Intensive care unit (ICU)-acquired weakness is a frequent complication of critical illness. It is unclear whether it is a marker or mediator of poor outcomes.
To determine acute outcomes, 1-year ...mortality, and costs of ICU-acquired weakness among long-stay (≥8 d) ICU patients and to assess the impact of recovery of weakness at ICU discharge.
Data were prospectively collected during a randomized controlled trial. Impact of weakness on outcomes and costs was analyzed with a one-to-one propensity-score-matching for baseline characteristics, illness severity, and risk factor exposure before assessment. Among weak patients, impact of persistent weakness at ICU discharge on risk of death after 1 year was examined with multivariable Cox proportional hazards analysis.
A total of 78.6% were admitted to the surgical ICU; 227 of 415 (55%) long-stay assessable ICU patients were weak; 122 weak patients were matched to 122 not-weak patients. As compared with matched not-weak patients, weak patients had a lower likelihood for live weaning from mechanical ventilation (hazard ratio HR, 0.709 0.549-0.888; P = 0.009), live ICU (HR, 0.698 0.553-0.861; P = 0.008) and hospital discharge (HR, 0.680 0.514-0.871; P = 0.007). In-hospital costs per patient (+30.5%, +5,443 Euro per patient; P = 0.04) and 1-year mortality (30.6% vs. 17.2%; P = 0.015) were also higher. The 105 of 227 (46%) weak patients not matchable to not-weak patients had even worse prognosis and higher costs. The 1-year risk of death was further increased if weakness persisted and was more severe as compared with recovery of weakness at ICU discharge (P < 0.001).
After careful matching the data suggest that ICU-acquired weakness worsens acute morbidity and increases healthcare-related costs and 1-year mortality. Persistence and severity of weakness at ICU discharge further increased 1-year mortality. Clinical trial registered with www.clinicaltrials.gov (NCT 00512122).
Estimators of glomerular filtration rate (GFR) have been shown to be flawed in critically ill patients, especially for augmented renal clearance (ARC), commonly defined as a measured urinary ...creatinine clearance (CrCl) ≥ 130 ml/min/1.73 m2 1. ...measuring CrCl should be performed in daily practice on the intensive care unit (ICU). ...the aim of this study is to define the most precise GFR estimator, which can then be used to detect ARC when measured CrCl is unavailable. ...the performance of these cut-offs was evaluated in an external single-center (Leuven, January 2016–December 2016) validation set by receiver-operating characteristics (ROC) curve analysis, using 2000 bootstrap replicates.
Purpose
To provide evidence-based guidelines for early enteral nutrition (EEN) during critical illness.
Methods
We aimed to compare EEN vs. early parenteral nutrition (PN) and vs. delayed EN. We ...defined “early” EN as EN started within 48 h independent of type or amount. We listed, a priori, conditions in which EN is often delayed, and performed systematic reviews in 24 such subtopics. If sufficient evidence was available, we performed meta-analyses; if not, we qualitatively summarized the evidence and based our recommendations on expert opinion. We used the GRADE approach for guideline development. The final recommendations were compiled via Delphi rounds.
Results
We formulated 17 recommendations favouring initiation of EEN and seven recommendations favouring delaying EN. We performed five meta-analyses: in unselected critically ill patients, and specifically in traumatic brain injury, severe acute pancreatitis, gastrointestinal (GI) surgery and abdominal trauma. EEN reduced infectious complications in unselected critically ill patients, in patients with severe acute pancreatitis, and after GI surgery. We did not detect any evidence of superiority for early PN or delayed EN over EEN. All recommendations are weak because of the low quality of evidence, with several based only on expert opinion.
Conclusions
We suggest using EEN in the majority of critically ill under certain precautions. In the absence of evidence, we suggest delaying EN in critically ill patients with uncontrolled shock, uncontrolled hypoxaemia and acidosis, uncontrolled upper GI bleeding, gastric aspirate >500 ml/6 h, bowel ischaemia, bowel obstruction, abdominal compartment syndrome, and high-output fistula without distal feeding access.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This controlled, randomized, multicenter trial compared early initiation (<2 days) with late initiation (≥8 days) of parenteral nutrition in adults in the intensive care unit. Late initiation was ...associated with less morbidity and enhanced recovery.
Critical illness induces anorexia and the inability to eat normally, predisposing patients to serious nutritional deficits, muscle wasting, weakness, and delayed recovery. Whether artificial nutritional support improves the outcome for critically ill patients is unclear. The administration route, the time until the initiation of artificial nutrition, the number of calories, and the type of nutrients may be important.
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Enteral nutrition is associated with fewer complications than parenteral nutrition and is less expensive to administer.
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However, the use of enteral nutrition alone often does not achieve caloric targets.
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In addition, underfeeding is associated with weakness, infection,
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an increased duration . . .
Patients who are critically ill can develop so-called intensive-care unit acquired weakness, which delays rehabilitation. Reduced muscle mass, quality, or both might have a role. The Early Parenteral ...Nutrition Completing Enteral Nutrition in Adult Critically Ill Patients (EPaNIC) trial (registered with ClinicalTrials.gov, number NCT00512122) showed that tolerating macronutrient deficit for 1 week in intensive-care units (late parenteral nutrition PN) accelerated recovery compared with early PN. The role of weakness was unclear. Our aim was to assess whether late PN and early PN differentially affect muscle weakness and autophagic quality control of myofibres.
