to patients without delirium. In the cross-sectional analysis, median levels of the brain protein Tau (90 (IQR 46-224) vs. 31 (IQR 31-52) pg/ml, p?=?0.009) and the ratio Tau/amyloid ?1-42 (1.42 ((IQR 0.9-2.57) vs. 0.68 (IQR 0.54-0.96), p?=?0.003) were significantly higher in patients with hypoactive delirium compared to patients without. Levels of neopterin (111 (IQR 37-111) vs. 29 (IQR 16-64) mmol/l, p?=?0.004) and IL-10 (28 (IQR 12-39) vs. 9 (IQR 4-12) pg/ml, p?=?0.001) were significantly higher in patients with hypoactive delirium compared to patients with mixed-type delirium. CONCLUSIONS:While there are differences in markers (adiponectin and several brain proteins) between patients with and without delirium, the development of delirium is not preceded by a change in the biomarker profile of inflammatory markers or brain proteins. Patients with hypoactive delirium account for the observed differences in biomarkers. TRIAL REGISTRATION:ClinicalTrials.gov, NCT 01274819 . Registered on 12 January 2011.
| S-EPMC5970442 | biostudies-literature
Project description:BACKGROUND:Whereas ICU-acquired weakness may delay extubation in mechanically ventilated patients, its influence on extubation failure is poorly known. This study aimed at assessing the role of ICU-acquired weakness on extubation failure and the relation between limb weakness and cough strength. METHODS:A secondary analysis of two previous prospective studies including patients at high risk of reintubation after a planned extubation, i.e., age greater than 65?years, with underlying cardiac or respiratory disease, or intubated for more than 7?days prior to extubation. Patients intubated less than 24?h and those with a do-not-reintubate order were not included. Limb and cough strength were assessed by a physiotherapist just before extubation. ICU-acquired weakness was clinically diagnosed as limb weakness defined as Medical Research Council (MRC) score?<?48 points and severe weakness as MRC sum-score?<?36. Cough strength was assessed using a semi-quantitative 5-Likert scale. Extubation failure was defined as reintubation or death within the first 7?days following extubation. RESULTS:Among 344 patients at high risk of reintubation, 16% experienced extubation failure (56/344). They had greater severity and lower MRC sum-score (41?±?16 vs. 49?±?13, p?<?0.001) and were more likely to have ineffective cough than the others. The prevalence of ICU-acquired weakness at the time of extubation was 38% (130/244). The extubation failure rate was 12% (25/214) in patients with no limb weakness vs. 18% (12/65) and 29% (19/65) in those with moderate and severe limb weakness, respectively (p?<?0.01). MRC sum-score and cough strength were weakly but significantly correlated (rho?=?0.28, p?<?.001). After multivariate logistic regression analyses, the lower the MRC sum-score the greater the risk of reintubation; severe limb weakness was independently associated with extubation failure, even after adjustment on cough strength and severity at admission. CONCLUSION:ICU-acquired weakness was diagnosed in 38% in this population of patients at high risk at the time of extubation and was independently associated with extubation failure in the ICU.
| S-EPMC7069045 | biostudies-literature
Project description:BackgroundMitochondrial damage occurs in the acute phase of critical illness, followed by activation of mitochondrial biogenesis in survivors. It has been hypothesized that bioenergetics failure of skeletal muscle may contribute to the development of ICU-acquired weakness. The aim of the present study was to determine whether mitochondrial dysfunction persists until protracted phase of critical illness.MethodsIn this single-centre controlled-cohort ex vivo proof-of-concept pilot study, we obtained vastus lateralis biopsies from ventilated patients with ICU-acquired weakness (n = 8) and from age and sex-matched metabolically healthy controls (n = 8). Mitochondrial functional indices were measured in cytosolic context by high-resolution respirometry in tissue homogenates, activities of respiratory complexes by spectrophotometry and individual functional capacities were correlated with concentrations of electron transport chain key subunits from respiratory complexes II, III, IV and V measured by western blot.ResultsThe ability of aerobic ATP synthesis (OXPHOS) was reduced to ~54% in ICU patients (p<0.01), in correlation with the depletion of complexes III (~38% of control, p = 0.02) and IV (~26% of controls, p<0.01) and without signs of mitochondrial uncoupling. When mitochondrial functional indices were adjusted to citrate synthase activity, OXPHOS and the activity of complexes I and IV were not different, whilst the activities of complexes II and III were increased in ICU patients 3-fold (p<0.01) respectively 2-fold (p<0.01).ConclusionsCompared to healthy controls, in ICU patients we have demonstrated a ~50% reduction of the ability of skeletal muscle to synthetize ATP in mitochondria. We found a depletion of complex III and IV concentrations and relative increases in functional capacities of complex II and glycerol-3-phosphate dehydrogenase/complex III.
| S-EPMC4699339 | biostudies-literature
Project description:RationaleThe molecular mechanisms underlying the muscle atrophy of intensive care unit-acquired weakness (ICUAW) are poorly understood. We hypothesised that increased circulating and muscle growth and differentiation factor-15 (GDF-15) causes atrophy in ICUAW by changing expression of key microRNAs.ObjectivesTo investigate GDF-15 and microRNA expression in patients with ICUAW and to elucidate possible mechanisms by which they cause muscle atrophy in vivo and in vitro.MethodsIn an observational study, 20 patients with ICUAW and seven elective surgical patients (controls) underwent rectus femoris muscle biopsy and blood sampling. mRNA and microRNA expression of target genes were examined in muscle specimens and GDF-15 protein concentration quantified in plasma. The effects of GDF-15 on C2C12 myotubes in vitro were examined.Measurements and main resultsCompared with controls, GDF-15 protein was elevated in plasma (median 7239 vs 2454 pg/mL, p=0.001) and GDF-15 mRNA in the muscle (median twofold increase p=0.006) of patients with ICUAW. The expression of microRNAs involved in muscle homeostasis was significantly lower in the muscle of patients with ICUAW. GDF-15 treatment of C2C12 myotubes significantly elevated expression of muscle atrophy-related genes and down-regulated the expression of muscle microRNAs. miR-181a suppressed transforming growth factor-β (TGF-β) responses in C2C12 cells, suggesting increased sensitivity to TGF-β in ICUAW muscle. Consistent with this suggestion, nuclear phospho-small mothers against decapentaplegic (SMAD) 2/3 was increased in ICUAW muscle.ConclusionsGDF-15 may increase sensitivity to TGF-β signalling by suppressing the expression of muscle microRNAs, thereby promoting muscle atrophy in ICUAW. This study identifies both GDF-15 and associated microRNA as potential therapeutic targets.
| S-EPMC4345798 | biostudies-literature