In this prospectively planned subanalysis of the EPaNIC trial, weakness (MRC sum score) was assessed in 600 awake, cooperative patients. Skeletal muscle biopsies, harvested from 122 patients 8 days after randomisation and from 20 matched healthy controls, were studied for autophagy and atrophy. We determined the significance of differences with Mann-Whitney U, Median, Kruskal-Wallis, or χ(2) (exact) tests, as appropriate.
With late PN, 105 (34%) of 305 patients had weakness on first assessment (median day 9 post-randomisation) compared with 127 (43%) of 295 patients given early PN (absolute difference -9%, 95% CI -16 to -1; p=0·030). Weakness recovered faster with late PN than with early PN (p=0·021). Myofibre cross-sectional area was less and density was lower in critically ill patients than in healthy controls, similarly with early PN and late PN. The LC3 (microtubule-associated protein light chain 3) II to LC3I ratio, related to autophagosome formation, was higher in patients given late PN than early PN (p=0·026), reaching values almost double those in the healthy control group (p=0·0016), and coinciding with less ubiquitin staining (p=0·019). A higher LC3II to LC3I ratio was independently associated with less weakness (p=0·047). Expression of mRNA encoding contractile myofibrillary proteins was lower and E3-ligase expression higher in muscle biopsies from patients than in control participants (p≤0·0006), but was unaffected by nutrition.
Tolerating a substantial macronutrient deficit early during critical illness did not affect muscle wasting, but allowed more efficient activation of autophagic quality control of myofibres and reduced weakness.
UZ Leuven, Research Foundation-Flanders, the Flemish Government, and the European Research Council.
Context: Hyper- and hypoglycemia are associated with increased mortality of critically ill patients, but whether this association is causal remains unclear. Early randomized-controlled studies ...compared insulin infusion targeting “age-normal” blood glucose levels, labeled intensive insulin therapy, with an approach that considered hyperglycemia as a beneficial adaptation. These studies found benefits with maintaining normoglycemia. A recent large multicenter study, NICE-SUGAR, compared a similar age-normal with an intermediate glucose target and found the intermediate target superior. These results require explanation.
Evidence Acquisition: All published randomized controlled studies on glucose control in ICU were reviewed. The methodological differences between the repeat studies, most specifically NICE-SUGAR, and the original proof-of-concept studies, were systematically analyzed.
Evidence Synthesis: There were important methodological differences, possibly explaining different outcomes. These comprised different target ranges for blood glucose in control and intervention groups, different routes for insulin administration and types of infusion-pumps, different sampling sites, and different accuracies of glucometers, as well as different nutritional strategies and varying levels of expertise.
Conclusions: These differences do not permit confident recommendations for a single optimal glucose target in variable ICU settings. Respecting the “primum non nocere” principle, it appears safe not to embark on targeting age-normal levels in ICUs that are not equipped to accurately and frequently measure blood glucose and have not acquired extensive experience with iv insulin administration using a customized guideline. A simple overall fall-back position could be to maintain blood glucose levels as close to normal as possible without evoking unacceptable fluctuations, hypoglycemia, and hypokalemia.
The goal of intensive insulin therapy for critically ill patients is to control blood glucose levels asclose to normal as possible, without evoking unacceptable glucose fluctuations, hypoglycemia, or hypokalemia.
Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been increasingly recognized in the critically ill over the past decade. The variety of definitions proposed has led ...to confusion and difficulty in comparing one study to another.
An international consensus group of critical care specialists convened at the second World Congress on Abdominal Compartment Syndrome to standardize definitions for IAH and ACS based upon the current understanding of the pathophysiology surrounding these two syndromes.
Prior to the conference the authors developed a blueprint for the various definitions, which was further refined both during and after the conference. The present article serves as the final report of the 2004 International ACS Consensus Definitions Conference and is endorsed by the World Society of Abdominal Compartment Syndrome (WSACS).
IAH is redefined as an intra-abdominal pressure (IAP) at or above 12 mmHg. ACS is redefined as an IAP above 20 mmHg with evidence of organ dysfunction/failure. ACS is further classified as either primary, secondary, or recurrent based upon the duration and cause of the IAH-induced organ failure. Standards for IAP monitoring are set forth to facilitate accuracy of IAP measurements from patient to patient.
State-of-the-art definitions for IAH and ACS are proposed based upon current medical evidence as well as expert opinion. The WSACS recommends that these definitions be used for future clinical and basic science research. Specific guidelines and recommendations for clinical management of patients with IAH/ACS are published in a separate review.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background. Empirical antifungal therapy is the standard treatment for persistent or relapsing antibiotic-resistant neutropenic fever. However, overtreatment resulting in increased toxicity and ...treatment-related cost is a major shortcoming of such therapy. We assessed the feasibility of a "preemptive" approach based on the incorporation of sensitive, noninvasive diagnostic tests for consecutive high-risk neutropenic patients who had received fluconazole prophylaxis while avoiding empirical therapy. Methods. A total of 136 treatment episodes for persons who were at risk of acquiring invasive fungal infection (IFI) were screened for the presence of galactomannan with an enzyme immunoassay. A diagnostic evaluation, which included thoracic computed tomography scanning (HRCT) and bronchoscopy with lavage, was performed on the basis of well-defined clinical, radiological, and microbiological criteria. Only seropositive patients and patients with a positive microbiological test result plus supportive radiological findings received liposomal amphotericin B. Results. Neutropenic fever developed in 117 episodes, of which at least 41 episodes (35%) satisfied existing criteria for empirical antifungal therapy. However, our protocol-driven preemptive approach reduced the rate of antifungal use for these episodes from 35% to 7.7% (a 78% reduction) and led to the early initiation of antifungal therapy in 10 episodes (7.3%) that were clinically not suspected of being IFI. No undetected cases of invasive aspergillosis were identified; 1 case of zygomycosis was missed. Breakthrough candidemia was diagnosed by conventional culture techniques and was treated successfully. With use of a preemptive approach, the 12-week survival rate for patients with IFI was 63.6% (it was 63.1% for those with invasive aspergillosis). Conclusion. Preemptive therapy based on enzyme immunoassay and HRCT reduced the exposure to expensive and potentially toxic drugs and offered effective antifungal control, but it failed to detect non-Aspergillus IFI.
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BFBNIB, NUK, PNG, UL, UM, UPUK
In two recent randomized controlled trials, withholding parenteral nutrition early in critical illness improved outcome as compared to early up-to-calculated-target nutrition, which may be explained ...by beneficial effects of fasting. Outside critical care, fasting-mimicking diets were found to maintain fasting-induced benefits while avoiding prolonged starvation. It is unclear whether critically ill patients can develop a fasting response after a short-term nutrient interruption. In this randomized crossover pilot study, we investigated whether 12-h nutrient interruption initiates a metabolic fasting response in prolonged critically ill patients. As a secondary objective, we studied the feasibility of monitoring autophagy in blood samples.
In a single-center study in 70 prolonged critically ill patients, 12-h up-to-calculated-target feeding was alternated with 12-h fasting on day 8 ± 1 in ICU, in random order. Blood samples were obtained at the start of the study, at the crossover point, and at the end of the 24-h study period. Primary endpoints were a fasting-induced increase in serum bilirubin and decrease in insulin requirements to maintain normoglycemia. Secondary outcomes included serum insulin-like growth factor I (IGF-I), serum urea, plasma beta-hydroxybutyrate (BOH), and mRNA and protein markers of autophagy in whole blood and isolated white blood cells. To obtain a healthy reference, mRNA and protein markers of autophagy were assessed in whole blood and isolated white blood cells of 23 matched healthy subjects in fed and fasted conditions. Data were analyzed using repeated-measures ANOVA, Fisher's exact test, or Mann-Whitney U test, as appropriate.
A 12-h nutrient interruption significantly increased serum bilirubin and BOH and decreased insulin requirements and serum IGF-I (all p ≤ 0.001). Urea was not affected. BOH was already increased from 4 h fasting onwards. Autophagic markers in blood samples were largely unaffected by fasting in patients and healthy subjects.
A 12-h nutrient interruption initiated a metabolic fasting response in prolonged critically ill patients, which opens perspectives for the development of a fasting-mimicking diet. Blood samples may not be a good readout of autophagy at the tissue level.
ISRCTN, ISRCTN98404761. Registered 3 May 2017.
Critical illness polyneuropathy/myopathy causes limb and respiratory muscle weakness, prolongs mechanical ventilation, and extends hospitalization of intensive care patients. Besides controlling risk ...factors, no specific prevention or treatment exists. Recently, intensive insulin therapy prevented critical illness polyneuropathy in a surgical intensive care unit.
To investigate the impact of intensive insulin therapy on polyneuropathy/myopathy and treatment with prolonged mechanical ventilation in medical patients in the intensive care unit for at least 7 days.
This was a prospectively planned subanalysis of a randomized controlled trial evaluating the effect of intensive insulin versus conventional therapy on morbidity and mortality in critically ill medical patients. All patients who were still in intensive care on Day 7 were screened weekly by electroneuromyography. The effect of intensive insulin therapy on critical illness polyneuropathy/myopathy and the relationship with duration of mechanical ventilation were assessed.
Independent of risk factors, intensive insulin therapy reduced incidence of critical illness polyneuropathy/myopathy (107/212 50.5% to 81/208 38.9%, p = 0.02). Treatment with prolonged (> or = 14 d) mechanical ventilation was reduced from 99 of 212 (46.7%) to 72 of 208 (34.6%) (p = 0.01). This was statistically only partially explained by prevention of critical illness polyneuropathy/myopathy.
In a subset of medical patients in the intensive care unit for at least 7 days, enrolled in a randomized controlled trial of intensive insulin therapy, those assigned to intensive insulin therapy had a reduced incidence of critical illness polyneuropathy/myopathy and were treated with prolonged mechanical ventilation less frequently.
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